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Background Free radicals formed during ischemia and reperfusion can lead to lipid peroxidation (LPO) and the formation of 4-hydroxy-2-nonenal (4-HNE), one of the most toxic products of LPO. Using a heterotopic rat heart transplantation model we investigated endogenous 4-HNE formation as a response to cold storage of the transplant and warm blood reperfusion in the recipient. Methods Lewis rat hearts were subjected to 30, 240 or 480 minutes of 4°C cold ischemia in Bretschneider cardioplegic solution without or with transplantation and 240-minute reperfusion in F344 recipients. The amount of 4-HNE modified proteins was quantified in rat heart cryosections with an antibody recognizing cysteine-, histidine- and lysine-4-HNE Michael adducts and image analysis of immunostained tissue. Results We detected 4-HNE-modified proteins in ischemic rat hearts after transplantation and reperfusion. In hearts submitted to ischemia only, 4-HNE-protein adducts comprised 0.7 ± 0.3% (30 minutes), 0.7 ± 0.4% (240 minutes) and 0.2 ± 0.1% (480 minutes) (mean ± SEM) of the tissue area. Transplantation and reperfusion in the recipient significantly increased the amount of protein adducts to 6.8 ± 2.6% (p = 0.041), 5.2 ± 1.4% (p = 0.009) and 5.7 ± 0.9% (p = 0.002) in 30-, 240- and 480-minute ischemic hearts, respectively. Conclusions Under the conditions applied in the present study, cold ischemia for >30 minutes did not significantly alter the amount of 4-HNE protein adducts. However, because after transplantation and reperfusion, 6% of heart tissue consisted of 4-HNE-modified proteins, it can be assumed that this damage negatively affects long-term survival of the transplant

Background Tissue damage caused by reactive oxygen species (ROS) formed during ischemia/reperfusion seems to be an important risk factor in the failure of transplanted hearts. Although endogenous anti-oxidants protect the myocardium against free radical attack under physiologic conditions, their capacity may become limited during severe oxidative stress. Thus, we investigated the effect of 8-hour cold ischemia on the myocardial anti-oxidative defense system in a heterotopic rat heart transplantation model. Methods Lewis rat hearts were subjected to 30 or 480 minutes of 4°C cold ischemia in Bretschneider cardioplegic solution with or without transplantation and reperfusion (30 or 240 minutes) into F344 recipients. Activity levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S -transferase (GST), and concentrations of glutathione (GSH), glutathione disulfide (GSSG) and lipid hydroperoxides (LOOH) were analyzed in heart homogenates. For histology, cross-sections of the ventricles were stained with hematoxylin-eosin. Results Except for GST, enzyme activities and GSSG concentration increased and the glutathione redox ratio (GSH/GSH + 2GSSG) significantly decreased in 480-minute ischemic hearts compared with those with 30-minute ischemia. Reperfusion dramatically decreased both GSH and GSSG and increased LOOH formation but without severe histopathologic findings in the transplants. Applying a tree-structured classifier technique, GSH and LOOH were identified as significant features indicative of transplantation-induced oxidative stress. Conclusions In the present study severe loss of glutathione and formation of LOOH indicated transplantation-induced oxidative stress in the rat heart; therefore, alterations of these parameters may hint at relevant deficits in the myocardial anti-oxidative defense and may also predict subsequent tissue damage.

Polymorphisms in the CYP2C9 gene can have a significant impact on drug therapy by affecting the pharmacokinetics of frequently prescribed drugs, such as phenprocoumon and warfarin. It is essential therefore that genetic CYP2C9 variants are excluded in patients with a suspected intolerance of anticoagulant therapy. Here we present the first report of a case of left ventricular non-compaction syndrome associated with a genetic variant of the CYP2C9 gene in a 45-year-old woman with myocardial insufficiency who was scheduled for implantation of a cardioverter defibrillator.

Three biopsies were taken transmurally in different time intervals (before and after ischemia and during the reperfusion phase) from 20 patients undergoing open-heart operation for acquired valvular heart disease, and the myocardial cylinders were examined with the electron microscope. They were scrutinized to see if there is a relationship between the degree of hypertrophy and degeneration before ischemia and the extent of ischemic damage after a certain ischemia period, and between the damage before ischemia and the postoperative outcome of the patients. Our results show that the ischemic changes are not dependent on the preischemic extent of hypertrophy and degeneration. It seems that they are mainly dependent on the duration of ischemia because the degree of ischemic damage increases with prolongation of the ischemia interval. However, a good correlation was found between the preischemic changes and the postoperative outcome. Especially the combination of marked hypertrophy and the appearance of degenerative signs in the biopsy taken before ischemia seems to predestine a bad postoperative course. Therefore, it can be concluded that the total damage to the myocardial cells, which results from the sum of previous damage (hypertrophy and degeneration) and ischemic alterations, is responsible for the postoperative outcome.

Between 1972 and 1976, 24 patients have been treated by open pulmonary embolectomy with the aid of cardiopulmonary bypass (CPB). In 17 (71 percent) acute pulmonary embolism occurred 3 to 60 days after a surgical procedure. The remaining seven (29 percent) patients had chronic medical diseases. The interval between clinical manifestation of acute pulmonary embolism and the performance of open embolectomy ranged from 8 to 36 hours. The definitive diagnosis in all patients was made by pulmonary arteriography. Candidates for pulmonary embolectomy were selected by assessment of hemodynamic studies: shock, arterial PO2 less than 65 mm. Hg, acidosis, pulmonary artery pressure higher than 20 to 30 mm. Hg, and central venous pressure elevated (patients in Class III or IV according to the Greenfield classification). The definitive indication for embolectomy was occlusion of the main pulmonary artery of more than 50 percent as well as occlusion of the right or left pulmonary artery. Of the seven patients operated upon between 1973 and 1974, three (43 percent) died in the early postoperative period. Between 1975 and 1976 the operative mortality rate in 17 patients was 23 percent (four patients). Our results show that prompt diagnosis of acute massive pulmonary embolism and better selection of patients may improve significantly the survival rate after open pulmonary embolectomy with CPB.