Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction.
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.
Guan
Weiping
W
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.
Osanai
Tomohiro
T
Kamada
Takaatsu
T
Hanada
Hiroyuki
H
Ishizaka
Hiroshi
H
Onodera
Hiroyuki
H
Iwasa
Atsushi
A
Fujita
Norio
N
Kudo
Shigeaki
S
Ohkubo
Tadashi
T
Okumura
Ken
K
D000284:Administration, Oral; D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015906:Angioplasty, Balloon, Coronary; D015237:Dinoprost / Q000031:analogs & derivatives*; D004562:Electrocardiography; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D010117:Oxypurinol / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects
D028441:F2-Isoprostanes; D016166:Free Radical Scavengers; D005609:Free Radicals; C075750:8-epi-prostaglandin F2alpha; D000493:Allopurinol; D015237:Dinoprost; D010117:Oxypurinol