Brief Antecedent Ischemia Attenuates Platelet-Mediated Thrombosis in Damaged and Stenotic Canine Coronary Arteries

Abstract

Background —Recent studies suggest that patients with angina before myocardial infarction exhibit improved recovery of coronary perfusion after thrombolysis by an as-yet-unknown mechanism. We therefore proposed that brief antecedent ischemia/reperfusion may, via release of adenosine, improve vessel patency in damaged and stenotic coronary arteries. Methods and Results —Anesthetized dogs underwent coronary injury+stenosis, resulting in repeated cyclic variations in coronary blood flow (CFVs) caused by the formation/dislodgment of platelet-rich thrombi. Vessel patency was assessed for 3 hours after stenosis by quantification of the nadir of the CFVs, duration of total thrombotic occlusion (flow=0), and area of the flow-time profile (expressed as percent of baseline flow×180 minutes). In protocol 1, dogs received 10 minutes of coronary occlusion+10 minutes of reflow or a comparable 20-minute control period before injury+stenosis. The median nadir of the CFVs was higher (4.0 versus 0.3 mL/min), median zero flow duration per 30-minute time interval was shorter (0.4 versus 15.1 minutes), and mean percent flow-time area was greater (54±8% versus 28±9%) in dogs that received antecedent ischemia versus controls ( P <.05). These benefits of antecedent ischemia/reperfusion were largely mimicked by a 10-minute intracoronary adenosine infusion (400 μg/min) in lieu of brief ischemia (protocol 2) and were abolished by administration of the adenosine A 1 /A 2 receptor antagonist PD 115,199 (3 mg/kg IV) before brief antecedent coronary occlusion (protocol 3). Conclusions —Brief antecedent ischemia attenuates subsequent platelet-mediated thrombosis in damaged and stenotic canine coronary arteries, due, in large part, to an adenosine-mediated mechanism.