Chronic dipyridamole therapy produces sustained protection against cardiac ischemia-reperfusion injury

• Published in: American journal of physiology. Heart and circulatory physiology 1999-11, Vol.277 (5), p.H2091-H2097
• Main Authors: Figueredo, Vincent M, Diamond, Ivan, Zhou, Hui-Zhong, Camacho, S. Albert
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1999.277.5.h2091

1  Cardiology Division, Lovelace Medical Center and the Department of Medicine (Cardiology) University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87108; and Departments of 2  Medicine (Cardiology), 3  Neurology, 4  Cellular and Molecular Pharmacology, and the 5  Ernest Gallo Clinic and Research Center, San Francisco General Hospital, University of California, San Francisco, California 94110 Sustained protection against ischemia-reperfusion injury is not available for patients at risk for myocardial infarction who may require emergent reperfusion therapy. Whereas ischemic preconditioning and adenosinergic agents reduce myocardial injury, they are only effective when given immediately before ischemia or reperfusion. We recently found chronic ethanol exposure, an adenosine uptake inhibitor, produced sustained cardioprotection against ischemia-reperfusion injury. We now ask whether chronic dipyridamole therapy, a clinically usable nucleoside transport inhibitor, induces similar cardioprotection. Perfused hearts from guinea pigs, given dipyridamole (4 mg · kg 1 · day 1 ) in their water for 2-6 wk ( n  = 10 for each group), underwent ischemia-reperfusion. Injury was assessed by recovery of left ventricular developed (LVDP) and end-diastolic (LVEDP) pressures and creatine kinase release. During reperfusion, hearts from dipyridamole-treated animals (6 wk) had 74% higher LVDP, 28% lower LVEDP, and 61% lower creatine kinase release versus controls. Adenosine A 1 -receptor antagonism (8-cyclopentyl-1,3-dipropylxanthine; 200 nM) abolished the protection of dipyridamole but A 2 antagonism (3,7-dimethyl-1-propargylxanthine; 10 mM) did not. Dipyridamole therapy produces sustained protection against ischemia-reperfusion injury in guinea pigs. This cardioprotection requires adenosine A 1 receptor signaling at the time of ischemia. guinea pig; heart; adenosine