Effect of Allopurinol Pretreatment on Free Radical Generation after Primary Coronary Angioplasty for Acute Myocardial Infarction

Abstract

Allopurinol, an inhibitor of xanthine oxidase, was shown to improve the regional ventricular function after coronary artery occlusion and reperfusion in animal models. The effects of oral administration of allopurinol on a transient increase in free radical generation after primary percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI) and on their clinical outcomes were examined. Thirty-eight AMI patients undergoing primary PTCA were randomly assigned to control (group 1, n = 20) and allopurinol treatment groups (group 2, n = 18). Allopurinol (400 mg) was administered orally just after the admission (approximately 60 min before reperfusion). Free radical production was assessed by successive measurement of urinary excretion of 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) after PTCA. Urinary 8-epi-PGF(2alpha) excretion was increased by twofold at 60-90 min after PTCA compared with the baseline value in group 1. This increase was completely inhibited in group 2. Plasma allopurinol concentration was 1,146 +/- 55 ng/ml in group 2 when reperfusion was achieved. Slow flow in the recanalized coronary artery after PTCA occurred less frequently in group 2 than in group 1. Cardiac index determined just after reperfusion and left ventricular ejection fraction at 6 months after PTCA were both significantly greater in group 2 than in group 1 although pulmonary capillary wedge pressure was similar in the two groups. In conclusion, allopurinol pretreatment is effective in inhibiting generation of oxygen-derived radicals during reperfusion therapy and the recovery of left ventricular function in humans.

Nitroso–Redox Interactions in the Cardiovascular System

“…105 In a study of 38 patients with acute MI, patients were randomly assigned to receive allopurinol or not before primary angioplasty. 106 Not only were slow-flow phenomena less frequent in the allopurinol group, but cardiac index measured immediately after PTCA and ejection fraction at 6 months were significantly greater in treated patients. 106 …”

“…106 Not only were slow-flow phenomena less frequent in the allopurinol group, but cardiac index measured immediately after PTCA and ejection fraction at 6 months were significantly greater in treated patients. 106 …”

A cell-based approach to study changes in the pancreas following nicotine exposure in an animal model of injury

“…We have also used the noncytotoxic nicotine dose of 100 μM based on our earlier published study [4]. The 8.5-μM dose of allopurinol used in our study was calculated based on the plasma levels obtained in a study of acute myocardial infarction [39].…”

Gout, Hyperuricemia, and the Risk of Cardiovascular Disease: Cause and Effect?

“…The role of oxidative stress secondary to XO in ischemia-reperfusion injury has also been addressed in several clinical trials in humans. Guan et al [27] found that patients receiving allopurinol prior to reperfusion during coronary angioplasty had improved left ventricular function that was significant 6 months after the procedure.…”