From the Heart Institute, Good Samaritan Hospital and Department of
Medicine, Section of Cardiology, University of Southern California, Los
Angeles.
Correspondence to Karin Przyklenk, PhD, Heart Institute/Research, Good Samaritan Hospital, 1225 Wilshire Blvd, Los Angeles, CA 90017-2395.
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
flowx180 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 A1/A2
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.
© 1998 American Heart Association, Inc.
Basic Science Reports
Brief Antecedent Ischemia Attenuates Platelet-Mediated Thrombosis in Damaged and Stenotic Canine Coronary Arteries
Role of Adenosine
Key Words: adenosine • ischemia • stenosis • thrombosis • platelets
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