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Lung dysfunction constitutes a severe complication after major cardiac surgery with cardiopulmonary bypass (CPB), substantially contributing to postoperative morbidity and mortality. The current possibilities of preventive and therapeutic interventions, however, remain insufficient. We, therefore, investigated the effects of intraoperative application of the antioxidant and anti-inflammatory green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on CPB-associated lung injury.Thirty piglets (8-15 kg) were divided into four groups: sham-operated and saline-treated control group (n = 7); sham-operated and EGCG-treated control group (EGCG-control group; n = 7); CPB group (n = 10); and CPB + EGCG group (n = 6). The CPB groups underwent 120 min of CPB followed by 90 min of recovery time. In the CPB + EGCG group, EGCG (10 mg/kg body weight) was administered intravenously before and after CPB. Hemodynamic monitoring, blood gas analysis, hematoxylin-eosin staining, and immunohistochemistry of lung tissue were performed.Histologic examination revealed thickening of the alveolar wall and enhanced alveolar neutrophil infiltration in the CPB group (P0.05) compared with those in the control group, which was prevented by EGCG (P0.05). In the CPB group, higher formation of poly(ADP-ribose) and nuclear translocation of apoptosis-inducing factor was detected in comparison with those in the control group (P0.001), which were both reduced in the CPB + EGCG group (P0.001). Compared with the control group, the EGCG-control group showed thickening of the alveolar wall and increased neutrophil infiltration (P0.05).CPB leads to lung edema, pulmonary neutrophil infiltration, and presumably initiation of poly(ADP-ribose) polymerase-dependent cell death signaling in the lung. EGCG appears to attenuate CPB-associated lung injury, suggesting that this may provide a novel pharmacologic approach.

Cardiopulmonary bypass still often is a necessary tool in cardiac surgery in particular in the correction of congenital heart defects in small infants. Nevertheless, among the complications linked to extracorporeal circulation (ECC) with cardiopulmonary bypass (CPB) in both infants and adults one of the most serious problems is renal impairment. Since this might be caused by ischemia/reperfusion injury and accumulation of free radicals, we used (-)-epigallocatechin-3-gallate (EGCG), a derivate from green tea, which is known to possess antioxidant, antiapoptotic and NO-scavenging properties in order to find out whether EGCG may protect the kidney. 23 four-week-old Angler Sattelschwein-piglets (8-15 kg) were divided into three groups: control-group (n=7), ECC-group (n=10), EGCG-group (n=6). The ECC- and EGCG-group were thoracotomized and underwent CPB for 120 min followed by a 90-min recovery-time. The EGCG-group received 10 mg/kg EGCG before and after CPB. Histology revealed that CPB led to widening of Bowman's capsule, and to vacuolization of proximal tubular cells (p

Connexins (Cx) are suggested to play important roles in growth and differentiation. Aim of our study was to investigate the role of endothelial Cx in the angiogenic process. Several parameters of angiogenesis were assessed in 18 h Matrigel in vitro angiogenesis assays with human umbilical vein endothelial cells (HUVEC). Prior to culture on Matrigel cells were treated with nicotine or the gap junction inhibitor palmitoleic acid (PA), or siRNA-knock-down of either Cx37, Cx40 or Cx43 was performed. Changes in Cx expression and their effects on gap-junctional communication were investigated using immunofluorescence microscopy, Western blot and Lucifer Yellow dye transfer. Knock-down of each Cx-isoform significantly reduced the amount of specific Cx protein in HUVEC. Cx-knock-down as well as treatment with PA impaired intercellular communication via gap junctions and diminished significantly the number of capillary branches. Knock-down of Cx43 and Cx40 or treatment with PA reduced complexity pattern in the angiogenesis assay. Nicotine significantly reduced expression of Cx43 and Cx37 as well as average length of capillary branches, number of branches and pattern in the Matrigel assay. We can conclude that connexins are involved in angiogenesis, in particular in branch formation. This can partly explain the changes in angiogenesis seen under nicotine treatment.

Objective Among the complications after cardiac surgery the development of postoperative pulmonary distress is a serious problem. Typically, the patients leave the operating theatre with good blood gas values and O 2 -saturation, but develop their respiratory problems within the next hours/days. We investigated whether extracorporeal circulation may induce biochemical and histological changes in the lungs which may help to explain this development. Methods Piglets (6–10 kg) were anaesthetized using isoflurane and underwent extracorporeal circulation (ECC) with hypothermic (25–28 °C) cardioplegic arrest for 90 min followed by 3 h reperfusion. An additional group received a poly(ADP-ribose) polymerase (PARP)-Inhibitor, INO1001. Cardiopulmonary monitoring was performed during the whole procedure. Finally, lungs were explanted and investigated by histomorphometry and immunohistology for heat shock protein HSP70 (indicator for cellular damage) and TNFα in comparison to normal piglets without ECC. Results Histologically we found significant swelling of the type I alveocytes (thickness increased from 2.4 to 3.2 μm), interstitial oedema, intra-alveolar erythrocyte (4.8 versus 0.4 erythrocytes/alveole) and granulocyte accumulation and fibrinous exudates. There was a significant up-regulation of TNFα and of the cellular repair enzyme HSP70, while in control piglets only minimal levels were observed. INO1001 significantly reduced ECC-induced elevation in TNFα and in HSP70. Despite the dramatic changes after heart-lung-machine (HLM), blood gases and gas transport were almost not affected at that time. Conclusions ECC can lead to early significant histological and histochemical changes which have similarities with a beginning early stage shock lung, although – at 3 h reperfusion – gas transport is still sufficient. INO1001 can partially antagonize these changes.

Objective Closure of ostium secundum atrial septal defects is generally performed by using an interventional approach. We evaluated the outcome of patients requiring secondary surgical therapy. Methods From September 1996 until December, 2005, 418 patients received interventional and 297 patients underwent surgical closure of an ostium secundum atrial septal defect at our center. Another 15 patients (local, 5; regional, 5; and national, 5 referrals) had complications after occluder placement, and they form the study population. Results Indications for surgical repair in these 15 patients were dislocation of the occluder in 5, neurologic events after occluder placement in 5, residual defects in 4, and sepsis with questionable occluder infection in 1 patient. A total of 7 patients had neurologic events, 5 of embolic origin. The interval between interventional occluder placement and definitive surgical repair was 319 ± 416 days (median 123 days; range 0–1395 days). Patient age at operation was 34.9 ± 18.6 years. Nine patients were operated on via an anterolateral minithoracotomy, and 6 received a conventional sternotomy. One patient with sepsis underwent abdominal surgery on postoperative day 1 and subsequently died of multiorgan failure; there was no proof of occluder endocarditis. At 2.2 ± 1.9 years of follow-up, all other patients had returned to full-time work without residual neurologic impairment. Conclusions Complications may arise after interventional ostium secundum atrial septal defect closure. This must be evaluated against the extremely low risk of a standard surgical closure. The functional outcome after secondary surgical ostium secundum atrial septal defect closure with removal of an occluder system is excellent.

Objective Reoperations are associated with an increased surgical risk due to adhesions. We prospectively evaluated a bioresorbable membrane after surgery for congenital heart defects over a 3.5-year period. Methods The surgical membrane (CV Seprafilm, Genzyme, Cambridge, Mass) was applied in 350 of 1024 patients; 30 of them underwent reoperation and were evaluated in comparison to 10 random reoperated patients. Adhesions were evaluated using a subjective scoring system [1 (lowest tenacity) to 5 (highest tenacity)] and extent in percent at different regions of the heart. Results Patients were operated for atrioventricular septal defect (69), tetralogy of Fallot (65), functional single ventricle (75), valve surgery (48), ventricular septal defect (20), subaortic stenosis (17), hypoplastic left heart syndrome (17), and other diagnoses (39). Application of the surgical membrane was safe in all patients, without any infections. At reoperation patients received Glenn (14), total cavopulmonary connection (6), and others (10). Overall mortality was 2/350 (0.57%). There was a remarkable reduction in tenacity score (3.3 vs 4.3) and in the extent of adhesions (77.7% vs 86%). Duration of reoperation was significantly reduced. Conclusions A bioresorbable surgical membrane leads to a significant reduction in the tenacity and amount of adhesions. It is recommended for general use whenever repeat operation is anticipated in congenital as well as in adult cardiac surgery.

Background The aim of the present study was to evaluate the current outcome and reoperation rate after applying a one-stage correction strategy for interrupted aortic arch (IAA) with ventricular septal defect (VSD) and also for aortic coarctation and hypoplastic aortic arch (CoA-HyAA) with VSD beginning September 1999. Methods Twenty-four consecutive patients with IAA (n = 12) or CoA-HyAA (n = 12) with VSD underwent early one-stage correction. Patients' mean age was 12 days (range, 2 to 188); mean weight was 3.6 kg (range, 2.1 to 7.3), 6 patients were less than 2.5 kg. Three IAA were type A, 5 type B1, 3 type B2, and 1 type C. Associated anomalies included a large VSD in all, left ventricular outlet tract obstruction in 5, transposition of the great arteries, aortopulmonary window, persistent truncus arteriosus, and double-outlet right ventricle in 1 patient. Selective brain perfusion through innominate artery and selective coronary perfusion through aortic root during aortic arch reconstruction was used in all patients. Mean follow-up was 2.2 ± 0.9 years. Results There was no early, no late mortality, and no postoperative neurologic complications. Mean crossclamp duration was 72 ± 32 minutes, lowest temperature 22.8 ± 4°C and selective brain and coronary perfusion duration was 34 ± 13 minutes. Eighteen patients required delayed sternal closure at 1.7 days postoperatively. New perioperative management reduced the overall morbidity. Four patients after IAA plus VSD repair developed aortic arch restenosis and were successfully treated by balloon dilatation. One patient with d-TGA underwent right ventricular outflow tract reconstruction of right ventricular outlet tract obstruction 7 months after the initial repair. Pressure gradients across the anastomosis at most recent follow up were less than 10 mm Hg. All patients are asymptomatic and are developing normally. Conclusions One-stage complete correction is feasible in newborns with aortic arch obstruction with VSD. Complex cardiac anatomy presents no additional risk for the procedure. The early one-stage correction yields excellent surgical results and good functional outcome.

This study was undertaken to evaluate the antiadhesive properties of a polymeric agent in infants undergoing staged surgical correction of congenital heart abnormalities.Sixteen infants having staged surgical repair were treated with a polymeric matrix at the completion of the initial surgery. There were 5 untreated controls. The tenacity and extent of adhesions at five separate regions of the heart were evaluated at the follow-up surgery.For all sites combined, there was a threefold difference in median tenacity scores in favor of the experimental treatment (1.0 vs 3.0, p0.01). Significant differences were achieved separately at the right ventricle and the anterior surface of the great vessels (p = 0.02 for both comparisons). Analysis of adhesion scores reflecting the extent of adhesions similarly favored the experimental treatment for all sites (80 vs 270, p0.01), with significant differences persisting at the right atrium (p0.01) and the anterior surface of the great vessels (p = 0.04). There were no treatment-related adverse events.Use of this polymeric agent at the completion of open cardiac surgery may prevent the occurrence or reduce the severity of pericardial adhesions.

Background Surgical closure of secundum atrial septal defect (ASD) is a standard procedure associated with very low mortality and morbidity. We evaluated outcomes in the era of catheter-based interventional closure and minimally invasive techniques. Methods From May 1996, February 2002, 177 patients with a body weight of more than 30 kg underwent surgical ASD closure. A right lateral minithoracotomy (LMT) was used in 122 patients and a conventional approach, in 55. Diagnoses included secundum ASD in 106 patients in the LMT group and 40 in the conventional group, sinus venosus ASD in 13 patients in each group, and status post interventional closure in 3 and 2 patients, respectively. Mean age was 37 ± 17 years in the LMT group and 43 ± 20 years, in the conventional group and mean body weight was 66 ± 17 kg and 70 ± 16 kg, respectively. In the LMT group, femoral cannulation was performed for cardiopulmonary bypass. Results Direct ASD closure was carried out in 67.2% of patients in the LMT group and 58.2% of those in the conventional group. The remaining patients had pericardial patch closure. There was one death: A patient in the conventional group who required explantation of an Amplatzer device because of infection died postoperatively. Average stay in the intensive care unit was 1.2 ± 0.5 days. Two patients required reoperation for residual ASD after direct closure; 1 sustained a temporary neurological deficit that resolved completely. On postoperative echocardiography, a minimal residual shunt was seen in only 3 patients. All patients were in good clinical condition with improved functional status at discharge from the hospital. Conclusions Secundum ASD closure by LMT has become as standard and safe an operation as the conventional technique and achieves good perioperative results and satisfactory long-term outcomes. Thus LMT is an attractive option for patients who are not suitable for closure using catheter-based devices.

We are describing a most unusual variant of aortic arch interruption. The ascending aorta was atretic above the sinutubular junction forming a blind-ending pouch. The coronary arteries were the only vessels arising from the aortic trunk. All the brachiocephalic vessels were perfused in retrograde fashion through the arterial duct. The aortic valve itself was dysplastic, stenotic, and permitted severe regurgitation. There was no subaortic obstruction. A modified first stage Norwood palliation was performed. Due to myocardial insufficiency transthoracic extracorporeal membrane oxygenation had to be commenced at the end of surgery. Unfortunately the child died due to severe intracranial hemorrhage.

A 6-week-old patient weighing 4 kg was admitted for surgical correction of anomalous left coronary artery from the pulmonary artery. Reimplantation of the coronary artery with cardiopulmonary bypass was impossible because the patient also had hereditary spherocytosis, which put him at risk for hemolytic anemia. Thus, closure of the left main stem and left internal mammary artery-left anterior descending coronary artery bypass grafting were performed successfully with the heart beating.

atrioventricular septal defect and microdeletion 22q11 Christian Paech ⁎, Martin Kostelka , Matthias Grothoff c a Heart Center, University of Leipzig, Strumpellstrasse 39, 04289 Leipzig, Germany b Department for Cardiac Surgery, University of Leipzig, Heart Center, Strumpellstr. 39, 04289 Leipzig, Germany c Department for Diagnostic and Interventional Radiology, University of Leipzig, Heart Center, Strumpellstr. 39, 04289 Leipzig, Germany