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Aged Rat Myocardium Exhibits Normal Adenosine Receptor-Mediated Bradycardia and Coronary Vasodilation But Increased Adenosine Agonist-Mediated Cardioprotection

Department of Surgery, Division of Cardiothoracic Surgery, University of Kentucky College of Medicine, Lexington.

Address correspondence to Robert D. Lasley, PhD, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536-0298. E-mail: rlasley{at}uky.edu

The purpose of this study was to determine whether aged myocardium exhibits decreased responsiveness to adenosine A₁ and A_2a receptor activation. Studies were conducted in adult (4–6 months) and aged (24–26 months) Fischer 344 x Brown Norway hybrid (F344 x BN) rats. Effects of the adenosine A₁/A_2a agonist AMP579 were measured in isolated hearts and in rats submitted to in vivo regional myocardial ischemia. Aged isolated hearts exhibited lower spontaneous heart rates and higher coronary resistance, as well as normal A₁- and A_2a-mediated responses. There was no difference in control infarct size between adult and aged rats; however, AMP579 treatment resulted in a 50% greater infarct size reduction in aged rats (18 ± 4% of risk area) compared to adult rats (37 ± 3%). These findings suggest that adenosine A₁ and A_2a receptor-mediated effects are not diminished in normal aged myocardium, and that aged hearts exhibit increased adenosine agonist-induced infarct reduction.