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(Circulation. 2000;102:88.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Brief Antecedent Ischemia Enhances Recombinant Tissue Plasminogen Activator–Induced Coronary Thrombolysis by Adenosine-Mediated Mechanism

Karin Przyklenk, PhD; Peter Whittaker, PhD

From the Heart Institute, Good Samaritan Hospital, and the Department of Medicine, 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. E-mail karinp{at}dnamail.com

Background—Clinical studies have implicated preinfarct angina (brief antecedent ischemia/reperfusion [I/R]) as a predictor of more rapid thrombolysis and lower rates of reocclusion. However, the effects of antecedent ischemia on the efficacy of thrombolysis have not been rigorously assessed. Using a canine model of coronary thrombosis, we aimed to (1) reproduce these clinical findings and (2) determine whether release of adenosine (a potent inhibitor of platelet aggregation via stimulation of platelet A₂ receptors) during brief I/R contributes to this improved patency.

Methods and Results—To address our first objective, we compared the time required to achieve lysis with recombinant tissue plasminogen activator and patency during the first 2 hours after lysis in dogs in which 1-hour thrombotic occlusion was preceded by brief I/R (10-minute coronary occlusion/10-minute reperfusion) versus 20-minute uninterrupted perfusion (controls). Time to lysis was accelerated in the I/R group versus the control group (11±1 versus 35±6 minutes, P=0.004). In addition, the duration of subsequent reocclusion was reduced (17±12 versus 30±11 minutes), and the area of the flow-time profile (normalized to baseline flowx120 minutes) was increased (64±12% versus 35±7%, P=0.04) in the I/R cohort. The protocol was then repeated, but all dogs were pretreated with the adenosine A₂/A₁ antagonist CGS 15943 (CGS, 1.5 mg/kg). Time to lysis (38 versus 39 minutes) and subsequent patency were comparable in the CGS+control group versus the CGS+I/R group.

Conclusions—Brief antecedent I/R enhances the efficacy of coronary thrombolysis in this canine model, which is due, at least in part, to an adenosine-mediated mechanism.

Key Words: ischemia • thrombolysis • adenosine • myocardial infarction

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