title: 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.
authors.affiliation: Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.
authors.forename: Weiping
authors.initials: W
authors.lastname: Guan
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osanai
authors.forename: Takaatsu
authors.initials: T
authors.lastname: Kamada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hanada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishizaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Onodera
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iwasa
authors.forename: Norio
authors.initials: N
authors.lastname: Fujita
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kudo
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
mesh_terms: 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
chemical_list: D028441:F2-Isoprostanes; D016166:Free Radical Scavengers; D005609:Free Radicals; C075750:8-epi-prostaglandin F2alpha; D000493:Allopurinol; D015237:Dinoprost; D010117:Oxypurinol