Endothelial Dysfunction after Open Heart Surgery : Role of Oxygen Free Radical and Lipid Peroxidation in Reperfusion Injury

ABSTRACT

BACKGROUND: Reperfusion of ischemic myocardium is clinically encountered during thrombolytic therapy of acute myocardial infarction, percutaneous transluminal coronary angioplasty(PTCA), and coronary artery bypass graft(CABG). Reperfusion results in endothelial dysfunction characterized by a reduced release of endothelium-derived relaxing factor(EDRF) in animal studies. Studies with experimental animals have emphasized the role of oxygen free radicals and lipid peroxidation in pathophysiology of reperfusion injury and myocardial stunning. The object of this study is to determine whether endothelial dysfunction was developed after open heart surgery and to evaluated the role of oxygen free radical and lipid peroxidation in reperfusion injury. METHODS: The study group was comprised 13 patients who underwent open heart surgery(male/female 2/11, mean age 43+/-4 year, Atrial septal defect in 4, Ventricular septal defect in 1, Mitral regurgitation in 2, Tetralogy of Fallot in 1, and Aortic stenosis and Regurgitation with Mitral stenosis in 5 patients). The endothelial function was evaluated with the vasomotor response to acetylcholine and nitroglycerin by change of arterial diameter during the continous infusion of acetylcholin, from 10(-9) to 10(-6) molar concentration to the coronary artery and intracoronary injection of 200microg nitroglycerin after acetylcholine infusion. The infusion study was performed before and 10 days after surgery. For analysis of the role of oxygen free radical and lipid peroxidation in reperfusion injury, blood samples for malondialdehyde and neutrophil respiratory burst test(hydrogen peroxide amount of neutrophils) were obtained in pre-declamping of aorta and 5 min, 10 min, and 20 min after declamping of aorta from coronary sinus. RESULTS: 1) The vasoconstrictor response to acetylcholine, 10(-9) to 10(-6)M concentration, at proximal and distal left anterior descending coronary artery, were increased significantly in post-operation infusion study but there was no singnificant difference in vasodilator response to nitroglycerin. 2) The mean absorbance value of malondialdehyde(MDA) in pre-declamping and 5min, 10min, and 20min after reperfusion were 96+/-12, 73+/-12, 89+/-11 and 77+/-12, respectively. There was no significant difference in plasma MDA level and hydrogen peroxide amount of neutrophils after reperfusion(aortic declamping). CONCLUSION: These data suggest that endothelium dependent vascular relaxation is impaired in patients with open heart surgery and post-ischemic reperfusion injury may be responsible for the abnormal response. But we did not determine the role of lipid peroxidation and oxygen free radical in reperfusion injury.