C. Selim Isbir

Association Between Angiotensin-Converting Enzyme Gene Polymorphism and Coronary Artery Disease

An insertion/deletion (I/D) polymorphism in the gene for angiotensin‐converting enzyme (ACE) is associated with myocardial infarction and other cardiac pathology. There is evidence for a role of the renin‐angiotensin system in cell growth and in the repair of damaged arterial walls, so the ACE gene is postulated to be a candidate gene affecting the important clinical problem of coronary artery disease (CAD). In view of the clinical importance of the ACE as a major marker of cardiovascular diseases, we investigated the I/D polymorphism of the ACE gene in Turkish CAD patients in comparison with control subjects to evaluate a possible association between CAD and the gene encoding ACE. Polymerase chain reaction, restriction fragment length polymorphism, and agarose gel electrophoresis techniques were used to determine the ACE genotype in 58 subjects. The frequencies of ACE D and ACE I allele among the patients with CAD were 62.26% and 37.73% and in the control subjects were 49.3% and 50.76%, respectively. The greater frequency of deletion allele (D) was in the CAD group than in the control subjects was significant (P < 0.01).

Ischemic preconditioning and nicotinamide in spinal cord protection in an experimental model of transient aortic occlusion.

OBJECTIVES Spinal cord injury is a devastating complication after aortic surgery. The aim of the present study is to examine the effects of ischemic preconditioning (IPC) and nicotinamide containing perfusate in transient aortic occlusion in the rat. METHODS Thirty-two male Spraque-Dawley rats under general anesthesia were randomly assigned to four groups (n=8 in each group). The infrarenal aortas were clamped for 45 min. Groups were as follows: Group 1, undergoing occlusion but receiving no treatment. Group 2, had 5 min of IPC before occlusion. Group 3, received nicotinamide (0.2 ml/l) during the transient occlusion. Group 4, received combined IPC (5 min) and nicotinamide infusion during the transient occlusion. The rats were then allowed for recovery and were tested for their neurological status. All animals were sacrificed at the end of the 48 h and spinal cords also examined histologically. Anti- poly (ADP-ribose) polymerase p85 fragment pAb was used as an immunohistochemical marker for detection of apoptosis. RESULTS In 24 h paraplegia represented as grade 0 and 1 occurred in six animals in Group 1 and two animals in Groups 2 and 3 and one in Group 4. In 48 h six animals in Group 1 and only one animal in Groups 2 and 3 showed a paraplegia. The incidence of neurologic deficit was significantly reduced in animals who had IPC and nicotinamide infusion (P<0.05). At 48 h, combined IPC and nicotinamide showed a significant benefit compared to nicotinamide but not to the IPC alone. Histologic examination of the spinal cords revealed that a neuronal necrosis contributes to acute spinal cord degeneration after a period of aortic occlusion and both nicotinamide and IPC have protective effects against neuronal necrosis. No difference was found among the groups. CONCLUSIONS Both IPC and nicotinamide are beneficial in protection against neurological damage in transient aortic occlusion. IPC alone as expected is significantly beneficial both at 24 and 48 h compared to controls. At 24 h combined nicotinamide and IPC show significant benefit compared to only nicotinamide, but this difference is not maintained at 48 h.

Coronary artery bypass surgery in patients with severe left ventricular dysfunction

OBJECTIVE The role of coronary artery bypass grafting (CABG) in patients with severe left ventricular dysfunction was evaluated. METHODS Two hundred and twelve patients (152 men, 60 women; age 35 to 82, mean 55) with ejection fraction (EF) of less than 30% underwent CABG between January 1996 and February 2001 by a single surgeon (SA). They compromised of 12% of 1759 patients operated on in this period. EF ranged from 17% to 30% (mean 25%). Preoperatively 68% had congestive heart failure and 72% had severe angina (CCS 3 or 4). A left main lesion was found in 26% of the cases. The mean number of grafts was 3.18 per patient. The left internal mammary artery (LIMA) was used on 107 patients (50.4%). Preoperative intraaortic balloon pump (IABP) was used on 32 patients (15%). Endarterectomy was performed on 53 patients (25%). The patients were followed for up to 58 months (mean 28.7). RESULTS Twelve patients died in hospital (5.6%). Survival was 94%, 87%, 80% and 73% at 1, 2, 3 and 4 years respectively. Among the preoperative variables survival was negatively affected by chronic renal failure, older age, congestive heart failure, elevated pulmonary artery pressure and recent myocardial infarction, by means of multivariate analysis. Preoperative IABP support improved the operative mortality significantly (P=0.002). Use of LIMA did not have any influence on survival. CONCLUSION CABG on patients with poor left ventricular function: (1). Can be performed with an acceptable mortality. (2). Mid term results are encouraging. (3). Preoperative IABP support improves the chance of survival.

Results of Adjunctive Coronary Endarterectomy in 548 Patients

Coronary endarterectomy is a controversial procedure that plays a particular role in the treatment of coronary artery disease. We retrospectively investigated the results for 548 patients who underwent coronary endarterectomy as an adjunctive therapy for coronary artery bypass graft surgery during the period between 1996 and 2004. We assessed short-term outcomes and identified risk factors for adverse outcomes. Mean patient age was 67.9 + 9.3 years and mean angina class was 2.7 + 0.3. The mean number of distal anastomoses was 3.8 + 1.1 patients (73.4%) had single and 151 (27.6%) multiple coronary artery endarterectomies. Of the 151 patients who underwent multiple endarterectomies, 97 (17.7%) had endarterectomies in 2 coronary arteries, 40 (7.2%) in 3 coronary arteries, 11 (2%) in 4 coronary arteries, 2 (0.36%) in 5 coronary arteries, and 1 (0.18%) in 6 coronary arteries. Postoperative mortality was 6.2% (34 patients). The predictors for early mortality were recent myocardial infarction and left ventricular dysfunction. Our results suggest that adjunctive coronary endarterectomy can be accomplished with acceptable results but with higher mortality rates than ordinary coronary artery bypass grafting. Adjunctive coronary endarterectomy should be considered as a last option for the surgical treatment of diffuse coronary disease.

The effect of captopril on membrane bound enzymes in ischemia–reperfusion injury

There is substantial evidence that Na(+)K(+)/Mg(2+) ATPase and Ca(2+)/Mg(2+) ATPase enzymes would effect the membrane integrity. Forty guinea pig (n=10 in each group) hearts were studied in an isolated Krebs-Henseleit solution perfused Langendorff cardiac model. The first group was utilized as the control group. Group 2 hearts were arrested with captopril (200micromol/l) added St Thomas Hospital Cardioplegic Solution (STHCS). Group 3 animals were pretreated with oral captopril (0.3mg/kg/twice a day) for 10days and then arrested with STHCS. Group 4 hearts were again pretreated with oral captopril (0.3mg/kg/twice a day for 10days) arrested with STHCS and reperfused with captopril added Krebs-Henseleit solution (200micromol/l). Hearts were subjected to normothermic global ischemia for 90min and than were reperfused at 37 degrees C. When the treated groups were compared with control, best results were achived by group 4. The Na(+)K(+) and Ca(2+)/Mg(2+) ATPase levels increased from 466.38+/-5.99 to 564.13+/-7.77 and 884.69+/-9.13 to 1254.29+/-5.75 nmol Pi/mg/prot/h respectively (P<0.05). These results suggest that captopril protects the membrane integrity and thus played a role at the recovery of depressed membrane bound Na(+)K(+)/Mg(2+) ATPase and Ca(2+)/Mg(2+) ATPase activity and also in ischemia-reperfusion injury.

The effect of enalapril maleat in ischemia reperfusion injury: Possible role of membrane bound enzymes

The present study evaluates the protective effect of enalapril maleat on myocardial ischemia-reperfusion injury. Membrane bound enzymes; Na+K+/Mg2+ ATPase and Ca2+/Mg2+ ATPase are known to regulate the membrane integrity. We hypothesized that if we could protect the cell membrane in ischemia-reperfusion period, we might have a chance to augment contractility. Thirty-two Guinea pig hearts were studied in an isolated Krebs-Henseleit solution-perfused Langendorff cardiac model. In Group 1, control hearts (n=8) were arrested with St. Thomas Cardioplegic Solution (STHCS) alone. In Group 2 (n=8), animals were pretreated with oral enalapril maleat (0.2mg/kg/daily) for ten days and arrested with STHCS. In Group 3, (n=8) the hearts were arrested with enalapril maleat- (1 µmol/L) added STHCS. In Group 4 (n=8), the hearts were again pretreated with oral enalapril maleat for ten days and then reperfused with enalapril maleat-added Krebs-Henseleit solution. Hearts were subjected to normothermic global ischemia for 90 minutes and then were reperfused at 37°C. The study groups showed better recovery of left ventricular systolic function. In terms of biochemical determinations, best results were achieved at Group 4. The Na+K+ ATPase and Ca2+ ATPase levels were measured at 466.38 ± 5.99 to 545.23 ± 8.79, and 884.69 ± 9.13 to 1254.34 ± 1.56, respectively (p<0.05). Based on these results, it can be concluded that enalapril maleat protects the membrane integrity and thus plays a role in restoring the contractility in ischemia-reperfusion injury.