title: Beneficial effects of oxypurinol pretreatment in stunned, reperfused canine myocardium.
abstract: The mechanism of reperfusion induced injury in acutely ischaemic myocardium is controversial but may be connected with oxygen free radical generation. However, chronic allopurinol treatment has beneficial effects in ischaemic myocardium which are not due to its inhibition of xanthine oxidase induced oxygen free radical production. Allopurinol is rapidly metabolised to oxypurinol, so we have examined the effects of this compound on nutrient blood flow and contractility in a canine model of stunned, reperfused myocardium. Twenty anaesthetised dogs underwent 15 min of total circumflex artery occlusion followed by 15 min restricted reflow and 2 h full reflow. Posterior wall thickening was determined by sonomicrometry and expressed as % control function. Regional myocardial blood flow was measured by microsphere technique and expressed in ml.min-1.g-1. Dogs in the treatment group (n = 10) received 25 mg.kg-1 oxypurinol as a 5 min left atrial infusion, 15 min prior to circumflex occlusion. Controls (n = 10) received a saline infusion. During occlusion mean circumflex pressure (17.6 v 18.2 mm Hg), endocardial flow [0.02(SEM 0.01) v 0.03(0.01) ml.min-1g-1], and area at risk [31.4(1.2%) v 34.6(2.4%)] were similar for both groups (control v treated respectively). Endocardial blood flow increased following acute administration of oxypurinol: 1.57(0.15) v 0.92(0.15) ml.min-1g-1 in control (vehicle) group, p less than 0.05. This effect persisted for the duration of the experiment, with a significant increase during early reflow: 1.83(0.32) v 0.74(.21), p = 0.03. There was also a marked increase in posterior wall function in the treated group, at 54.6(5.5)% v 5.1(8.4)% in the control group (p = 0.0003). These results show that pretreatment with oxypurinol protects acutely ischaemic myocardium, producing enhanced myocardial blood flow, diminished systolic bulge during occlusion, and markedly enhanced function recovery following reperfusion.
authors.affiliation: Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
authors.forename: H H
authors.initials: HH
authors.lastname: Holzgrefe
authors.forename: J K
authors.initials: JK
authors.lastname: Gibson
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D001794:Blood Pressure; D003326:Coronary Circulation; D003971:Diastole; D004285:Dogs; D006339:Heart Rate; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010117:Oxypurinol / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D013599:Systole
chemical_list: D011743:Pyrimidines; D010117:Oxypurinol