Abstracta 2003: Mehrkens KA, Kayhan N, Ell N, Schuppe A, Hagl S, Vahl CF (2003): Einfluss akuter Ethanolexposition am isolierten humanen Myokard Z Herz-, Thorax-, Gefäßchir. Dez; 17(6): 247-256 Zusammenfassung: Ziel: Paroxysmales Vorhofflimmern kann klinisch mit chronischem Alkoholabusus assoziiert sein. Massiver Alkoholkonsum von Nicht-Alkoholikern kann unmittelbar zu intermittierendem Vorhofflimmern führen (Holiday Heart Syndrome). Die pathophysiologische Ursachenkette von Alkoholkonsum und akuter atrialer Rhythmusstörung ist jedoch bisher nicht detailliert untersucht. Die vorliegende Untersuchung hat zum Ziel die Auswirkungen akuter Ethanolexposition auf das Kontraktionsverhalten und den intrazellulären Calciumstoffwechsel am Modell der intakten (schlagenden) menschlichen Herzmuskelfaser sowie auf der Ebene des isolierten kontraktilen Apparates (geskinnten Herzmuskelfasern) am rechtsatrialen Myokard von 27 Patienten, die sich einer aorto-coronaren Bypass-Operation unterzogen, systematisch zu untersuchen. Methode: A) Intraoperativ exzidierte intakte rechtsatriale Trabekel (0,3 × 4,0 mm, n = 6) wurden mit FURA-2/AM inkubiert, in eine Messeinrichtung eingebracht, auf optimale Länge vorgedehnt und elektrisch stimuliert (Messbedingungen: 37 °C; oxygenierte Krebs-Henseleit- Lösung; supramaximale elektrische Stimulation). Intrazelluläre Calciumtransienten und Ausmaß der Kraftentwicklung wurden als Funktion der Ethanolkonzentration (0–32) analysiert. B) Mittels Triton-X-100 demembranisierte Herzmuskelfasern (0,05 × 3,0 mm) wurden tonisch aktiviert und das Kontraktionsverhalten in Abhängigkeit der Ethanolkonzentration (0–100) analysiert. Ergebnisse: A) Bei steigenden Ethanolkonzentrationen zeigte sich am intakten Muskelpräparat eine signifikante Reduktion der isometrisch entwickelten Kraft (p < 0,001), des intrazellulären Calciumtransienten und des systolischen Calciumpeaks (p < 0,01). In der Diastole blieben Kraftentwicklung und Calciumtransient unbeeinflusst. B) Steigende Ethanolkonzentrationen verursachten im geskinnten Muskelpräparat eine signifikante Reduktion der Kraftentwicklung (p < 0,01). Diese Auswirkungen waren in beiden Gruppen A und B reversibel. Schlussfolgerung: Die Daten belegen, dass Ethanol einen direkten Einfluss auf den Calciumhaushalt, einhergehend mit einer Kontraktilitätseinbuße des Myokards, hat. Bei höheren Ethanolkonzentrationen kommt es zu einem direkten Einfluss auf der Ebene des kontraktilen Apparates. Beide Effekte könnten das Auftreten des paroxysmalen Vorhofflimmerns nach exzessivem Ethanolgenuss begünstigen. Behrens L, Reinerth G, Albers J, Hagl S, Dössel O, Vahl CF (2003): 4D-Visualisierung der elektrischen Erregungsausbreitung am isoliert schlagenden Schweineherzen. Z Herz-, Thorax-, Gefäßchir 17: 73-83 Abstract: Fragestellung: Kathetergestützte Mapping-Systeme sind heute in der Lage, simultan die Erregungsabläufe einer ganzen Herzkavität zu erfassen, um arrhythmogene Foki zu detektieren. Vorhofflimmern (VHF) ist die häufigste Rhythmusstörung, deren gezielte interventionell-kardiologische wie auch rhythmuschirurgische Therapie nach einer exakten Charakterisierung verlangt. Um die anatomische Genauigkeit des Mapping zu erhöhen, untersuchten wir die Möglichkeit, Mapping-Bilder mit simultan gewonnenen drei- und vierdimensionalen computertomographischen (CT) Aufnahmen zu kombinieren. Methoden 20 isolierte Schweineherzen wurden am modifizierten Langendorff-Apparat reperfundiert. Mit einem Subsekunden-Spiral-Computertomographen wurden Schnittbilder angefertigt, die nach Segmentierung bis in die vierte Dimension (Zeit) rekonstruiert wurden, wobei mittels retrospektivem EKG-Gating eine zeitliche Auflösung von bis zu 50ms gelang. Simultan wurden die Erregungsabläufe in den Vorhöfen im Sinusrhythmus und bei VHF mit dem Non-Contact-Mapping-System EnSite 3000 abgeleitet. Ergebnisse: Rekonstruierte CT-Bilder und Mapping-Daten wurden zu drei- bis vierdimensionalen anatomischen Bildern der normalen und rhythmusgestörten atrialen Erregungsleitung kombiniert. Die Segmentierung des Herzens erfolgte durch interaktive Deformation von Dreiecksnetzen zu einem Zeitpunkt, dann durch elastisches Matching zu den übrigen Zeitpunkten. Eine Simulation der Erregungsausbreitung gelang mit Hilfe eines zellulären Automaten, dessen Arbeitsweise auf dem Prinzip der Erregungsausbreitung von Zelle zu Zelle bei definierbaren elektrophysiologisch relevanten Parametern beruht. Schlussfolgerung: Die Einbeziehung der Computertomographie als bildgebendes Verfahren ist im Vergleich zu bisherigen Einsätzen des endokardialen Mapping das wesentliche neue Merkmal unserer Methode. Sie ermöglicht es dem Untersucher insbesondere, den Ursprungsort und die Ausbreitung von Arrhythmien anatomischen Strukturen des jeweiligen Herzens zuzuordnen. Das von uns vorgestellte kombinierte bildgebende Verfahren aus endokardialem Mapping und Computertomographie stellt ein neues Hilfsmittel für die experimentelle Erforschung, präoperative Diagnostik sowie Simulation und die damit verbundene Behandlung von Herzrhythmusstörungen dar. 2002: Buhmann V, Hackert T, Sebening C, Szabó G, Vahl CF, Hagl S (2002): Hämodynamische Instabilität nach Hirntod I: Auswirkungen der veränderlichen Nachlast. Z Herz-, Thorax-, Gefäßchir 16: 79-85 Abstract: Fragestellung: Welche Bedeutung haben die veränderten Lastbedingungen im Hinblick auf die hämodynamische Instabilität und die kardiale Funktionseinschränkung im hirntoten Organspender. Methoden: Der Hirntod wurde durch Füllung eines subduralen Ballonkatheters eingeleitet. Linksventrikuläre Druck-Volumen-Kurven wurden mit Hilfe eines Conductance-Druck-Katheters aufgenommen und daraus die Steigung der end-systolischen Druck-Volumen-Beziehung (Ees), die arterielle Elastizität (Ea), die Schlagarbeit (SW), die Druck-Volumen-Fläche (PVA), die ventrikulo-arterielle Kopplung (VAC) und die mechanische Effektivität (Eff) berechnet. Ergebnisse: Die Hirntodinduktion führte zu einer hyperdynamen Antwort mit einem signifikanten Anstieg der meisten hämodynamischen Parameter. Nach 4 Stunden zeigten die hämodynamischen Parameter einen signifikanten Abfall im Vergleich zu den Ausgangswerten (Ees: 4,07±0,51 vs. 8,06±1,09 mmHg/ml, P<0,05; Ea: 3,17±0,39 vs. 4,42±0,30 mmHg/ml, P<0,05). Während VAC (0,78±0,09 vs. 0,65±0,14 n.s.) und Eff (73,4±2,1% vs. 76,8±3,7% n.s.) über den gesamten Beobachtungszeitraum konstant blieben. Schlussfolgerung: Die akute intrakranielle Druckerhöhung führt zu einer initialen hyperdynamen Reaktion gefolgt von einer hämodynamischen Instabilität. Die unveränderte ventrikulo-arterielle Kopplung und mechanische Effektivität lassen vermuten, dass die eingeschränkte Kontraktilität nach Hirntod durch die gleichzeitig verringerte Nachlast verursacht wird. Buhmann V, Hackert T, Sebening C, Vahl CF, Hagl S, Szabó G (2002): Hämodynamische Instabilität nach Hirntod II: Koronarzirkulation und Endothelfunktion. Z Herz-, Thorax-, Gefäßchir 16: 86-91 Abstract: Einleitung: Es wurde bereits in mehreren Studien über die endotheliale Dysfunktion nach Herztransplantation berichtet. Sie scheint eine wichtige Rolle bei der Entstehung von Reperfusionsschäden und Abstoßungsreaktionen zu spielen. Bisher bleibt allerdings unklar welchen Einfluss der Hirntod auf diese Phänomene hat. In der vorliegenden Arbeit wurden deshalb die Auswirkungen des Hirntodes auf die Koronarzirkulation und die Endothelfunktion untersucht. Material und Methoden: Durch die Füllung eines subdural gelegenen Ballonkatheters wurde der Hirntod bei 6 Hunden eingeleitet. Über einen Conductance-Katheter wurden die linksventrikulären Druck- und Volumenwerte registriert. Zusätzlich erfolgte eine kontinuierliche Aufnahme des koronaren Blutfußes (CBF) im R. interventricularis ant. (LAD) und im R. circumflexus (LCX) der linken Koronararterie. Jeweils vor und 3Stunden nach Hirntodinduktion wurden die endothelabhängige Vasodilatation nach Gabe von Acetylcholin und die endothelunabhängige Vasodilatation nach Gabe von Natriumnitroprussid gemessen. Ergebnisse: Die akute intrakranielle Druckerhöhung führte initial zu einer hyperdynamen Reaktion mit einem signifikanten (P<0,05) Anstieg von CBF und myokardialer Kontraktilität. Nach 3 Stunden zeigten der mittlere aortale Druck, die myokardiale Kontraktilität, CBF-LAD (26,8±4,8 vs. 38,2±3,4 ml/min) und CBF-LCX (47,2±8,2 vs. 63,4±5,5 ml/min) einen signifikanten (P<0,05) Abfall unter die Ausgangswerte. Während die Gabe von Acetylcholin vor Hirntodinduktion zu einer monophasischen Vasodilatation (LAD: +61±8%, LCX: +52±6%) führte, kam es 3Stunden nach Hirntodinduktion nur zu einer leichten Vasodilatation (LAD: +19±5%, LCX: +23±4%, P<0,05) gefolgt von einer längeren Vasokonstriktion (LAD: -38±6%, LCX: -40±5%, P<0,001). Die endothelunabhängige Reaktion zeigte keine Unterschiede. Schlussfolgerungen: Der Hirntod hat wichtige Auswirkungen auf die Koronararterienzirkulation. Erstens führt der parallel zum Abfall der Nachlast ebenfalls verringerte CBF zu einer hämodynamischen Instabilität und zweitens entsteht eine schwere endotheliale Dysfunktion, die entscheidende Auswirkungen auf den Zustand nach Transplantation haben könnte. Doll M, Kayhan N, Vahl CF, Hagl S (2002): Kontraktionsverhalten des isolierten Kardiomyozyten: Einfluss von Interleukin-1 und Interleukin-6. Z Herz-,Thorax-, Gefäßchir 16: 10-20 Abstract: Fragestellung: Interleukin-1 (IL-1) und Interleukin-6 (IL-6) spielen bei septischen Krankheitsbildern, der extrakorporalen Zirkulation, sowie beim Myokardinfarkt womöglich eine entscheidende Rolle. In dieser Studie wurde dieser Einfluss von Interleukin-1 und Interleukin-6 auf das Kontraktionsverhalten und den intrazellulären Calciumtransienten des isolierten Kardiomyozyten analysiert. Als Modell wurde der isolierte Kardiomyozyt als kleinste kontraktile Einheit gewählt, da hiermit der direkte Effekt der Interleukine ohne Einflussnahme modulierender Faktoren, wie Endothel und Bindegewebe, untersucht werden konnte. Methoden: Kardiomyozyten aus ventrikulärem Myokard der Ratte (n=6) wurden mit Kollagenasen isoliert, mit dem Fluoreszenzfarbstoff FURA-2 für die Messung des intrazellulären Calciumtransienten beladen und elektrisch stimuliert (0,5 Hz, 37°C, Krebs-Henseleit, pH 7,4). Ergebnisse: Mit zunehmenden Interleukinkonzentrationen kommt es zu einer dosisabhängigen und signifikanten Abnahme der Verkürzungsamplitude (IL-1: p<0,01; IL-6: p<0,01) und der Kontraktionsgeschwindigkeit (IL-1: p<0,01; IL-6: p<0,01) sowie des intrazellulären Calciumtransienten (IL-1: p<0,01; IL-6: p<0,01). Interleukin-6-induzierte Veränderungen waren reversibel. Für die durch Interleukin-1 verursachten Alterationen hingegen konnte keine Reversibilität gezeigt werden. Schlussfolgerung: Erhöhte Spiegel von Interleukin-1 und Interleukin-6 können eine Ursache für Störungen des Kontraktionsverhaltens und des intrazellulären Calciumstoffwechsels sein. Die Befunde lassen vermuten, dass erhöhte Konzentrationen dieser Mediatoren unter den Bedingungen einer septischen Stoffwechsellage, der extrakorporalen Zirkulation, sowie beim Myokardinfarkt eine negativ inotrope Wirkung haben und an der unter klinischen Bedingungen beobachteten Einschränkung der ventrikulären Pumpfunktion wesentlich beteiligt sind. Gleissner CA, Zehelein J, Sack FU, Schnabel P, Haass M, Dengler TJ. (2002): Extended experience and subgroup analysis using cardiac troponin T for rejection monitoring after heart transplantation. Transplant Proc 34(6): 2178-2180 Abstract: Cardiac Troponin T (cTnT) is a cardio-specific myofibrillar protein. Detection of cTnT in the circulation might allow noninvasive rejection diagnosis after heart transplantation, as it is released from injured or necrotic cardiomyocytes. [1] The objective of this study was to evaluate cTnT determination for rejection monitoring after heart transplantation. Kayhan N, Bodem J, Vahl C, Hagl S (2002): The positive staircase (force-frequency relationship) and the Frank-Starling mechanism are altered in atrial myocardium of patients in end-stage heart failure transplanted for dilative cardiomyopathy. Transplant Proc 34: 2185-2191 Abstract: The classic implantation technique for donor hearts utilizes anastomoses of the aorta, the pulmonary artery, and the left and right atrium. The importance of atrial myocardium in heart transplantation is due to the fact that large parts of the recipient left and right atrium remain in situ, providing a site to suture donor and recipient atria. However, while the status of the ventricular myocardium in end-stage failing hearts is well characterized, little is known about atrial pathophysiology. If one supposes that the recipient atrial myocardium is severely altered, it seems reasonable to hypothesize that potential pathophysiological alterations may affect the new donor organ when donor and recipient myocardium are connected by an atrial suture line. In an attempt to characterize contractile function in more detail, the atrial Frank-Starling mechanism and the atrial force-frequency relationship were analyzed in donor and recipient hearts using atrial trabeculae. The Frank-Starling mechanism states that an increase in diastolic filling causes an increase in peak systolic atrial pressure. The force-frequency relationship (or "staircase phenomenon'') describes an increase in force output upon increasing stimulation frequencies up to an optimal level. Controversal results have been reported regarding the applicability of the Frank-Starling mechanism in failing human ventricular myocardium. While Böhm et al[1] and Schwinger et al [2] found that the Frank-Starling mechanism is absent in failing human ventricular myocardium, Holubarsch et al [3] and Vahl et al [4] could not reproduce this observation. An increase in heart rate will increase force production by increasing intracellular calcium.[5 and 6] However, under pathological conditions these processes are impaired in ventricular myocardium. [7] The present study analyzes the Frank-Starling mechanism and the force-frequency relationship in atrial human donor and recipient myocardium obtained during heart transplantation. 2001: Albers J, Vahl CF, Haßfeld S (2001): Querschnittsprojekt Q2: Methodenevaluierung Proceedings: Rechner- und sensorgestützte Chirurgie: 203-216 Abstract: Die mehrdimensionale Untersuchung von Patienten, die an Herzklappeninsuffizienzen (undichten Herzklappen) leiden, stellt eine wesentliche Innovation in der Indikationsstellung, Planung und Verlaufskontrolle dar. Während früher zweidimensionale Angiographie- und Dopplerverfahren lediglich eine Semiquantitation der Rückflussvolumina (Jets) zuließen, gestattet die dreidimensionale Quantifizierung mittels 3D-Echo eine weitaus präzisere Diagnostik. Insbesondere eröffnete das neue Verfahren den Blick auf die zugrundeliegenden Pathologien: So führen verschiedene Mitralklappenschädigungsmuster zu korrespondierenden Jetgeometrien. Als weitere Möglichkeit zur volumetrischen Bestimmung von Regurgitationsjets kommt die Magnetresonanztomographie in Frage. Hierbei können Flussgeschwindigkeits-Informationen winkelunabhängig und ohne notwendige Erreichbarkeit geeigneter Schallfenster erhoben werden. Alternative volumetrische Verfahren (Computertomographie, EBCT, Angiographie, Szintigraphie) verwenden Kontrastmittel oder sind auf geometrische Annahmen angewiesen, um aus 2D-Daten mehrdimensionale Informationen zu schätzen. Das Ziel dieses Teilprojekts war eine Methodenentwicklung zur experimentellen Evaluierung der beiden klinisch relevanten Verfahren 3D-Echokardiographie und Magnetresonanztomographie zur volumetrischen Bestimmung und zur qualitativen Darstellbarkeit von Herzklappen-Insuffizienzjets. Kayhan N, Krempien R, Wannenmacher M, Vahl CF (2001): Rechnergestützte chirurgische Rekonstruktion von Herzkranzgefäßen: Hightech-Lösung für ein kinisches Problem. Proceedings: Rechner- und sensorgestützte Chirurgie: 323-332 Abstract: end stage coronary artery disease with linear stenosis of the main vessels despite several coronary interventions (including stent implantation) is a current challenge for surgical treatment. As the long term results are mainly determined by the pathology of the coronary vessels a simple revascularisation with arterial or venous grafts provides no adequate solution of the problem. An exactly controlled 3D-reconstruction of the coronary vessels including selective thrombendarteriectomy (TEA) seems to be a new approach that may be limited by early neo-intima-proliferation of the coronary vessels. Intraoperativ brachytherapy may be a tool to inhibit (or control) this process. Scientists of different disciplines have begun to develop a tool, that will provide a surgical solution of this problem, that is embedded in a high-tech enviroment. Kewitz S, deBoer I, Schöls W, Werner C, Dössel O, Vahl CF (2001): Elektromechanische Modellierung des Vorhofs: Validierung, Planung und Simulation atrialer rhythmuschirurgischer Eingriffe. Proceedings: Rechner- und sensorgestützte Chirurgie: 306-314 Abstract: Anatomische, elektrophysiologische und elastomechanische Modelle des Atriums zur Planung rhythmuschirurgischer Eingriffe werden vorgestellt. Die Modelle beruhen einerseits auf publizierten mathematischen Beschreibungen der Elektrophysiologie und Mechanik, anderseits auf Messdaten, welche mittels Tierexperimente gewonnenen wurden. Die Messdaten wurden für die Erstellung anatomischer und elektrophysiologischer Modelle herangezogen, sowie mit Simulationsergebnissen verglichen. Naujokat E, Kiencke U, Vahl CF (2001): Ein Beobachtersystem zur Patientenüberwachung in der Herzchirurgie. Proceedings: Rechner- und sensorgestützte Chirurgie: 289-297 Abstract: Die meisten Eingriffe in der Herzchirurgie erfordern ein stillgelegtes, blutleeres Herz und werden heute unter extrakorporaler Zirkulation (EKZ) durchgeführt. Bei dieser Operationstechnik wird die Kreislauffunktion künstlich mit Hilfe einer Herz-Lungen-Maschine (HLM) aufrechterhalten. Die Regelung der HLM erfolgt durch den Kardiotechniker auf der Basis seiner klinischen Erfahrung sowie prä- und intraoperativ erhobener Messdaten. Allerdings sind während EKZ viele wichtige Kreislaufparameter unbekannt, da für Meßsonden unzugänglich, wie z.B. die Perfusion von Gehirn, Nieren, Leber und Darm. Andere wichtige Patientenparameter wie z. B. Blutgaswerte oder pH werden nur diskontinuierlich (alle 15-30 Minuten) gemessen, da die Messmethoden (Blutanalyse im Labor) sehr aufwendig sind. Ein Beobachtersystem, das derartige Patientenparameter kontinuierlich intraoperativ schätzt, kann die Informationsbasis für die Entscheidungen des Kardiotechnikers zur Regelung der HLM erweitern und somit dazu beitragen, dieses Operationsverfahren möglichst gut auf den aktuellen Patientenzustand abzustimmen und damit möglichst schonend für den Patienten zu gestalten. Das hier vorgestellte Beobachtersystem basiert auf einem Computer-Modell des menschlichen Kreislaufs. Dieses Modell bildet den arteriellen Körperkreislauf sehr detailliert mit Hilfe von 128 Segmenten ab. Jedes dieser Segmente entspricht einem Gefäßabschnitt und wird durch dessen physikalische Eigenschaften Länge, Radius, Wanddicke und Elastizität charakterisiert. Die Segmente sind untereinander entsprechend der anatomischen Architektur des arteriellen Körperkreislaufs verschaltet. Blutfluss und -druck in den einzelnen Segmenten werden mit Hilfe von Differentialgleichungen berechnet, die auf die Navier-Stokes-Gleichungen für Flüssigkeitsströmungen in elastischen Gefäßen zurückgehen. Dieses detaillierte Modell ist in der Lage, die Pulsatilität des arteriellen Kreislaufsystems nachzubilden und bietet darüber hinaus den Vorteil einer hohen Auflösung von Blutdruck und -fluss sowohl bezüglich der Zeit als auch bezüglich des Ortes innerhalb des arteriellen Körperkreislaufs. Szabó G, Kiencke U, Hagl S, Vahl CF (2001): Veno-atrio-ventrikuläre Kopplung: Modellierung der Mitralklappenfunktion. Proceedings: Rechner- und sensorgestüzte Chirurgie: 315-322 Abstract: In der vorliegenden Studie wurden die Auswirkungen experimentell induzierter akuter Veränderungen der Vorlast und des Füllungmusters der Ventrikel unter physiologischen und pathophysiologischen Bedingungen analysiert. Die Untersuchungen fokusierten auf die Mitralinsuffizienz und den Mitralklappenersatz. In unsrerer Studie ist es erstmals gelungen, die atrio-ventrikulären hämodynamischen Veränderungen während der Füllungsphase realitätsnah in einem „lumped parameter“ Modell darzustellen. Darüber hinaus weisen die Daten daraufhin, dass Patienten mit Mitralvitien nicht nur von der Wiederherstellung der Ventilfunktion (Mitralklappenersatz/Plastik) sondern auch von der Korrektur der Ventrikelgeometrie profitieren könnten. 1998: Bauernschmitt R, Bohrer H, Hagl S (1998): Rescue therapy with C1-esterase inhibitor concentrate after emergency coronary surgery for failed PTCA Intensive Care Med. 1998 Jun; 24(6): 635-8 Abstract:Administration of C1-esterase inhibitor (C1-INH) attenuates myocardial necrosis and sustains normal cardiac performance after myocardial ischemia and reperfusion in animal experiments. We report on our first experience of C1-INH application as rescue therapy in patients undergoing emergency surgical revascularization after failed percutaneous transluminal coronary angioplasty. Three patients were treated, because post-operative hemodynamic stabilization could not be achieved despite prolonged reperfusion periods, high-dose inotropic support, inodilators and aortic counterpulsation. As there was no surgical or medical option remaining, C1-INH was administered starting with a 2000 unit bolus, followed by 1000 U 12 and 24 h after surgery. C1-INH therapy resulted in rapid hemodynamic stabilization of all patients; weaning from aortic counterpulsation and epinephrine support was possible within 1 day. All patients survived and were discharged from hospital. In this group of patients suffering from severe reperfusion injury after coronary surgery, C1-INH seemed to be an effective adjuvant therapy to restore myocardial function by blocking the complement cascade. These results should encourage the performance of controlled studies on the effects of prophylactic C1-INH substitution therapy in patients undergoing coronary surgery at high risk conditions. Bauernschmitt R, Jakob HG, Vahl CF, Lange R, Hagl S (1998): Operation for infective endocarditis: results after implantation of mechanical valves Ann Thorac Surg. 1998 Feb; 65(2): 359-64 Abstract: Operation for acute endocarditis during the active phase violates a basic surgical rule not to implant a foreign body into an infective process, resulting in a high operative mortality and the risk of early recurrent endocarditis. Several investigators analyzing risk factors for perioperative mortality and morbidity presented strategies for more favorable outcomes, but most studies suffer from the drawback of heterogeneous populations observed over a long period of time. METHODS: We present a prospective study on 138 patients operated on from March 1988 to March 1996. Patients were only included if the activity of the infection was proved by positive culture of the valve leaflets or by histologic staining. During the observation period, indication for operation, surgical approach, and postoperative antibiotic therapy were standardized as much as possible. After radical debridement of all parts of infected tissue, valve replacement was carried out with mechanical prostheses. RESULTS: The early mortality was 11.5% overall. High New York Heart Association functional classification, advanced age, and staphylococcal disease were significant risk factors for early mortality. The site of infection, multiple valve involvement, and prosthetic valve endocarditis did not affect the outcome. Early recurrent endocarditis was recorded in only 3 patients of the entire series. CONCLUSIONS: In case of acute infective endocarditis, valve replacement with mechanical prostheses is a safe procedure, if radical operation and aggressive postoperative antibiotic therapy are performed. For further improvements of the results, earlier operation is advisable in patients with rapidly progressive cardiac deterioration and in most cases of staphylococcal endocarditis. Bauernschmitt R, De Simone R, Lange R, Vahl CF, Thomas G, Hagl S (1998): [Surgery of acute aortic valve endocarditis: prognosis in paravalvular abscess] Z Kardiol. 1998 Apr; 87(4): 276-82 Abstract:The occurrence of paravalvular abscesses in the course of an acute endocarditis of the aortic valve indicates an advanced stadium of the disease. The infection has spread beyond the limits of the valve leaflets, and ongoing destruction of the paravalvular tissue is to be expected, if the endocarditis is continually treated by antibiotics alone. Surgery of acute endocarditis with paravalvular abscess, however, supposedly carries an increased risk of early mortality and late morbidity. The following prospective study was carried out to determine whether a radical surgical approach together with aggressive postoperative antibiotic therapy could help to improve results. Between 1988 and 1995, 138 patients were operated during the acute phase of infective endocarditis; in 102 the aortic valve was involved. Among these, 44 had paravalvular abscesses at the time of surgery. The mean age of both groups was the same, but there was a higher rate of concomitant coronary artery disease, multiple valve involvement, advanced NYHA-class, and staphylococcal disease among the patients with abscesses. All interventions were carried out with cardiopulmonary bypass and cardioplegic arrest. The aortic valve was resected, abscesses were removed, and each part of potentially infected or necrotic tissue was resected as complete as possible, irrespective of the possibility to jeopardize the conduction system or to create large tissue defects. The aortic valve was replaced with a mechanical prosthesis in each case. The postoperative antibiotic regimen was specifically directed against the microorganisms isolated preoperatively; therapy was only modified, if signs of systemic infection did not disappear three days after surgery. The operative mortality was 10% among patients without an abscess and 11% in patients with a paravalvular abscess. Early recurrent endocarditis was recorded in two patients without and in only one patient with an abscess. Late recurrent endocarditis was noted in three patients; none of them had abscesses at the time of surgery. We conclude that the operative risk of acute endocarditis of the aortic valve with a paravalvular abscess does not have to be inevitably higher compared to cases without paravalvular involvement. To achieve these results, it is necessary to use a radical surgical approach and to adjust postoperative antibiotic therapy, if infectious signs do not disappear shortly after surgery. Dengler TJ, Zimmermann R, Braun K, Muller-Bardorff M, Zehelein J, Sack FU, Schnabel PA, Kubler W, Katus HA (1998): Elevated serum concentrations of cardiac troponin T in acute allograft rejection after human heart transplantation J Am Coll Cardiol. 1998 Aug; 32(2): 405-12 Abstract: This study evaluates the concept and diagnostic efficacy of using serum troponin T for the detection of cardiac graft rejection. BACKGROUND: Cardiac troponin T is a cardiospecific myofibrillar protein, which is only detectable in the circulation after cardiac myocyte damage. It might be expected to be released during acute heart allograft rejection, allowing noninvasive rejection diagnosis. METHODS: In 35 control subjects and in 422 samples from 95 clinically unremarkable heart allograft recipients more than 3 months postoperatively, troponin T serum concentrations were compared to the histological grade of acute graft rejection in concurrent endomyocardial biopsies. RESULTS: Mean troponin T serum concentrations were identical in control subjects (23.2 +/- 1.4 ng/liter) and in heart transplant recipients without graft rejection (International Society for Heart and Lung Transplantation [ISHLT] grade 0; 22.4 +/- 1.7 ng/liter). Mean troponin T concentrations increased in parallel with the severity of graft rejection (ISHLT grade 1: 27.8 +/- 1.8 ng/liter; grade 2: 33.2 +/- 2.7 ng/liter; grade 3A: 54.6 +/- 6.5 ng/liter; grade 3B and 4: 105.4 +/- 53.7 ng/liter; p < 0.001 for grades 3 and 4 vs. grades 0 and 1). The proportion of positive samples also increased in parallel with rejection severity, reaching 100% in rejections of grade 3B and 4. Sensitivity and specificity for the detection of significant graft rejection (ISHLT grade 3/4) were 80.4% and 61.8%, respectively. The negative predictive value was most remarkable with 96.2%. Intraindividual longitudinal analysis of troponin T levels and biopsy results in 15 patients during long-term follow-up confirmed these findings. CONCLUSIONS: The present data demonstrate that acute allograft rejection after human heart transplantation is often associated with increased serum concentrations of troponin T. All cases of serious forms of graft rejection would have been detected before the development of clinical symptoms. Measurement of troponin T levels may become a useful ancillary parameter for noninvasive rejection diagnosis, being most valuable in the exclusion of severe cardiac graft rejection. Herold U, Jakob H, Kamler M, Thiele R, Tochtermann U, Weinmann J, Motsch J, Gebhard MM, Hagl S (1998): Interruption of bronchial circulation leads to a severe decrease in peribronchial oxygen tension in standard lung transplantation technique Eur J Cardiothorac Surg. 1998 Feb; 13(2): 176-83 Abstract: In clinical practice lung transplantation is the only procedure where the transplanted organ is left without its own arterial perfusion. With the interruption of the bronchial arteries the nutritive support is dependent on collateral flow by the pulmonary artery and the oxygen tension of desaturated central venous blood, representing an abnormal physiology. METHODS: To analyze this problem systematically, we used a standard single left lung transplantation model in the pig (n = 12). In accordance with the clinical standard, lung preservation was performed with modified Euro-Collins solution with addition of prostacycline. The duration of ischemia was set to 4 h. Before and after single left lung transplantation tissue oxygen tension in the peribronchial tissue was measured with Licox tissue pO2 microprobes. For validation, the myocardial tissue oxygen tension was recorded simultaneously. The hemodynamic assessment included continuous flow measurement of the left and right pulmonary artery using Transsonic ultrasound flow probes. After transplantation the animals were observed for 4 h. For hypothetic augmentation of collateral blood flow to the peribronchial tissue we administered Nitric oxide (10 ppm) to the ventilation in six pigs (group B). Six pigs (group A) served as a control without the addition of nitric oxide (NO). All pigs were ventilated with a FiO2 of 0.5 resulting in paO2 values between 160 and 200 mmHg. RESULTS: In both groups single lung transplantation led to a significant decrease in peribronchial tissue oxygen tension throughout the observation period. Pre-Tx values of peribronchial tissue oxygen tension (38.31 +/- 6.56 mmHg) decreased to 9.72 +/- 2.55 mmHg in group A and 10.3 +/- 3.61 mmHg in group B after 4 h, which could not be altered by a FiO2 of 1.0 (P < 0.0001). The addition of NO in group B led to a significantly augmented flow in the left pulmonary artery (0.63 +/- 0.31 l/min in group B vs. 0.46 +/- 0.26 l/min group A, P < 0.001) representing 67 vs. 49% of the pre-Tx flow in groups B and A, respectively, but the peribronchial tissue oxygen tension was not influenced (P > 0.05). In both groups A and B, the central venous pO2 did not differ in the postoperative period (41.83 +/- 3.27 mmHg group A vs. 43.26 +/- 2.98 mmHg group B) and was kept in a comparable range to the pretransplantation values (45.23 +/- 3.41 mmHg pre-Tx). CONCLUSIONS: The persistence of a very low peribronchial tissue oxygen tension in the early phase after lung transplantation cannot be influenced by improved pulmonary artery flow and solely relates to the central venous pO2, which cannot be augmented by the addition of NO. This mechanism might be a trigger for anastomotic healing problems, infectious complications and later development of obliterative bronchiolitis (OB). Mehmanesh H, Lange R, Hagl S (1998): Temporary atrial electrode for the treatment of supraventricular tachycardia after cardiac operations Ann Thorac Surg. 1998 Mar; 65(3): 632-6 Abstract: Supraventricular tachycardia is a common postoperative complication early after cardiac operations. A temporary atrial patch electrode for low energy atrial defibrillation was developed in 1992 and subsequently tested. METHODS: The electrode first was tested and removed intraoperatively during open heart operations in 10 patients (phase I). After the intraoperative testing, the temporary atrial patch electrode was implanted in 20 patients for postoperative termination of spontaneous episodes of supraventricular tachycardia (phase II). When supraventricular tachycardia occurred, biphasic shocks (1.2 to 5 J) were applied and the atrial defibrillation thresholds were measured. RESULTS: In phase I, the mean intraoperative atrial defibrillation threshold was 1.6 +/- 1.4 J, with a mean shock impedance of 64 +/- 7.3 omega. In phase II, 6 of 20 patients (30%) had 7 episodes of atrial fibrillation (n = 6) and atrial flutter (n = 1) after operation. In 5 patients, the supraventricular tachycardia could be converted to a sinus (n = 5) or normofrequent atrioventricular rhythm (n = 1). The mean postoperative defibrillation threshold was 2.7 +/- 2.1 J, with a mean shock impedance of 50.2 +/- 6.8 omega. CONCLUSIONS: The temporary atrial patch electrode allows low-energy defibrillation of episodes of atrial fibrillation. It may serve as an alternative therapeutic option for the treatment of supraventricular tachycardia. Szabó G, Bahrle S, Bátkai S, Stumpf N, Dengler TJ, Zimmermann R, Vahl CF, Hagl S (1998): L-arginine: effect on reperfusion injury after heart transplantation World J Surg. 1998 Aug; 22(8): 791-7; discussion 797-8 Abstract:Global myocardial ischemia and reperfusion injury play a major role in early postoperative myocardial graft dysfunction. The aim of the present study was to investigate the effects of the nitric oxide (NO) precursor L-arginine on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After 1 hour ischemic preservation, reperfusion was started after application of placebo (control, n = 12) or L-arginine (L-Arg 40 mg/kg, n = 12), a substrate of NO synthesis. Myocardial blood flow (MBF) was assessed by the hydrogen clearance method. An implanted balloon was used to obtain pressure-volume relations of the transplanted heart. Left ventricular developed pressure (LVDP), rate of pressure development (dP/dt), end-diastolic pressure (LVEDP), isovolumic relaxation constant (TE), and MBF were measured after 60 minutes and 24 hours of reperfusion. endothelium-dependent vasodilatation in response to acetylcholine (ACh) and endothelium-independent vasodilatation in response to sodium nitroprusside (SNP) were also determined. After 1 hour the MBF was significantly higher in the L-Arg group (3.6 +/- 0.6 vs. 1.9 +/- 0.2 ml/min/g, p < 0.05). The L-Arg group showed better recovery of systolic function and myocardial relaxation (LVDP 106 +/- 6 VS. 70 +/- 7 mmHg, p < 0.05; maximal dP/dt 5145 +/- 498 vs. 3410 +/- 257 mmHg/s, P < 0.05; TE 12.1 +/- 0.9 vs. 16.1 +/- 1.5 ms, p < 0.05, at an intraventricular volume of 80 microliters). LVEDP was similar in the two groups. After 24 hours no difference was found between the groups for basal MBF, LVP dP/dt, TE, LVEDP, or the response of MBF to SNP. However, ACh led to a significantly higher increase in MBF in the L-Arg group (52 +/- 8% vs. 29 +/- 7%, p < 0.05). These results indicate that (1) NO donation improves myocardial and endothelial functional recovery during early reperfusion after heart transplantation; and (2) initial treatment with L-Arg has a persisting beneficial effect against reperfusion-induced graft coronary endothelial dysfunction during late reperfusion. Szabó G, Bátkai S, Bahrle S, Dengler TJ, Vahl CF, Zimmermann R, Hagl S (1998): Effects of nitric oxide synthesis on reperfusion injury and catecholamine responsiveness in a heterotopic rat heart-transplantation model J Cardiovasc Pharmacol. 1998 Feb; 31(2): 221-30 Abstract:Global myocardial ischemia and reperfusion injury play a major role in early postoperative graft dysfunction. In this study, the influence of nitric oxide (NO) on reperfusion injury and catecholamine sensitivity after ischemia was investigated in a heterotopic rat heart-transplantation model. After a 1-h ischemic preservation, reperfusion was started either after application of saline vehicle (control, n = 8) or nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, n = 8) for inhibition of NO synthesis or NO-precursor L-arginine (L-Arg; 40 mg/kg, n = 8), or L-NAME plus L-Arg (n = 8), respectively. After 60 min of reperfusion, continuous dobutamine infusion (5 microg/kg/min) was started. Myocardial blood flow was assessed by the hydrogen-clearance method. An intraventricular balloon was used to measure pressure-volume relations: peak left ventricular pressure, the rate of pressure development (dP/dt), end-diastolic pressure, and isovolumic relaxation constant. Myocardial blood flow was significantly reduced after L-NAME and increased after L-Arg in comparison with control (p < 0.05). The L-NAME group showed decreased systolic and diastolic functional recovery in comparison with control. Simultaneous infusion of L-Arg and L-NAME reversed these effects. L-Arg alone led to a further improvement of cardiac functional recovery. Whereas myocardial blood flow remained unchanged in the L-NAME group with dobutamine infusion, it significantly increased in the control group (p < 0.05). L-Arg antagonized this effect of L-NAME. Dobutamine increased peak left ventricular pressure and dP/dt and shortened the isovolumic relaxation constant in all groups; however, the changes of systolic hemodynamic indices were significantly smaller in the L-NAME group (p < 0.05) and significantly higher in the L-Arg group (p < 0.05). These results indicate that (a) NO production within the graft during reperfusion has a significant beneficial effect on graft function, and (b) NO formation may play an important role in beta-adrenergic responses after heart transplantation. Szabó G, Sebening C, Hagl C, Tochtermann U, Vahl CF, Hagl S (1998): Right ventricular function after brain death: response to an increased afterload Eur J Cardiothorac Surg. 1998 Apr; 13(4): 449-58; discussion 458-9 Abstract: A major cause of early postoperative morbidity and mortality after cardiac transplantation is right ventricular (RV) failure which is attributed to the inability of the donor's RV to acutely compensate for the recipient's elevated pulmonary vascular resistance. This study was performed to determine: (1) the acute effects of brain death on the RV function; and (2) the adaptation potential of the RV to a progressive increase in RV afterload. METHODS: In 13 anesthetized, open-chest dogs (eight with brain death vs. five control with sham operation), brain death was induced by inflation of a subdural balloon catheter. Heart rate, RV systolic and end-diastolic pressure (RVSP, RVEDP), pulmonary arterial pressure (PAP), and cardiac output (CO), and pressure-length loops (sonomicrometry) were recorded. Afterload increase was induced 2 h after brain death induction by constriction of the pulmonary artery with an increase in RVP from 25 to 50 mmHg in 5 mmHg steps. RESULTS: Cushing phenomenon occurred within a few minutes after brain death induction, with a significant increase of HR (229 +/- 10 vs. 89 +/- 6 min(-1), P < 0.001), CO (3.2 +/- 0.2 vs. 1.7 +/- 0.1 l/min, P < 0.001), PAP (30.4 +/- 2.5 vs. 15.5 +/- 1.3 mmHg, P < 0.01) RVSP (55 +/- 5 vs. 23 +/- 2 mmHg, P < 0.001) and RVEDP (7.4 +/- 0.9 vs. 3.3 +/- 0.6 mmHg, P < 0.001). All these values were also significantly (P < 0.01) higher than the time corresponding values of the control group. The analysis of the pressure-length loops showed a hypercontractile state. Within 15-60 min, all parameters turned to baseline and remained stable for up to 2 h. When afterload was increased progressively, RVEDP increased markedly in the brain death and slightly in the control group (9.4 +/- 0.7 vs. 4.2 +/- 1.1 mmHg, P < 0.01, at RVSP = 50 mmHg). On the other hand, the increase of peak positive dP/dt was significantly higher in the control group (430 +/- 37 vs. 644 +/- 55 mmHg/s, P < 0.01, at RVP = 50 mmHg). However, global RV pump function characterized by CO and stroke work was similar in both groups. While regional RV contractility remained unchanged in the brain death group in terms of pressure-length relationships, RV contractility significantly increased in the control group. CONCLUSION: (1) Brain death per se does not result in an acute impairment of RV function. (2) While control animals adapt to an increased afterload by the homeometric, as well as the heterometric regulation, after brain death, an increase in RV preload follows elevations in RV afterload by the Frank-Starling mechanism subserving the increased stroke work required to ensure unchanged pump function. Vahl CF, Timek T, Bonz A, Fuchs H, Dillmann R, Hagl S (1998): Length dependence of calcium- and force-transients in normal and failing human myocardium J Mol Cell Cardiol. 1998 May; 30(5): 957-66 Abstract:Two questions were analysed: (1) Is the Frank-Starling mechanism operative in failing human myocardium? (2) Are length-dependent changes in force accompanied by length-dependent changes in intracellular calcium transients in human myocardium? METHODS: (I) in electrically stimulated left-ventricular trabeculae [normal donor heart (NDH), n = 8; end stage dilated cardiomyopathy (DCM), n = 11], isometric force development was analysed as a function of muscle length (37 degrees C, oxygenated Krebs-Henseleit solution, supramaximal electrical stimulation, frequency: 1 Hz). (II) Myocardium from the same patients were loaded with the fluorescent dye FURA-2/AM for simultaneous measurements of intracellular calcium transient (ICT) and force development at different muscle lengths. Muscle length, resting force, developed force and intracellular Calcium ("ratio method") were monitored continuously. RESULTS: (I) developed force increased up to an optimum as a function of muscle length in NDH- and DCM-myocardium. The slope of this increase was flatter in DCM-myocardium (P < 0.01). (II) In NDH- and DCM-myocardium, diastolic and systolic calcium increased significantly with muscle length. With decreasing muscle lengths the ICT became broader, the diastolic decay was retarded and the peak of the ICT was flatter. At Lmax the calcium amplitude was 23% smaller in DCM than in NDH (P < 0.04). CONCLUSION: there is a clear length dependence of active force in DCM-myocardium. The length dependence of force development is associated with length-dependent modulations of the ICT. The flatter slope of the length-force curve in DCM may be partly explained by altered intracellular calcium handling in failing myocardium. 1997: Bauernschmitt R, Lange R, De Simone R, Hagl S (1997): [Surgical treatment of acute endocarditis--which preoperative diagnosis does the surgeon need?] Langenbecks Arch Chir Suppl Kongressbd. 1997; 114: 1370-2 Abstract:In a group of 140 patients undergoing operation for acute infectious endocarditis in an 8 year period, the value of preoperative diagnostic procedures was analyzed in a retrospective study. Echocardiography was sufficient to establish the diagnosis in each case, angiography did not add any information about the endocarditis, but detected severe coronary heart disease in 19 patients. Abdominal sonography is mandatory to exclude intestinal foci, while CT scan of the brain only has to be performed in patients with neurologic deficits. Bonz A, Vahl CF, Hagl S (1997): Contractile behaviour and intracellular calcium during afterloaded contraction in mitral valve disease Thorac Cardiovasc Surg. 1997 Dec; 45(6): 280-6 Abstract:It was the aim of the present study to analyze left-ventricular contractile behaviour (force development, shortening) and intracellular calcium handling using afterloaded contractions of papillary muscle fibres from patients operated upon for mitral valve stenosis (MVS, n = 12) or mitral valve incompetence (MVI, n = 15). Isometric force development and passive resting tension at Lmax were similar in MVI and MVS (n.s.). Isotonic shortening amplitudes were reduced in MVI (p < 0.0001) compared to MVS. The peak intracellular calcium transient (ICT) preceeded the maximum force- and shortening amplitude in MVI and MVS. The amplitude of the ICT rose with decreasing afterload, became broader during shortening and presented a prolongation of the diastolic decay. Those differences were much more pronounced in MVI. The calcium-time integral (CTI) at minimal load (isotonic contraction) was 119 +/- 5% in MVS and 165 +/- 14% in MVI (p < 0.0001). The data reveal a severe diastolic calcium overload during shortening in left-ventricular MVI myocardium. An increased dissociation rate of calcium from the contractile proteins during shortening, a depressed calcium re-uptake into the sarcoplasmic reticulum during shortening, or altered mechanosensitive ion channels in MVI may be involved. Hagl C, Szabó G, Sebening C, Tochtermann U, Vahl CF, Sonnenberg K, Hagl S (1997): Is the brain death related endocrine dysfunction an indication for hormonal substitution therapy in the early period ? Eur J Med Res. 1997 Oct 30; 2(10): 437-40 Abstract:Experimental studies in animals have suggested that brain death (BD) -- related endocrinological dysregulations lead to a significant depression of cardiac pump and muscle function, however, the discussion about the relative extent of this influence remains controversal. The aim of the present study was to assess in an open chest animal model the short time course (5 hours) of hormonal (epinephrine, norepinephrine, T3, T4, ACTH, cortisol, insuline) and metabolic (glucose, lactate) changes in 10 brain dead dogs with special respect to the hemodynamic stability and myocardial pump function. After the onset of BD the concentrations of all hormonal parameters showed a significant decrease. Despite these changes, and in contrast to other studies, an adequate pump function (filling pressures, cardiac output) and muscle function (LVdp/dt) could be maintained by exclusive volume substitution without the use of hormonal or pressor agents. We conclude that in the present model a sufficient pump and muscle function can be maintained by adequate volume substitution, exclusively. The significant fall in adrenal and thyroid hormones had no direct effects on heart functional parameters in the first 5 hours after experimental BD induction. Hagl S, Jakob H, Sebening C, van Bodegom P, Schmidt K, Zilow E, Fleischer F, Ulmer H (1997): External stabilization of long-segment tracheobronchomalacia guided by intraoperative bronchoscopy Ann Thorac Surg. 1997 Nov; 64(5): 1412-20; discussion 1421 Abstract: Symptomatic obstruction of long segment tracheal or bronchial portions either related to congenital instability or secondary to vascular compression are rare malformations, which remain difficult to manage. A method of external tracheal or bronchial stabilization is described. METHODS: From July 1992 to April 1995, 7 children (age range, 4 months to 4 years; mean age, 19 months) and 1 adult (age, 46 years) were operated on for severe respiratory insufficiency. In 4 cases of congenital tracheal instability, 2 children had associated type IIIb esophageal atresia. Both children with esophageal atresia had previous operations (two and three times, respectively): 1 child had aortopexy and division of a patent ductus arteriosus and another child had distal tracheal resection elsewhere, both without relief of malacia. All children were intubated and ventilated since birth for 11 to 15 months. Secondary tracheobronchomalacia due to vascular compression was seen in 4 patients caused by double aortic arch (n = 2) and persisting ligamentum arteriosum after previous ligation of a patent ductus arteriosus (n = 2), with 1 child ventilated thereafter for 5 months. Operation was performed with the aid of extracorporeal circulation in all patients but 1, and consisted of transection of vascular rings and persistent ligamentum Botalli (n = 5), closure of multiple ventricular septal defects (n = 1) and extensive mobilization of the tracheobronchial tree as well as the great arteries. External stabilization of the severely dysplastic distal trachea (n = 6) or left main bronchus (n = 2) was achieved by suspending the malacic segment within an oversized and longitudinally opened ring-reinforced polytetrafluoroethylene prosthesis. Multiple plegeted sutures were placed extramucosally to the dysplastic tracheal wall and the dyskinetic pars membranacea, as well as to the polytetrafluoroethylene prosthesis in a radial orientation. Guided by simultaneous video-assisted bronchoscopy, reexpansion of the collapsed segments was achieved by gentle traction on the sutures while tying. RESULTS: Stenosis-free tracheobronchial reexpansion was achieved in all patients, as seen on repeated bronchoscopies during hospitalization and thereafter. All patients were extubated within 1 to 12 days after the operation. There was one late death, unrelated to the procedure, in a 31-month-old child 20 months after the operation. All other patients are free of stridor and in excellent clinical condition 21 to 54 months (mean, 38 months) thereafter. CONCLUSIONS: The presented method of bronchoscopically guided external tracheobronchial suspension within a ring-reinforced polytetrafluoroethylene prosthesis immediately relieves severe malacia of the trachea or main bronchi in infants as well as adults without necessitating resection. Midterm preliminary data suggest that growth potential of the affected segment exists within the oversized polytetrafluoroethylene prosthesis. Haass M, Serf C, Gerber SH, Kruger C, Haunstetter A, Vahl CF, Nobiling R, Kubler W (1997): Dual effect of digitalis glycosides on norepinephrine release from human atrial tissue and bovine adrenal chromaffin cells: differential dependence on [Na+]i and [Ca2+]i J Mol Cell Cardiol. 1997 Jun; 29(6): 1615-27 Abstract:It was the aim of the present study (1) to characterize the influence of Na+/K(+)-ATPase inhibition by the digitalis glycoside ouabain on both spontaneous and nicotine-evoked norepinephrine release from the human heart; and (2) to further investigate the role of glycoside induced changes in [Na+]i and [Ca2+]i (determined by microfluorimetry) for catecholamine release. The latter experiments were performed in bovine adrenal medullary chromaffin cells (BCC), an established cell culture model for sympathetic nerves. Ouabain (1-1000 mumol/l) exerted a dual effect on norepinephrine release (determined by HPLC) from incubated human atrial tissue: (I) Ouabain induced a concentration-dependent increase in norepinephrine release, that was calcium-independent and almost completely prevented by blockade of the uptake1-carrier by desipramine (1 mumol/l). The characteristics of this release process are consistent with a non-exocytotic mechanism. (II) In addition, ouabain augmented the nicotine-evoked (1-100 mumol/l) calcium-dependent norepinephrine release, which can be considered to be exocytotic. Na+/K(+)-ATPase inhibition also reduced the threshold concentration of nicotine from 10 to 1 mumol/l and it delayed the rapid tachyphylaxis of its norepinephrine releasing effect in human atrial tissue. In BCC, ouabain increased [Na+]i, [Ca2+]i and [3H]-norepinephrine release in parallel. Under calcium-free conditions, not only the ouabain-induced increase in [Na+]i, but also [3H]-norepinephrine release were enhanced. The ouabain-induced [3H]-norepinephrine release was always closely related to changes in [Na+]i, indicating a key role of [Na+]i for this calcium-independent non-exocytotic norepinephrine release. In addition, pretreatment with ouabain (1 mmol/l) augmented the nicotine-evoked (0.1-10 mumol/l) increments in [Na+]i, [Ca2+]i and [3H]-norepinephrine release. As nicotine-induced norepinephrine release depends on an increase in both [Na+]i and [Ca2+]i, these findings are indicative of an ouabain-mediated facilitation of exocytosis. In conclusion, increasing [Na+]i and [Ca2+]i inhibition of Na+/K(+)-ATPase by ouabain triggers non-exocytotic norepinephrine release, and facilitates nicotine-evoked exocytotic norepinephrine release. Jakob H, Kamler M, Hagl S (1997): Doubly angled pleural drain circumventing the transcostal route relieves pain after cardiac surgery Thorac Cardiovasc Surg. 1997 Oct; 45(5): 263-4 Abstract:Standard pleural drainage after cardiac surgery is accomplished through the intercostal space and the divided parietal pleural, often causing severe additional chest pain. To circumvent this route of insertion a doubly angled polyvinyl chloride drain was developed which can be placed via the median approach through the rectus abdominis muscle just beside the anterior mediastinal drains without irritation of the heart and parietal pleura into the phrenico-costal sinus. Kamler M, Jakob H, Lehr HA, Gebhard MM, Hagl S (1997): Direct visualization of leukocyte/endothelial cell interaction during extracorporeal circulation (ECC) in a new animal model Eur J Cardiothorac Surg. 1997 May; 11(5): 973-80 Abstract: The clinical complications of extracorporeal circulation (ECC) have been linked to a systemic activation of cellular and humoral components and to a dysregulation of the microcirculatory compartment. Since to date only in vitro methods exist for evaluation, we developed an animal model to study the effects of ECC on the microcirculation. To establish the model, we assessed whether these effects are dependent on the duration of ECC. METHODS: Intravital fluorescence microscopy was used on the dorsal skinfold chamber preparation in chronically instrumented, awake Syrian golden hamsters. ECC was realized using a micro rollerpump and a silicon tube shunting blood between the carotid artery and the jugular vein. ECC was performed in three groups for various times (2, 10 and 20 min) after application of heparin at 300 IU/kg body wt. In hamsters, the application of high dose heparin releases endothelial bound superoxide dismutase (SOD), a natural scavenger of oxygen derived free radicals. Protocol II assigned two groups receiving heparin at different doses of 50 and 2000 IU/kg body wt. RESULTS: ECC for 2 min served as control to exclude effects from hemodilution and resulted in a minimal induction of leukocyte/endothelial cell interaction. Isovolemic ECC for 20 min resulted in an increase in rolling (from 11 +/ 3 to 38 +/ 20%, mean +/- S.D., P < 0.05) and adherent leukocytes (from 19 +/- 16 to 215 +/- 145 cells/mm2, mean +/- S.D., P < 0.05) in postcapillary venules. Microhemodynamic parameters and functional capillary density were not significantly affected. Arterial blood pressure and heart rate were stable. Heparin at 2000 IU/kg inhibited post-ECC leukocyte adhesion following ECC, whereas 50 IU/kg showed no protective effects. CONCLUSIONS: Leukocyte/endothelial cell interaction, induced by blood contact with synthetic surfaces, was directly visualized in vivo. The number of adherent leukocytes was dependent on the duration of ECC. The application of high-dose heparin followed by release of SOD almost prevented leukocyte activation, suggesting a formation of oxygen free radicals during ECC. The new application of the hamster model may allow to study the underlying pathomechanisms and to develop therapeutic/prophylactic strategies to avert problems associated with ECC. Lange R, Thielmann M, Hagl S (1997): [Dynamic cardiomyoplasty] Herz. 1997 Oct; 22(5): 253-61 Abstract:Between 1965 and 1995 the incidence of heart failure has been constantly rising and the mortality from this disease has increased fivefold. The introduction of ACE inhibitors and of adrenergic beta blockers have resulted in major symptomatic improvements in patients with mild to moderate heart failure. For end stage disease, heart transplantation offers by now the only therapeutic option and yields excellent results. The permanent implantation of left heart assist devices is just gaining increasing importance. Yet, both methods also have inherent drawbacks and may not be available to all patients, so that new methods are constantly evaluated. Cardiomyoplasty was introduced into clinical practice in 1985 by Alain Carpentier and since then more than 700 patients have been operated worldwide. After dissection of the latissimus dorsi muscle it is wrapped around the heart in a clockwise fashion (Figure 1). Two sensing electrodes are placed on the anterior aspect of the right ventricle and two stimulation electrodes between the proximal branches of the thoracodorsal nerve (Medtronic SP 5548). The electrodes are then connected with a burststimulator (Cardiomyostimulator, Medtronic 4710) (Figure 2). During the first 2 weeks following the operation the muscle is not stimulated in order to allow for the healing process. Thereafter, a stimulation protocol with a programmed, staged increase of the stimulation frequency is started, to induce transformation of the skeletal muscle into a "fatigue resistant" tissue. After 3 months the muscle is stimulated with every second heart beat (2:1 mode) with full burstimpulses containing 6 single impulses per burst for a duration of 185 ms (Figure 3). Cardiomyoplasty was conceived for patients in NYHA III and severely impaired myocardial function, in whom drug treatment does not produce the expected benefits. The criteria for patient selection are strictly followed, since it has been shown in the past, that the preoperative condition of the patient is of specific importance for the postoperative outcome. Contraindications are NYHA IV, advanced right ventricular dysfunction, secondary pulmonary hypertension (> 600 dyn x s x cm 5), LV end-diastolic diameter > 70 mm und AV-valve incompetence > Grad II. Between July 1985 und October 1996 647 patients received a cardiomyoplasty with the Medtronic Cardiomyoplasty System and the results from 438 patients were analyzed from the "Worldwide Cardiomyoplasty Study Group". One and 2 years following the operation NYHA-class had improved by one class in 41.9% and 53.3%, respectively, and by 2 classes in 38.1% and 30.5%, respectively. In 16% and 15% no improvement was found (Figure 4). Prospective investigation of the quality of life by a score revealed a considerable improvement in the level of daily activities and social interaction. In contrast, two years after the operation, only a small, but significant increase in LV-EF from 22.9 +/- 8.1% to 25.8 +/- 9.7% (p < 0.05) was shown. Heart rate, maximal O2-consumption, total exercise time, cardiac index, stroke volume and stroke work index did not change. According to the results of a recent FDA-study, in-hospital mortality was 12% between 1991 and 1993, and was reduced during a second phase starting 1994 to < 3%. One, 2 and 3-year survival of 349 patients who were in NYHA-III prior to the operation was 69%, 56% und 47%, respectively. 43 patients who were operated in NYHA IV exhibited considerably worse survival with only 48% after 1 year and 30% after 2 years, respectively. In a subgroup of 103 patients with a statistically low operative risk, 1, 2 and 3-year survival was 77%, 71% und 61%, respectively (Figure 5). As a mechanism of action the skeletal muscle wrap exerts some active improvement of systolic wall motion of the heart/skeletal muscle complex. However, probably more important is an acute and chronically persisting shift of the pressure-volume relation to the left. This process results in a "reverse remodel Lange R, Thielmann M, Schmidt KG, Bauernschmitt R, Jakob H, Hasper B, Ulmer H, Hagl S (1997): Spinal cord protection using hypothermic cardiocirculatory arrest in extended repair of recoarctation and persistent hypoplastic aortic arch Eur J Cardiothorac Surg. 1997 Apr; 11(4): 697-702 Abstract: In recurrent coarctation collateral circulation may not be sufficient to maintain adequate perfusion of the lower body during the period of surgical repair. Different techniques such as interposition of a Gott-shunt, use of left heart bypass or hypothermic cardiocirculatory arrest are used to prevent spinal cord injury. METHODS: Twenty-eight operations for recurrent coarctation were performed in 26 patients following end-to-end anastomosis (58%), patch plasty (21%), subclavian flap aortoplasty (14%) and graft interposition (7%). Associated cardiac defects were present in 77% of the patients. Eleven patients who had adequate (> 50 mmHg) distal perfusion pressure during a test occlusion were operated on using simple cross-clamping (group I, mean age 8.5 +/- 3.8 years). In group I, end-to-end anastomosis was performed in nine patients and graft interposition in two patients. In 17 cases (including two patients from group I) with insufficient collateral circulation and with persistent hypoplasia of the arch, hypothermic cardiocirculatory arrest was used (group II, mean age 12.8 +/- 9.6 years). In group II end-to-end anastomosis was performed in three patients and graft interposition in 14 patients. Mean bypass-time was 116 +/- 36 min and arrest-time 33 +/- 16 min. Hypothermic cardiocirculatory arrest was begun when nasopharyngeal temperature was below 20 degrees C, corresponding to a rectal temperature of 24 +/- 3 degrees C. RESULTS: Hypothermic cardiocirculatory arrest allowed open reconstruction of the arch and/or complete or partial replacement of the arch and the coarctation segment. In-hospital mortality was 0 and 5.9% in group I and II, respectively. The one patient who died in group II had simultaneous correction of an anomalous pulmonary venous connection and death was unrelated to the method of coarctation repair. Reversible laryngeal nerve paresis was observed in two patients in group II, no other neurologic complications were observed in either group. Postoperative gradients over the repair site were less than 20 mmHg by Doppler-echocardiography. Two patients of group I had to have a second, early reoperation because of stenosis at the anastomotic site. Reconstruction of the distal aortic arch was then performed during hypothermic cardiocirculatory arrest. CONCLUSIONS: The use of hypothermic cardiocirculatory arrest in this special indication is a safe method which allows open reconstruction of the coarctation site and the aortic arch and protection of the spinal cord. The need for early reoperation because of inadequate repair may be reduced. Osswald BR, Vahl CF, Fleischer F, Hagl S (1997): Successful revascularisation for unstable angina of a patient with asymptomatic bilateral internal carotid occlusion, 70% stenoses of the external carotid arteries, and other circulation disturbances Thorac Cardiovasc Surg. 1997 Aug; 45(4): 200-3 Abstract:Nowadays, advanced surgical and anaesthesiological techniques of coronary artery bypass grafting minimize the risk of severe complications in patients with advanced arteriosclerotic cerebrovascular disease. Nevertheless, in case of highly compromised cerebrovascular status, the decision whether to undertake coronary artery bypass grafting or not requires special patient-related consideration. A severe, unstable angina made it necessary to perform coronary bypass grafting in a patient with bilateral internal carotid occlusion, a bilateral mid-stage stenosis of both external carotid arteries, a diminished flow within the right vertebral artery, and a subsequently impaired intracranial blood flow. Intraoperatively, besides the usual hemodynamic measurements, laser-Doppler flow probes were placed on the left and right upper temple to monitor relative changes of the cerebral blood supply. Using an individual perioperative management, the patient experienced a normal postoperative course and was discharged in good condition. Sack FU, Lange R, Mehmanesh H, Amman K, Schnabel P, Zimmermann R, Dengler T, Otto HF, Hagl S (1997): Transferral of extrathoracic donor neoplasm by the cardiac allograft J Heart Lung Transplant. 1997 Mar; 16(3): 298-301 Abstract:The transference of neoplasm from the donor to the recipient is a rare but recognized complication of organ transplantation. It has been reported after kidney transplantation from cadaver donors. We report a case in which an extrathoracic tumor was transmitted by the donor heart. The donor heart was harvested from a 46-year-old local donor and immediately transplanted to a 62-year-old female recipient. While implantation was performed, a hypernephroma was detected in the multiorgan donor. The ongoing heart transplantation could not be stopped. Four weeks after operation, the patient was discharged from the hospital. During the first year after transplantation, the clinical course was uneventful. One year after operation, the patient was admitted to the hospital with symptoms of weakness and fever. A right facial hemiparesis occurred, and a soft tumor was palpable subcutaneously in the right supraorbital region. Histologic examination revealed a malignant tumor with characteristics identical to the donor hypernephroma. In spite of chemotherapy and radiation therapy, dramatic tumor progression occurred with multiorgan metastases, which led to the death of the patient 2 months after admission. Schulz S, Bauernschmitt R, Albers J, Riesenberg A, Schwarzhaupt A, Vahl CF, Kiencke U (1997): A mathematical high time resolution model of the arterial system under extracorporeal circulation Biomed Sci Instrum. 1997; 33: 406-11 Abstract: The purpose of the following study was to establish a computer-generated model of the hemodynamic effects of pulsatile extracorporal perfusion describing flow and pressure parameters in the body for any given input flow patterns. METHODS: The human arterial tree was delineated according to a 128-branch model encompassing bifurcations and linear physical properties of the arterial walls. The distribution of flow and pressure waves was calculated based on a refined 3-element windkessel model. Autoregulatory mechanisms of brain and kidneys were implemented. RESULTS: By providing a simulated, "pump-generated" flow curve as the input signal to the system, the model was able to create and display flow and pressure curves at a high time resolution in each part of the systemic circulation including reflection phenomena throughout any observation period chosen. The hemodynamic effects of different pump-flow patterns, age, variations in hematocrit, hypothermia and occlusion of arterial branches, like the renal artery, could be simulated. CONCLUSION: In an attempt to get closer to a mathematically based regulation of heart-lung machines, this model of computer generated extracorporeal circulation provides an initial step. Ongoing research is required for implementation of metabolic conditions and continuous approximation of the model of the real physiologic or pathologic situation. Schulz S, Bauernschmitt R, Schwarzhaupt A, Vahl CF, Kiencke U (1997): Description of the ventriculoarterial interaction dynamics using recurrence plot strategies Biomed Sci Instrum. 1997; 34: 269-74 Abstract: The classical description of ventriculoarterial coupling by calculating the ratio between the effective arterial elastance Ea to the end-systolic elastance Ees does not give insight into the underlying dynamics of the interaction between left-ventricular pressure (LVP) and aortic pressure (AOP) and flow (AOF). The aim of this study was to introduce a state space representation for the ventriculoarterial coupling and to quantify changes of the coupling state. METHODS: A ventriculoarterial state space orbit VAO was defined to be dependent on three variables: VAO = [LVP(t), AOP(t + delta t), AOF(t + delta t)]. Changes in the coupling effect directly or indirectly on the time series of these parameters. They reflect the actual state of the cardiovascular system. The time delay delta t between the LVP and the aortic signals takes respect to the short delay between the heart action and the resulting waves in the arterial tree. The recurrence map of the VAO(i) (i = 1 .. N, N = number of points) is constructed by plotting the index i of every single point on the orbit (x-axis) against the indices of his 10 nearest neighbors (y-axis) in distance. The data were recorded in 9 anaesthetized pigs with a sample frequency of 512 Hz over a period of 6 seconds using piezoelectric pressure sensors and a Doppler flowmeter. A control condition was compared to a total occlusion of the descending aorta as a strong artificial disturbance of ventriculoarterial interaction. The nonlinear parameters percent recurrence, percent determinism and the entropy were calculated from the plot. RESULTS: Periodic crossing points and forbidden zones in all plots identify the nonlinear character of the chosen variables. The recurrent patterns are less rigid for control conditions than for total occlusion. Entropy (2.3% rise) and determinism (24% rise) are significantly (p < 0.003) increased. Total aortic occlusion leads to more complex time correlation patterns. CONCLUSIONS: These results may reflect the loss of an ideal coupling state leading to a more complex deterministic behavior of the overall regulatory system. Because recurrence plots do not impose rigid constraints on data set size, stationarity, or statistical distribution, we hypothesize that this technique might be useful to describe the nonlinear dynamics between left ventricle and arterial system. Schulz S, Bauernschmitt R, Schwarzhaupt A, Vahl CF, Kiencke U (1997): Hemodynamic consequences of replacing the aorta by vascular grafts simulated in a mathematical model Biomed Sci Instrum. 1997; 34: 263-8 Abstract: Replacing parts of the aorta by a noncompliant vascular prosthesis results in marked alterations of the aortic input impedance and influences arterial hemodynamics. We propose a mathematical model of circulation able to predict hemodynamic changes after simulation of vascular grafting. METHODS: Using a mathematical 128-branch model of the human arterial system a digitized aortic flow wave was chosen as the input signal to this system. After determination of the modules of elasticity of native vascular tissue and customary prostheses in technical experiments, replacement of any part of the aorta with a prosthesis was simulated by increasing the elasticity in the parts desired. RESULTS: During control conditions, the model displayed a physiologic distribution of flow and pressure waves throughout the arterial system. Simulated replacement of the aorta resulted in an increase of pressure amplitude and a partial loss of the aortic "Windkessel" function. Calculation of the aortic input impedance showed an increase of the characteristic impedance, while the peripheral resistance remained unaltered. CONCLUSION: This mathematical model of the arterial circulation proves to be useful to simulate hemodynamic changes after implantation of vascular grafts. The results of the model analysis are consistent with previous work done in experimental setups. Szabó G, Bahrle S, Dengler TJ, Bátkai S, Vahl CF, Hagl S (1997): [Reducing perfusion damage after heart transplantation with the nitric oxide donor L-arginine] Langenbecks Arch Chir Suppl Kongressbd. 1997; 114: 7-10 Abstract:Global myocardial ischemia and reperfusion injury are important factors of early graft failure after heart transplantation. In the present study, a reduction of reperfusion injury by the NO donor L-Arginine was shown after isogenic intraabdominal heterotopic heart transplantation in Lewis rats. L-Arginine improves the recovery of systolic and diastolic function during early reperfusion, which may be attributed to the increased postischemic myocardial blood flow. In late reperfusion, L-Arginine has a persisting protective effect on the endothelial function of the graft with significantly improved endothelium-dependent vasodilatation. Thiele RI, Jakob H, Hund E, Genzwuerker H, Herold U, Schweiger P, Hagl S (1997): Critical illness polyneuropathy: a new iatrogenically induced syndrome after cardiac surgery? Eur J Cardiothorac Surg. 1997 Dec; 12(6): 826-35 Abstract: Critical illness polyneuropathy (CIP) is a newly described severe complication after open heart surgery leading to tetraplegia for weeks to months. The purpose of the study was to gather further information on critical illness polyneuropathy developing in patients after cardiac surgery and to evaluate the hypothetical risk factors possibly related to the onset of this neurological disorder. METHODS: From July 1994 to October 1995, 7 out of 1511 patients undergoing open heart surgery developed critical illness polyneuropathy, which was diagnosed on the basis of electromyographic and nerve conduction features. The only common clinical finding was an intensive care unit (ICU) stay beyond seven days, therefore a similar group of 37 patients staying longer than seven days in the intensive care unit during the same period of time was evaluated and retrospectively compared to the 7 patients developing critical illness polyneuropathy. Univariate analysis of several traits was performed to evaluate possible risk factors. RESULTS: 4 Out of 7 patients in the CIP group died, all due to multiple organ failure, in contrast to 3/37 patients in the control group, again due to multiple organ failure. Patients developing CIP were staying significantly longer in the ICU (62+/-3 versus 14+/-8 days, P < 0.01) and had a significantly longer time on ventilator support (50+/-28 versus 7+/-13 days, P < 0.01) The incidence of sepsis was significantly higher in the CIP group than in the control group (85.7 versus 10.8%, P < 0.01). Compared to the control group the proportion of patients receiving corticosteroids (100 versus 10.8%, P < 0.01) and increased dosages of epinephrine and norepinephrine was higher in the CIP group (85.7 versus 35.1%, P < 0.05). Furthermore, the proportion of patients requiring chronic venovenous hemodiafiltration was significantly elevated in the CIP group (85.7 versus 5.4%, P < 0.01). CONCLUSIONS: CIP, despite it's benign nature due to it's spontaneous remission in patients who survive, is a disturbing complication following cardiac surgery which is associated with high mortality, a prolonged stay in the ICU, as well as an extended time on ventilator support. Interventions like chronic hemodiafiltration, the application of corticosteroids and the administration of high doses of catecholamines are more frequent in patients with CIP. Whether this indicates a causal relationship remains to be elucidated. Vahl CF, Carl I, De Simone R, Meinzer HP, Thomas G, Hagl S (1997): [Calibration of clinical databanks with "virtual patients"] Z Kardiol. 1997 Jan; 86(1): 35-41 Abstract:The scientific value of multicenter studies is still questionable, as there are no methods available that allow to determine whether in fact identical items are recorded in the same way in different centers. Subjective classifications (for example according to the New York Heart Association (NYHA)), definitions of items, documentation habits and procedures may not be comparable in different hospitals. For that reason the concept of a "virtual patient" for calibration of database systems was developed as a new methodological approach. The "virtual patients" describes a computer program that includes and uses multimedia-tools to represent an exactly defined patient. A sound card enables a patient to talk and to represent intracardial and intrapulmonary sounds. Additional information including echocardiographic sequences, perioperative video sequences, x-ray analysis, angiograms, etc. is represented in the program. Thus during the perioperative course of a patient the complete relevant pre-, intra- and postoperative information regarding the patient is provided. Any physician participating in a multicenter study is asked to record the data of this virtual patient and to store it in a database system using the sheets applied in a multicenter study. As the patient is exactly defined (virtual patient) incorrect classifications and incomplete recordings, etc. can easily be detected and discussed. The virtual patient is a tool that allows calibration of database systems by direct comparison of the documentation technique between different physicians and different hospitals participating in multicenter studies. It is thus a multimedia-instrument to support standardization and quality assurance of database systems. Vahl CF, Osswald BR, Meinzer HP, De Simone R, Thomas G, Hagl S (1997): [Internal quality assurance or Hawthorne effect?] Langenbecks Arch Chir Suppl Kongressbd. 1997; 114: 260-6 Abstract:The tendency of study participation per se to affect outcome is described by the term Hawthorne effect. This process defines the first step for internal quality assurance. However, whenever an attempt is made to describe the effects of quality assurance in more detail specific mathematical tools are required, including a database system that allows the calculation of clinical profiles, problem profiles, time-related variance of variables, univariate and multivariate statistics, calculation of scores and application of the hazard function. However, it has to be considered that any mathematical model is a way to present a hypothesis and not a proof. Whenever a proof is required, one should not ask for internal quality assurance, but design a randomized study. Vahl CF, Timek T, Bonz A, Kochsiek N, Fuchs H, Schäffer L, Rosenberg M, Dillmann R, Hagl S (1997): Myocardial length-force relationship in end stage dilated cardiomyopathy and normal human myocardium: analysis of intact and skinned left ventricular trabeculae obtained during 11 heart transplantations Basic Res Cardiol. 1997 Aug; 92(4): 261-70 Abstract:The Frank-Starling-mechanism (FSM) was analyzed in isolated intact and skinned human left ventricular myocardium obtained from 11 heart transplantations (normal donor hearts (NDH), n = 8; dilated cardiomyopathy (DCM), n = 11). The new technique to utilize muscle strips from normal donor hearts which were actually implanted is described in detail. METHODS: I) In electrically stimulated left ventricular trabeculae (37 degrees C, oxygenated Krebs-Henseleit solution, supramaximal electrical stimulation, frequency 1 Hz) force development was analyzed as a function of muscle length (NDH = 8; DCM = 11). II) In an additional series left ventricular myocardium was demembranized ("skinned") by Triton-X-100. At different sarcomere lengths and calcium concentrations corresponding to pCa values of 4.3, 5.5, and 8.0 force development was measured (DCM = 11; NDH = 9). RESULTS: I) Developed force increased up to an optimum as a function of muscle length in intact NDH- and DCM-myocardium. However, the relative increment of developed force after any length step was smaller in DCM than in NDH. Near "Lmax" (muscle length associated with maximum developed force) passive resting tension was considerably elevated in DCM, indicating significantly increased diastolic stiffness. II) In skinned left ventricular DCM- and NDH-myocardium developed force depended on sarcomere length with an optimum near 2.2 microns. However, a reduction of activator calcium concentration from pCa 4.3 to pCa 5.5 produces a smaller percent decline in force at short sarcomere lengths in DCM than it does in NDH. CONCLUSION: The present study shows that except for diastolic stiffness and a smaller relative force increment after any length step in DCM the Frank Starling mechanism is still present in isolated human left ventricular DCM- as in NDH-myocardium. The current study does not allow to decide whether in skinned myocardium the smaller percent decline in force after reduction of activator calcium concentrations in DCM is caused by an increased calcium sensitivity at short sarcomere lengths or decreased sensitivity at long sarcomere lengths.

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