ABSTRACT: In heart transplantation a well-preserved myocardial ultrastructure is an important precondition for functional regeneration. Aim of the study is to optimize the conditions in this new established model of extracorporeal cardiac perfusion.
(I) In six pigs, hearts were arrested with Bretschneider Histidine-Tryptophan-Ketoglutarate cardioplegia and cold ischemia, explanted and connected to a circulating constant pressure Langendorff system (80-90mmHg) and perfused with leukocyte depleted autologous blood. (II) Beating hearts of seven pigs were explanted and connected immediately to the Langendorff system (40-50mmHg). Myocardial biopsies (n=55) were taken in situ and during the following 12h of reperfusion, and were prepared for electron microscopy.
Cardioplegia and hypothermia (group I) induced mitochondrial edema and myofibrillar degeneration in cardiomyocytes and severe endothelial edema. During 4h of reperfusion, mitochondrial edema, myofibrillar, and sarcolemmal damages in cardiomyocytes increased. Moderate endothelial degeneration, interstitial edema, and bleedings appeared. In contrast, in group II after 6h of reperfusion endothelia showed only mild alterations. Cardiomyocytes showed myofibrillary but not mitochondrial degeneration. Interstitial edema and bleedings were mild.
Avoiding cardioplegia and hypothermia, and using lower perfusion pressure resulted in a better preservation of the ultrastructure in explanted hearts at the Langendorff system.
European Journal of Cardio-Thoracic Surgery 03/2007; 31(2):214-21. · 2.55 Impact Factor
ABSTRACT: Adverse clinical consequences associated with conventional coronary artery bypass surgery (CCAB) have largely been attributed to cardiopulmonary bypass circuit (CPB), hypothermic cardiac arrest, aortic cannulation, and cross-clamping. Consequently, there has been a growing interest in safer alternatives to CCAB including off-pump beating-heart bypass surgery (OPCAB). Initial concerns regarding completeness of revascularization at the lateral wall were addressed by using modern stabilizers and heart positioning devices. First studies tended to be nonrandomized clinical reports rather than controlled clinical trials with the potential risk of unbalanced baseline characteristics leading to biases in favor of OPCAB. Since these early reports, several randomized trials including mixed-risk patient populations have been completed. Most of them failed to reveal superiority of OPCAB concerning mortality and major perioperative morbidity due to statistically underpowered design to detect clinically important but infrequent adverse outcome events. Likewise, in most of the recently published meta-analyses of randomized trials no difference in early mortality, myocardial infarction or stroke rate was found, but OPCAB was superior regarding blood loss, transfusion requirement, rethoracotomy, ventilation time, ICU (intensive care unit) and hospital stay and resource utilization as illustrated in Table 1. Most of the large observational studies comparing OPCAB and CCAB strategies demonstrated a benefit of OPCAB concerning early mortality, myocardial infarction and stroke rate as summarized in Table 2. However, in few published follow-up studies no significant differences concerning recurrence of angina, reintervention rate und late mortality were found. The decision between OPCAB and CCAB has to weigh several factors, including the likely risks and benefits of the two approaches for the particular patient, the experience of the surgeon, the complexity of the coronary disease, and the required coronary revascularization.
Herz 09/2006; 31(5):384-95. · 0.92 Impact Factor
ABSTRACT: Aim of this study was to compare the outcome of beating heart versus conventional coronary artery bypass graft (CABG) strategies in acute coronary syndromes for emergency indications.
638 consecutive patients with acute coronary syndrome (ACS) receiving emergency CABG surgery via midline sternotomy from January 2000 to September 2005 were evaluated. Propensity score analysis was used to predict the probability of undergoing beating heart (BH) (n=240) versus cardioplegic cardiac arrest (CA) (n=398) strategies. Patients presented with stable hemodynamics (n=531) or in cardiogenic shock (CS) (n=107). Hospital and follow-up outcome was compared by propensity score adjusted multiregression analysis. BH included 116 on-pump and 124 off-pump (OPCAB) procedures. There was a propensity to operate CS patients on the beating heart (multivariate odds ratio [OR], 3.8; P=0.001). Under stable hemodynamics significant predictors for BH selection were logEuroSCORE >20% (OR, 2.05), creatinine >1.8 mg/dL (OR, 4.12), complicated percutaneous coronary intervention (OR, 1.88), ejection fraction <30% (OR, 2.64), whereas left main disease (OR, 0.68), circumflex artery (OR, 0.32), and 3-vessel disease (OR, 0.67) indicated preference for cardioplegic arrest. Time from skin incision to culprit lesion revascularization was significantly reduced in BH patients. BH surgery led to a significant benefit in terms of less drainage loss, less transfusion requirement, less inotropic support, shorter ventilation time, lower stroke rate, and shorter intensive care unit stay. In CS, BH was associated with lower incidence of stroke, inotropic support, acute renal failure, new atrial fibrillation and sternal wound healing complications. In CS patients, hospital mortality rate was reduced when using beating heart strategies (P=0.048). Overall survival, major adverse cerebral and cardiovascular event rate, and repeated revascularization was comparable during a 5-year follow-up.
Beating heart strategies are associated with an improved hospital outcome and comparable long-term results for high-risk patients presenting acute coronary syndrome with or without CS.
Circulation 08/2006; 114(1 Suppl):I477-85. · 14.74 Impact Factor
ABSTRACT: Seit Mitte der 90er Jahre werden koronare Bypassoperationen auch ohne Verwendung der extrakorporalen Zirkulation als „off-pump
coronary artery bypass“ - Prozeduren (OPCAB) vorgenommen, um die Morbidität der extrakorporalen Zirkulation, des kardio plegischen
Herzstillstands und der transversalen Aortenklemmung zu vermeiden. Erste monozentrische, nichtkontrollierte Vergleichsstudien
zwischen der konventionellen Bypasschirurgie und der OPCAB-Chirurgie zeigten dabei eine Überlegenheit der OPCAB-Verfahren,
wobei diese überwiegend an Niedrigrisikopatienten vorgenommen wurden und eine Verfälschung der Ergebnisse zugunsten der OPCAB-Chirurgie
durch unbalancierte Patientencharakteristika meist nicht ausgeschlossen werden konnte. Bis heute liegt nun eine Vielzahl prospektiv-randomisierter
Studien an unselektionierten Kollektiven vor, die aber aufgrund der jeweils niedrigen Patientenzahl und der geringen Inzidenz
schwerer perioperativer Komplikationen das Signifikanzniveau zugunsten des einen oder anderen Verfahrens in der Regel nicht
erreichten. Auch in wenigen kürzlich erschienenen Metaanalysen der randomisierten Studien fand sich meist kein signifikanter
Unterschied bezüglich der perioperativen Mortalität sowie der Myokardinfarkt- und Schlaganfallrate. Eine Überlegenheit der
OPCAB-Chirurgie war hier jedoch bezüglich des Auftretens von Rethorakotomien, des perioperativen Blutverlusts, der Beatmungszeit,
der Transfusionspflichtigkeit und folglich der Intensiv- und Krankenhausliegedauer sowie des Ressourcenverbrauchs erkennbar.
Bis dato vorliegende große multizentrische Beobachtungsstudien belegen meist einen Vorteil der OPCAB-Chirurgie bezüglich perioperativer
Mortalität, Myokardinfarkt- und Schlaganfallrate. Mittel- und langfristige Vergleichsuntersuchungen bezüglich Anginafreiheit,
Reinterventionsrate und Langzeitüberleben ergeben bislang keinen signifikanten Vorteil für das eine oder andere Verfahren.
Adverse clinical consequences associated with conventional coronary artery bypass surgery (CCAB) have largely been attributed
to cardiopulmonary bypass circuit (CPB), hypothermic cardiac arrest, aortic cannulation, and cross-clamping. Consequently,
there has been a growing interest in safer alternatives to CCAB including off-pump beating-heart bypass surgery (OPCAB, see
Figure 1). Initial concerns regarding completeness of revascularization at the lateral wall were addressed by using modern
stabilizers and heart positioning devices (Figure 2). First studies tended to be nonrandomized clinical reports rather than
controlled clinical trials with the potential risk of unba lanced baseline characteristics leading to biases in favor of OPCAB.
Since these early reports, several randomized trials including mixed-risk patient populations have been completed. Most of
them failed to reveal superiority of OPCAB concerning mortality and major perioperative morbidity due to statistically underpowered
design to detect clinically important but infrequent adverse outcome events. Likewise, in most of the recently published meta-ana
lyses of randomized trials no difference in early mortality, myocardial infarction or stroke rate was found, but OPCAB was
superior regarding blood loss, transfusion requirement, rethoracotomy, ventilation time, ICU (intensive care unit) and hospital
stay and resource utilization as illustrated in Table 1.
Most of the large observational studies comparing OPCAB and CCAB strategies demonstrated a benefit of OPCAB concerning early
mortality, myocardial infarction and stroke rate as summarized in Table 2. However, in few published follow-up studies no
significant differences concerning recurrence of angina, reintervention rate und late mortality were found.
The decision between OPCAB and CCAB has to weigh several factors, including the likely risks and benefits of the two approaches
for the particular patient, the experience of the surgeon, the complexity of the coronary disease, and the required coronary
Herz 07/2006; 31(5):384-395. · 0.92 Impact Factor
ABSTRACT: Intraoperative application of thermal coronary angiography based on dynamic infrared imaging leads to useful qualitative information concerning coronary artery bypass graft flow and anatomy. Additional quantitative flow estimation is desirable to detect graft failures. The aim of this study was to develop a heat-transfer model for quantitative flow estimation in an experimental setup. The first clinical results in coronary artery bypass grafting are reported.
Dynamic infrared imaging was applied in pig hearts to collect video data of the rewarming process of the left anterior descending artery supplied by antegrade perfusion. For mathematic description, we used the dynamic enthalpy balance for open systems, and a Laplace transformation was carried out. Therefore the time constant tau was calculated by performing a nonlinear fit procedure on the averaged dynamic temperature curves recorded over a left anterior descending artery segment. Subsequently, left internal thoracic artery-left anterior descending artery bypass graft flow was assessed intraoperatively. Effective left anterior descending artery flow was determined by using a transit-time flowmeter.
Tau is a system constant and changes depending on the flow and the system capacity. Assuming system capacity to be constant, tau only depends on the flow. It follows from the differential equation that there is a potential relation between tau and the flow. An excellent comparison (R2 = 0.968, P <.005) was demonstrated. By using the algorithms, quantitative flow estimation in pig hearts was possible. For clinical application, the formulas were applied to intraoperatively derived dynamic temperature curves with a good comparison to the actual left internal thoracic artery-left anterior descending artery flow.
The developed heat-transfer model allows for precise measurement of graft flow by using dynamic infrared imaging and can be applied for noninvasive graft flow estimation in beating-heart surgery.
The Journal of thoracic and cardiovascular surgery 06/2006; 131(6):1344-51. · 3.41 Impact Factor
ABSTRACT: We developed a novel whole blood assay to assess the effects of immunosuppressants on lymphocyte apoptosis.
Peripheral blood for six experiments for each drug was treated either with cyclosporin A (CsA), mycophenolate acid (MPA), tacrolimus (TRL) or rapamycin (RAPA). Whole blood was stimulated with different concentrations of staurosporine (0-5 microM) for 24 h. Using FACS, apoptosis were measured by Annexin V expression (%cells +/- SEM).
MPA, RAPA, TRL, but not CsA, increased (P < 0.05) apoptotic cells (MPA:20.9 +/- 3.7; RAPA:17.5 +/- 3.3; TRL:16.4 +/- 2.9 vs. control:15.2 +/- 2.8).
This new whole blood assay exhibited that MPA has a stronger effect on apoptosis than RAPA and TRL, whereas CsA had no effect.
Cytometry Part A 04/2006; 69(3):158-60. · 3.73 Impact Factor
ABSTRACT: Native coronary artery spasm is a very rare complication during off-pump coronary artery bypass grafting. We report the case of a 74-year-old man who experienced angiographically documentated right coronary artery spasm while undergoing off-pump coronary artery bypass grafting on the diseased left coronary system. Despite two episodes of ventricular fibrillation and persistent ST segment elevation of the posterior wall, the off-pump procedure was successfully completed by grafting the left internal thoracic artery to the left anterior descending artery and a saphenous vein graft to the Ramus intermedius. The immediate postoperatively performed coronary angiography demonstrated patent anastomoses and two areas of significant spasticity within the course of the right coronary artery. Intracoronary nitroglycerin infusion into the ostium of the right coronary artery resolved the spasms of this nondiseased vessel as well as the associated ST segment elevations.
Clinical Research in Cardiology 03/2006; 95(2):115-8. · 2.95 Impact Factor
ABSTRACT: We report the case of an 8-month-old male infant presenting with life-threatening ventricular tachycardia. Echocardiography revealed a left ventricular tumor. The tumor was resected through a left ventriculotomy, and the left ventricle was reconstructed after a partial ventriculectomy Histologic investigation showed a completely resected benign fibroma. The 30-year-old mother was known to have nevoid basal-cell carcinoma syndrome, which can be associated with cardiac fibromas. We believe that this is an interesting addition to the medical literature.
Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital 02/2006; 33(1):88-90. · 0.65 Impact Factor
ABSTRACT: Since only little is known on stem cell therapy in non-ischemic heart failure we wanted to know whether a long-term improvement of cardiac function in non-ischemic heart failure can be achieved by stem cell transplantation.
White male New Zealand rabbits were treated with doxorubicin (3 mg/kg/week; 6 weeks) to induce dilative non-ischemic cardiomyopathy. Thereafter, we obtained autologous bone marrow stem cells (BMSC) and injected 1.5-2.0 Mio cells in 1 ml medium by infiltrating the myocardium via a left anterolateral thoracotomy in comparison to sham-operated rabbits. 4 weeks later intracardiac contractility was determined in-vivo using a Millar catheter. Thereafter, the heart was excised and processed for radioligand binding assays to detect beta1- and beta2-adrenoceptor density. In addition, catecholamine plasma levels were determined via HPLC. In a subgroup we investigated cardiac electrophysiology by use of 256 channel mapping.
In doxorubicin-treated animals beta-adrenoceptor density was significantly down-regulated in left ventricle and septum, but not in right ventricle, thereby indicating a typical left ventricular heart failure. Sham-operated rabbits exhibited the same down-regulation. In contrast, BMSC transplantation led to significantly less beta-adrenoceptor down-regulation in septum and left ventricle. Cardiac contractility was significantly decreased in heart failure and sham-operated rabbits, but was significantly higher in BMSC-transplanted hearts. Norepinephrine and epinephrine plasma levels were enhanced in heart failure and sham-operated animals, while these were not different from normal in BMSC-transplanted animals. Electrophysiological mapping revealed unaltered electrophysiology and did not show signs of arrhythmogeneity.
BMSC transplantation improves sympathoadrenal dysregulation in non-ischemic heart failure.
Journal of Cardiothoracic Surgery 02/2006; 1:17. · 1.19 Impact Factor
ABSTRACT: Recent studies have demonstrated that transplanted bone marrow-derived stem cells (BMCs) possess a broad differentiation potential and are able to form new cardiomyocytes. However, the identity of BMCs as true cardiomyocytes is still ambiguous. Therefore, we investigated the fate of transplanted fluorescence labeled BMCs and cardiomyocytes in co-culture.
For cell tracking we used two different fluorescent probes, Vybrant/DiO and Vybrant/DiI. BMCs were taken from human sternal marrow, purified using a Ficoll-gradient-centrifugation, treated with 5-azacytidine and stained with Vybrant/DiO. Furthermore, isolated spontaneous beating cardiomyocytes of neonatal rats (CM) were labeled with Vybrant/DiI. Thereafter, the BMCs were transplanted into CM-cultures and investigated on day 1, 4, 7, 14 and 28 using two-color fluorescence phenotyping by laser-scanning-cytometry (LSC). Two-color positive cells were harvested by patch-clamp technique and beta-MHC mRNA expression was analyzed by single-cell PCR.
Two different morphological phenotypes were observed by LSC. First, isolated DiO labeled BMCs without contact or with direct cell contact to DiI labeled CMs. Second, some BMCs and CMs were double positive for DiO/DiI spontaneously forming hybrids. This population increased by 18% from day 1 to 4 and decreased only slightly until day 28. Additionally, few two-color positive cell formations expressed both human and rat specific beta-MHC mRNA as well as only human beta-MHC mRNA indicating that cell-fusion and transdifferentiation has occurred.
These observations provide in vitro evidence for spontaneous cell fusion and transdifferentiation of BMCs in co-culture, raising the possibility that the observed phenomenons may contribute to development or maintenance of these cell types.
European Journal of Cardio-Thoracic Surgery 12/2005; 28(5):685-91. · 2.55 Impact Factor
ABSTRACT: By maintaining native coronary blood flow in on-pump beating heart surgery (OnP-BH) and comparing with OPCAB strategy pump-related effects on myocardial injury and cardiac dysfunction could be specifically differentiated from ischemia/reperfusion-related consequences of surgical coronary revascularization.
In a randomized-prospective design, 40 elective patients with normal EF and three vessels coronary artery disease (left main disease excluded) were assigned to OPCAB or OnP-BH surgery. Before coronary occlusion and 1, 30, 60, and 90 min after reperfusion with the LIMA graft, coronary sinus (CS) blood was sampled to determine intraoperative myocardial ischemia (pH, lactate, pO2) and oxidative stress (malondialdehyde, MDA). Additionally to CS blood arterial blood was analyzed 4, 12, and 24 h postoperatively to determine myocardial necrosis (CK-MB, cardiac troponin I), myocardial dysfunction (NT-proBNP) and inflammation (C-reactive protein). Results: Groups were identical with regards to age and gender (OPCAB 63.0+/-6.0 versus OnP-BH 65.3+/-3.9 y, 20% female patients). Number of grafts were 3.0+/-0.5 in OPCAB versus 2.9+/-0.3 in OnP-BH (n.s.) with 44 versus 34% bilateral IMAs and 56 versus 50% complete arterial revascularization. Regarding ischemia, intraoperatively only lactate values increased significantly in the OnP-BH group. Significantly higher CK-MB and troponin I levels were found from LIMA-LAD flow release onwards to 4 h postoperatively in the OnP-BH group. NT-proBNP levels were significantly higher in the OnP-BH group during the entire study period. CRP levels were higher in the OnP-BH group 12 and 24 h postoperatively.
In this randomized study on routine coronary patients with normal ventricular function, OPCAB revealed less myocardial injury than OnP-BH. These findings implicate that CPB slightly affects the myocardium.
European Journal of Cardio-Thoracic Surgery 07/2005; 27(6):1057-64. · 2.55 Impact Factor
ABSTRACT: TIVES: We postulated a change of angiotensin II receptor subtype expression in patients with lone atrial fibrillation (AF) and AF with underlying mitral valve disease (MVD) both compared with sinus rhythm (SR).
Atrial fibrillation is a progressive disease associated with electrical and structural remodeling. Angiotensin II (ANGII) is involved in the process of myocardial remodeling. Actions of ANGII are mediated by ANGII receptor subtypes 1 and 2 (AT(1) and AT(2)).
Left atrial (LA) and right atrial (RA) tissue samples were obtained from patients with AF or SR with or without underlying MVD. The AT(1) and AT(2) protein levels were measured by quantitative Western blotting techniques.
The AT(1) protein level in the LA was significantly increased in patients with AF (all forms) compared with SR (p < 0.05), whereas AT(2) expression was not significantly altered. Comparison of the subgroups revealed a similar increase of AT(1) in both paroxysmal AF and chronic AF with or without MVD. Additionally, investigations of ANGII receptor subtypes in the RA did not exhibit any significant changes either in AT(1) or in AT(2) in patients with AF versus SR. Underlying MVD did not significantly affect AT(2) receptor subtype expression in LA.
Atrial fibrillation is associated with an up-regulation of AT(1) in LA, but not in RA, and did not appear to influence the AT(2) expression in the atrium. Because we found an enhanced expression of AT(1)in the LA, we conclude that AT(1) might be involved in the pathogenesis of AF in the LA.
Journal of the American College of Cardiology 12/2003; 42(10):1785-92. · 14.16 Impact Factor
European Journal of Cardio-Thoracic Surgery 11/2003; 24(4):641. · 2.55 Impact Factor