Thoracic Wall Reconstruction with Acellular Porcine Dermal Collagen Matrix.

BACKGROUND: Major thoracic wall resections require the implantation of foreign materials for reconstruction and stabilization. Recently, biological collagen matrixes have emerged as an alternative to the routinely used synthetic materials. MATERIALS AND METHODS: Retrospectively, we analyzed our initial experience of chest wall reconstruction on large defects using a cross-linked porcine dermal acellular collagen matrix mesh with a thickness of 1.5 mm. RESULTS: Six sarcoma patients with a mean age of 46 (22-66) years underwent chest wall resections. Complete thoracic wall defects (mean area 149 cm2) ranged from 8 × 10 to 15 × 20 cm in size. In the majority of cases, only mobilized subcutaneous tissue and skin were used for soft-tissue coverage of the implanted porcine collagen matrix patches. Implantation and postoperative courses were uneventful in all patients. No local infections or wound healing problems occurred. The collagen material resulted in durable and good to excellent chest wall stability in clinical follow-ups, and on computed tomography scans spanning over 3.5 years. Histological examination showed integration, neovascularization, and long-term persistence of the collagen matrix on late reoperation of one patient. CONCLUSION: Acellular porcine dermal collagen matrix is a feasible and reliable biological patch material for reconstruction of the thoracic wall. Excellent wound healing and long-term stability are achieved even in large defects or complete sternal replacements.

Local control in Ewing sarcoma of the chest wall: results of the EURO-EWING 99 trial.

BACKGROUND: Primary Ewing sarcoma (ES) can sometimes present as a chest-wall tumor. Multidisciplinary management, including chemotherapy and local treatment consisting of surgery, radiotherapy (RT), or both, has improved the survival of patients with localized ES; however, the best approach to achieving local control remains controversial. METHODS: We retrospectively analyzed data from 198 patients with non-metastatic ES of the chest wall, who were registered in the database of the German Society of Pediatric Hematology and Oncology between July 1998 and April 2009. The majority of patients (n = 130) presented with rib tumors; 7 patients received RT only, 85 patients underwent surgery alone, and 106 patients were treated with a combination of surgery and RT. RESULTS: Overall survival in all patients was 78 and 71 % at 3 and 5 years, respectively. Event-free survival at 5 years (5-year EFS) was 57 % in the RT group, 73 % in the surgery group and 63 % in the surgery + RT group. In patients with complete resections, 5-year EFS did not improve with the addition of RT compared with surgery alone. There was no difference in the 5-year EFS in patients with partial (63 %) or total (64 %) resection of the affected ribs, and median follow-up was 4.71 years (range 0.40-13.48). CONCLUSIONS: Complete tumor resection is the best way to achieve local control of ES of the chest wall; additional RT is only useful in patients with incomplete resection. The main limitation of this study was its retrospective nature, and the benefit of total resection of the affected ribs could not be proved.

Pectus excavatum and cardiac surgery: simultaneous correction advocated.

BACKGROUND: Severe pectus excavatum may be present in combination with cardiac conditions requiring open-heart surgery. The best strategy for this situation has been debated controversially. PATIENTS AND METHODS: In a retrospective study, we analyzed all our patients undergoing concurrent pectus excavatum correction and open-heart surgery. RESULTS: Ten patients aged 9 to 70 years underwent a simultaneous combined surgical procedure between 2001 and 2013. Indications for cardiac surgery were various forms of congenital and acquired heart disease including coronary artery disease with internal thoracic artery grafts and ascending aortic aneurysms. A modified Ravitch procedure was performed for pectus excavatum correction (mean Haller-Index 5.0). Mean operating time was 364 (210-495) minutes and mean duration of cardiopulmonary bypass was 125 (54-222) minutes. All procedures were completed successfully. Postoperatively minor complications were observed in three patients. In-hospital and 30-day mortalities were nil. Good cosmetic and functional results were achieved in all patients. CONCLUSIONS: Our data demonstrate that simultaneous pectus excavatum correction and cardiac surgery is effective and reliable. A combined approach is advocated if candidates for cardiac surgery present with significant pectus excavatum deformity.

Identification of HLA ligands and T-cell epitopes for immunotherapy of lung cancer.

INTRODUCTION: Lung cancer is the most common cancer worldwide. Every year, as many people die of lung cancer as of breast, colon and rectum cancers combined. Because most patients are being diagnosed in advanced, not resectable stages and therefore have a poor prognosis, there is an urgent need for alternative therapies. Since it has been demonstrated that a high number of tumor- and stromal-infiltrating cytotoxic T cells (CTLs) is associated with an increased disease-specific survival in lung cancer patients, it can be assumed that immunotherapy, e.g. peptide vaccines that are able to induce a CTL response against the tumor, might be a promising approach. METHODS: We analyzed surgically resected lung cancer tissues with respect to HLA class I- and II-presented peptides and gene expression profiles, aiming at the identification of (novel) tumor antigens. In addition, we tested the ability of HLA ligands derived from such antigens to generate a CTL response in healthy donors. RESULTS: Among 170 HLA ligands characterized, we were able to identify several potential targets for specific CTL recognition and to generate CD8+ T cells which were specific for peptides derived from cyclin D1 or protein-kinase, DNA-activated, catalytic polypeptide and lysed tumor cells loaded with peptide. CONCLUSIONS: This is the first molecular analysis of HLA class I and II ligands ex vivo from human lung cancer tissues which reveals known and novel tumor antigens able to elicit a CTL response.

Surgery on extracorporeal circulation in early and advanced non-small cell lung cancer.

BACKGROUND: Locally advanced (T4) non-small cell lung cancer (NSCLC) is principally amenable to surgery. For radical resection of cardiovascular structures, extracorporeal circulation (ECC) may be required. Tumor dissemination is a concern in this situation. In this study, we evaluate the long-term results of T4 NSCLC surgery with ECC and compare them with combined cardiopulmonary surgery for early-stage NSCLC and heart disease. METHODS: We retrospectively analyzed 16 patients undergoing surgery on ECC over a 13-year period. Eight patients suffered from T4 NSCLC (group A), and another eight patients suffered from coincidental T1-T2 NSCLC and heart disease (group B). RESULTS: In group A, five patients received neoadjuvant radiochemotherapy. Complete resection was achieved in all patients. Thirty-day mortality was one patient (12.5%) in each group. Six patients died from recurrent cancer with a median survival of 13.6 months in group A. Prognosis in patients with direct tumor invasion of the aortopulmonary window was a lot worse compared to those with atrial infiltration. One T4 patient who had only received surgery survived for 155 months without relapse. In group B, no NSCLC relapse occurred, and median survival was 21.6 months. All but one death in group B occurred due to cardiovascular incidents. CONCLUSIONS: Surgery on ECC for T4 NSCLC gives satisfactory results. The site of infiltration appears to be most important for local tumor relapse. Long-term survival is possible in some cases. Simultaneous cardiac and pulmonary surgery resulted in good early and midterm outcomes without surgery-induced tumor propagation.

Cerebral protection during surgery for acute aortic dissection type A: results of the German Registry for Acute Aortic Dissection Type A (GERAADA).

BACKGROUND: Cerebral protection during surgery for acute aortic dissection type A relies on hypothermic circulatory arrest, either alone or in conjunction with cerebral perfusion. METHODS AND RESULTS: The perioperative and intraoperative conditions of 1558 patients submitted from 44 cardiac surgery centers in German-speaking countries were analyzed. Among patients with acute aortic dissection type A, 355 (22.8%) underwent surgery with hypothermic circulatory arrest alone. In 1115 patients (71.6%), cerebral perfusion was used: Unilateral antegrade cerebral perfusion (ACP) in 628 (40.3%), bilateral ACP in 453 (29.1%), and retrograde perfusion in 34 patients (2.2%). For 88 patients with acute aortic dissection type A (5.6%), no circulatory arrest and arch intervention were reported (cardiopulmonary bypass-only group). End points of the study were 30-day mortality (15.9% overall) and mortality-corrected permanent neurological dysfunction (10.5% overall). The respective values for the cardiopulmonary bypass-only group were 11.4% and 9.1%. Hypothermic circulatory arrest alone resulted in a 30-day mortality rate of 19.4% and a mortality-corrected permanent neurological dysfunction rate of 11.5%, whereas the rates were 13.9% and 10.0%, respectively, for unilateral ACP and 15.9% and 11.0%, respectively, for bilateral ACP. In contrast with the ACP groups, there was a profound increase in mortality when systemic circulatory arrest times exceeded 30 minutes in the hypothermic circulatory arrest group (P<0.001). Mortality-corrected permanent neurological dysfunction correlated significantly with perfusion pressure in the ACP groups. CONCLUSIONS: This study reflects current surgical practice for acute aortic dissection type A in Central Europe. For arrest times less than 30 minutes, hypothermic circulatory arrest and ACP lead to similar results. For longer arrest periods, ACP with sufficient pressure is advisable. Outcomes with unilateral and bilateral ACP were equivalent.

Efficacy of cut-and-sew box isolation of the posterior left atrium for treatment of atrial fibrillation-long-term follow-up after a modified maze procedure.

BACKGROUND: Box isolation of the posterior left atrium is one surgical or catheter ablative approach for treating atrial fibrillation (AF). In such cases, incomplete transmurality or recovery of pulmonary vein conduction after the application of various ablative techniques is considered the main reason for the recurrence of postprocedural arrhythmia. The use of solely cut-and-sew box isolation does not have these disadvantages and therefore demonstrates maximum efficacy for this therapeutic approach. METHODS: We treated 15 patients with both an indication for open heart surgery and AF (2 paroxysmal, 6 short persistent [<12 months], and 7 long persistent [>12 months] cases) with a solely cut-and-sew box lesion. These patients were then retrospectively followed up over the long term with respect to the end point of freedom of atrial tachyarrhythmias >30 seconds. RESULTS: The median follow-up duration was 42 months (range, 32-84 months). Five (63%) of 8 patients with preoperative paroxysmal or short persistent AF had no arrhythmia recurrence, whereas arrhythmia recurrence was documented in all 7 patients with preoperative long persistent AF. CONCLUSIONS: Despite reliable transmural isolation with cut-and-sew lesions, we observed long-term arrhythmia recurrence in patients who had preoperative paroxysmal or short persistent AF, suggesting that therapy approaches that are more complex than box isolation might be needed for selected patients to achieve long-term stable sinus rhythm, despite the initially paroxysmal or short persistent character of the arrhythmia. A high rate of recurrence in patients with severe structural heart disease and preoperative long persistent AF might indicate that, in general, isolation of the left posterior atrium alone is not an adequate therapeutic approach for these patients.

Analysis of tumor antigen-specific T cells and antibodies in cancer patients treated with radiofrequency ablation.

Radiofrequency (RF) ablation is a minimally invasive technique routinely applied for the treatment of primary and secondary liver tumors. It induces cell death by thermal coagulative necrosis of tumor tissues, whereas cellular metabolism can still take place in a transition zone surrounding the necrotic area. An increase in heat shock protein expression occurs shortly after treatment, suggesting that the induction of activating signals may stimulate the host immune system. In addition, various effects on immune effectors have also been observed, including stimulation of tumor-directed T lymphocytes. Here, we prospectively assessed the activation of tumor antigen-specific antibodies, as well as antigen-specific CD4(+) and CD8(+) T cells in patients suffering from primary or secondary malignancies and treated by RF ablation with or without concomitant chemotherapy. An increase of antibodies (in 4 patients of 49), CD4(+) T cells or CD8(+) T cells (in 2 patients of 49) could be detected several weeks to months following intervention. These findings suggest that in addition to the local control of tumor growth, RF ablation can provide the appropriate conditions for activating tumor-antigen specific immune responses.

Transvenous removal of an entangled central venous line following complex cardiac surgery.

Unintended internal suturing of central venous lines or pulmonary artery catheters in the superior caval vein or the right atrium following cardiac surgery remains a rare but troublesome complication. The line is normally entangled in safety or hemostasis sutures after the removal of the superior caval cannulation. If mild tension is unsuccessful, the patient normally undergoes resternotomy. The objective of this brief communication is to describe of a simple and safe removal method using a transvenous rotational cutting device to divide the hemostasis suture. In order to avoid complicating bleeding, a time delay between initial placement and removal is highly recommended. For extraction, a fully equipped cardiovascular operating room with central venous and arterial lines, attached defibrillator pads, transesophageal echo monitoring, fluoroscopy, and a surgical team, including a heart and lung machine and a perfusionist standby, is mandatory.

Platelets recruit human dendritic cells via Mac-1/JAM-C interaction and modulate dendritic cell function in vitro.

OBJECTIVE: Thrombotic events and immunoinflammatory processes take place next to each other during vascular remodeling in atherosclerotic lesions. In this study we investigated the interaction of platelets with dendritic cells (DCs). METHODS AND RESULTS: The rolling of DCs on platelets was mediated by PSGL-1. Firm adhesion of DCs was mediated through integrin alphaMbeta2 (Mac-1). In vivo, adhesion of DCs to injured carotid arteries in mice was mediated by platelets. Pretreatment with soluble GPVI, which inhibits platelet adhesion to collagen, substantially reduced recruitment of DCs to the injured vessel wall. In addition, preincubation of DCs with sJAM-C significantly reduced their adhesion to platelets. Coincubation of DCs with platelets induced maturation of DCs, as shown by enhanced expression of CD83. In the presence of platelets, DC-induced lymphocyte proliferation was significantly enhanced. Moreover, coincubation of DCs with platelets resulted in platelet phagocytosis by DCs, as verified by different cell phagocytosis assays. Finally, platelet/DC interaction resulted in apoptosis of DCs mediated by a JAM-C-dependent mechanism. CONCLUSIONS: Recruitment of DCs by platelets, which is mediated via CD11b/CD18 (Mac-1) and platelet JAM-C, leads to DC activation and platelet phagocytosis. This process may be of importance for progression of atherosclerotic lesions.

Effect of biopassive and bioactive surface-coatings on the hemocompatibility of membrane oxygenators.

Postoperative complications associated with cardiopulmonary bypass (CPB) surgery and extracorporeal circulation (ECC) procedures are still a major clinical issue. Improving the hemocompatibility of blood contacting devices used for ECC procedures may ameliorate various postpump syndromes. In a simulated CPB model using human blood, we investigated the hemocompatibility, fibrinogen adsorption, and platelet receptor (GPIIb-IIIa) binding capacity of surface-modified membrane oxygenators (Jostra Quadrox). Three groups were compared: (i) biopassive protein coatings (SafeLine), (ii) bioactive heparin coatings (BioLine), and (iii) noncoated controls. During the 2 h recirculation period, plasma concentrations of activation markers for platelets (beta-thromboglobulin), inflammation (elastase), complement (C5a), and coagulation (prothrombin fragment 1+2, thrombin-antithrombin III) were lower in the groups with biopassive and bioactive coatings compared to the noncoated group (p < 0.01). These parameters did not significantly differ between the two surface-coated groups, except for complement activation: C5a levels were higher in the biopassive group compared to the bioactive group (p < 0.01). Moreover, surface-coated oxygenators showed less fibrinogen adsorption, GPIIb-IIIa binding, and platelet/leukocyte adhesion (p < 0.01). We assume that fewer fibrinogen and platelet receptor molecules bound to the surface-coated oxygenator surfaces results in fewer platelet adhesion and activation, which will significantly contribute to the improved hemocompatibility of the biopassive and bioactive oxygenators. Our results suggest that the application of bioactive oxygenators (BioLine) during CPB surgery may reduce postoperative complications for the patient more effectively than biopassive oxygenators (SafeLine).

Gene expression changes in leukocytes during cardiopulmonary bypass are dependent on circuit coating.

BACKGROUND: Cardiopulmonary bypass (CPB) results in a systemic inflammatory response. Leukocytes play a crucial role in inflammatory reactions. Their gene expression profile in the context of CPB is unknown. METHODS AND RESULTS: In a prospective, randomized, and double-blind clinical trial, 12 male patients underwent elective coronary artery bypass grafting with either heparin-coated (group H) or protein-coated (group P) CPB circuits. Oligonucleotide microarray analyses of 22,283 genes were performed on circulating leukocytes, collected immediately before surgery and 6 hours after CPB. Microarray results were validated with real-time polymerase chain reaction. All patients had uneventful surgery, and no significant differences between groups were observed during the clinical course. Multiple statistical analyses with different methods were performed. Compared with preoperative expression at a threshold value of P<0.01, postoperative expression revealed 814 upregulated and 1187 downregulated genes in group H compared with 99 upregulated and 231 downregulated in group P (P<0.001). Fifty genes exhibited a >4-fold increase and 27 exhibited a >4-fold decrease in group H, whereas only 7 genes exhibited upregulation and 7 revealed downregulation in group P. Microarray-pathway-profile-finder analyses determined 1405 upregulated and 1454 downregulated pathways in group H compared with 552 upregulated and 818 downregulated pathways in group P (P<0.01). Pathways related to inflammatory response exhibited highest z scores in group H, reflecting cellular inflammatory activation. CONCLUSIONS: Heparin coating resulted in a more profound alteration in leukocyte gene expression when compared with protein coating. Microarray analyses present an innovative approach for the evaluation and understanding of inflammatory reactions associated with CPB.

Solitary pulmonary nodules: association between signal characteristics in dynamic contrast enhanced MRI and tumor angiogenesis.

PURPOSE: To estimate the association between signal characteristic of dynamic enhanced MRI using curve types and angiogenesis in solitary pulmonary nodules. MATERIALS AND METHODS: Thirty-six patients with a solitary pulmonary nodule (SPN) ranging in size from 6 to 37 mm (median 17 mm) underwent dynamic contrast enhanced MRI with a time interval of 10 s over a total period of 4 min. Resulting from the time-intensity curves four different enhancement curve profiles (A-D) were defined: type A with strong increase followed by early washout, type B with strong increase without washout, type C with slow increase and type D without relevant increase. Maximum peak (Pmax), slope of the first bolus transit (slope) and washout were calculated. Microvessel densities (MVD) were counted at the margins and at the center of the nodules. The mean MVD of each nodule was calculated. Enhancement characteristics were correlated with MVD grouped by diagnosis and by curve types. Curve types were correlated with the score of vascular endothelial growth factor (VEGF). RESULTS: The frequency of malignancy was 55% (20/36). Using curve types for differentiation between malignant and benign SPN, the sensitivity, specificity and accuracy were 100%, 75% and 89%, respectively. The correlation between Pmax and MVD(mean) for all nodules was moderate (r(s)=0.4, P=0.02). A relevant correlation was found between Pmax and MVD(margin) in curve type A (r(s)=0.63; P=0.04) and Pmax and MVD(mean) in curve type C (r(s)=0.86; P=0.006). No positive correlation was found between Pmax and MVD (mean, center and margin) in curve type B. No significant correlation was found for slope and washout. VEGF score correlated positively with curve types (r(s)=0.67; P<0.001). CONCLUSION: A relevant association between perfusion curve profiles and angiogenesis was found in malignant nodules having early washout and in benign lesion with a slow increase of enhancement. In cases of strong signal increase without washout additional factors for enhancement must be considered. The use of curve profiles could allow for the estimation of the extent of VEGF.

Sarcoma of follicular dendritic cells in the dorsal mediastinum.

Follicular dendritic cell sarcomas (FDCSs) are very rare and usually originate in lymph nodes. We report an exceedingly rare case with localization in the dorsal mediastinum and, for the first time, provide positron emission tomography (PET) data for this tumor. This report describes the case of a 76-year-old man with a clinically aggressive tumor in the dorsal mediastinum. Computed tomography scan revealed displacement of soft tissue and lymph nodes. PET showed that the tumor had a high proliferation rate. Investigation of the successfully removed tumor mass revealed reactivity of the tumor cells for follicular dendritic cell markers and desmosomes linking adjacent tumor cells at the ultrastructural level. Marked atypia, a high mitotic rate, and areas of coagulative necrosis were found. The tumor in our case revealed the typical features and thus was classified as FDCS. In contrast to previous reports in the literature, preoperative imaging, histology, and immunohistochemistry studies indicated at least an intermediate degree of malignancy. Nevertheless, the patient made a good postoperative recovery and remained apparently disease-free 2 years later.

Role of apoptosis in myocardial stunning after open heart surgery.

BACKGROUND: Myocardial preservation during open heart surgery is a subject of intense investigation. A prerequisite for further improvement is a better understanding of the underlying pathophysiologic mechanisms responsible for postoperative myocardial stunning. In this report, we analyzed the role of apoptosis in myocardial stunning. METHODS: Myocardial samples were obtained from 11 patients undergoing elective coronary artery bypass grafting before (control) and after cardioplegic arrest and reperfusion. Specimens were examined for apoptosis by electron microscopy, in situ end-labeling of DNA fragments, and biochemically for mitochondrial cytochrome c release. RESULTS: Electron microscopy revealed condensation and margination of nuclear chromatin after surgery, as well as swelling and membrane rupture in mitochondria of single myocytes surrounded by healthy cells. TUNEL-positive cells were also found. Cytochrome c release, an initial step in apoptosis, revealed a 3.4 +/- 0.4-fold increase during surgery (p < 0.0001). Furthermore, cytochrome c release from otherwise intact mitochondria showed a negative correlation with left ventricular function and a positive correlation with the duration of cardioplegic arrest and reperfusion (p < 0.05). CONCLUSIONS: Our data demonstrate that programmed cell death is evident early after open heart surgery and correlates with declining cardiac contractility. We conclude that apoptosis may be an important mechanism in postoperative myocardial stunning.

Hemocompatibility of PMEA coated oxygenators used for extracorporeal circulation procedures.

An inflammatory response to cardiopulmonary bypass (CPB) caused by bioincompatibility of extracorporeal circuits is one of the major clinical issues in cardiac surgery. Recently a new coating material, poly-2-methoxyethylacrylate (PMEA), was developed to improve the biocompatibility of blood contacting surfaces. In a simulated cardiopulmonary bypass model, using fresh human whole blood, 15 membrane oxygenators (Capiox SX18, Terumo Corp., Tokyo, Japan) were compared. Five of them had the PMEA coating, five had a heparin-coated surface, and five had no surface treatment. Blood samples were taken at several time-points during a 90 minute circulation period. Changes in coagulation, complement, and blood cell alteration factors were measured by ELISA methods, plasma bradykinin levels were measured by radioimmunoassay, and expression of genes encoding cytokines TNF-alpha, interleukin-1beta, interleukin-6, and interleukin-8 was determined by semiquantitative real time RT-PCR. Platelet adhesion was significantly reduced in both the PMEA and the heparin coated circuits. Release of platelet activation marker beta-thromboglobulin was significantly higher in the uncoated control group (p < 0.01). After 5 minutes of blood circulation bradykinin levels significantly increased in all three groups (p < 0.01); however, the group with the PMEA coated oxygenators showed the lowest values. Expression of genes encoding proinflammatory cytokines in monocytes was increased in all groups, with the lowest being in the PMEA coated group. PMEA coated CPB surfaces in an in vitro experimental model showed an improved thrombogenicity, reduced bradykinin release, less platelet activation and less proinflammatory cytokines gene expression in comparison with a noncoated group. The authors assume that PMEA coating may ameliorate some of intra- and postperfusion syndromes, particularly hypotension, unspecific inflammation, hyperfibrinolysis, and blood loss.

[Angina pectoris as initial clinical manifestation of ruptured abdominal aortic aneurysm with aortocaval fistula]. / Angina pectoris als klinische Erstmanifestation eines rupturierten Bauchaortenaneurysmas mit aortokavaler Fistel.

CASE REPORT: A 75-year-old patient was hospitalized for angina pectoris and tachycardia. Neither ECG nor laboratory examinations were diagnostic for myocardial infarction. Because of an abdominal thrill and a history of an aortic aneurysm a thoracic and abdominal CT scan was performed. It revealed a rupture of the infrarenal aortic aneurysm into the inferior vena cava. In an emergency operation the aortocaval fistula was closed and the infrarenal aorta including both Aa. iliacae was replaced by a prosthesis. The patient recovered rapidly and was discharged home on the 11th postoperative day. CONCLUSION: Aortocaval fistulas are rare complications of abdominal aortic aneurysms. Due to altered hemodynamics they may become manifest by symptoms usually typical for other diseases. Computed tomography appears to be the most rapid and safe diagnostic measure. Particularly in patients with unstable hemodynamics, surgical transaneurysmatic closure of the fistula together with a prosthetic replacement of the diseased vessel is the therapy of choice.

The challenge to verify ceramide's role of apoptosis induction in human cardiomyocytes--a pilot study.

BACKGROUND: Cardioplegia and reperfusion of the myocardium may be associated with cardiomyocyte apoptosis and subsequent myocardial injury. In order to establish a pharmacological strategy for the prevention of these events, this study aimed to verify the reliability of our human cardiac model and to evaluate the pro-apoptotic properties of the sphingolipid second messenger ceramide and the anti-apoptotic properties of the acid sphingomyelinase inhibitor amitryptiline during simulated cardioplegia and reperfusion ex vivo. METHODS: Cardiac biopsies were retrieved from the right auricle of patients undergoing elective CABG before induction of cardiopulmonary bypass. Biopsies were exposed to ex vivo conditions of varying periods of cp/rep (30/10, 60/20, 120/40 min). Groups: I (untreated control, n = 10), II (treated control cp/rep, n = 10), III (cp/rep + ceramide, n = 10), IV (cp/rep + amitryptiline, n = 10) and V (cp/rep + ceramide + amitryptiline, n = 10). For detection of apoptosis anti-activated-caspase-3 and PARP-1 cleavage immunostaining were employed. RESULTS: In group I the percentage of apoptotic cardiomyocytes was significantly (p < 0.05) low if compared to group II revealing a time-dependent increase. In group III ceramid increased and in group IV amitryptiline inhibited apoptosis significantly (p < 0.05). In contrast in group V, under the influence of ceramide and amitryptiline the induction of apoptosis was partially suppressed. CONCLUSION: Ceramid induces and amitryptiline suppresses apoptosis significantly in our ex vivo setting. This finding warrants further studies aiming to evaluate potential beneficial effects of selective inhibition of apoptosis inducing mediators on the suppression of ischemia/reperfusion injury in clinical settings.