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(Circulation. 1999;100:843-848.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Brief Myocardial Ischemia Attenuates Platelet Thrombosis in Remote, Damaged, and Stenotic Carotid Arteries

Presented in part at the 47th Annual Scientific Sessions of the American College of Cardiology, Atlanta, Ga, March 30, 1998, and published in abstract form (J Am Coll Cardiol. 1998;31:168A).

Katsuya Hata, MD, PhD; Peter Whittaker, PhD; Robert A. Kloner, MD, PhD; Karin Przyklenk, PhD

From the Heart Institute, Good Samaritan Hospital and Department of Medicine (Section of Cardiology), University of Southern California, Los Angeles, Calif.

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—Brief antecedent periods of coronary artery occlusion improve subsequent vessel patency in damaged and stenotic coronary arteries via release of adenosine from ischemic/reperfused myocardium and resultant adenosine receptor stimulation. However, the site of receptor stimulation—circulating blood-borne elements (ie, platelets) versus vessel-wall components of the culprit artery—remains unclear. If platelet adenosine receptors are involved, then the benefits of brief coronary occlusion (1) should be manifested systemically and improve patency at a remote site and (2) should be inhibited by an antagonist of adenosine A₂ receptors, whereas, in contrast, (3) brief vascular occlusion not associated with appreciable adenosine release should be ineffective in improving vessel patency.

Methods and Results—In Protocol 1, anesthetized rabbits received 5 minutes of transient coronary occlusion, 5 minutes of transient bilateral carotid occlusion (purported to cause negligible adenosine release from the brain), or no intervention. All rabbits then underwent injury plus stenosis of the left carotid artery, resulting in repeated cyclic variations in carotid blood flow (CFVs). Carotid patency during the initial 2 hours after stenosis (assessed by quantifying the nadir of the CFVs and area of the flow-time profile) was significantly enhanced with antecedent coronary—but not carotid—occlusion versus controls. In Protocol 2, improvement in carotid patency after brief coronary occlusion was corroborated in anesthetized dogs. However, the benefits of brief coronary occlusion were abrogated by the A₂/A₁ antagonist CGS 15943.

Conclusions—Brief antecedent coronary artery occlusion enhanced vessel patency in remote, damaged, and stenotic carotid arteries, largely due to adenosine receptor stimulation on circulating elements.

Key Words: adenosine • platelets • thrombosis • ischemia • cerebrovascular circulation

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