The cardioprotective effects of ischemic 'preconditioning' are not mediated by adenosine receptors in rat hearts.

Abstract

Adenosine receptor activation has been proposed to explain the cardioprotective effect of ischemic preconditioning in rabbit hearts. We tested this hypothesis in a rat model by assessing whether administration of an adenosine antagonist could block the protective effect of preconditioning and whether adenosine is able to reduce infarct size in rat hearts when given before sustained coronary occlusion. We assessed the effects of the adenosine antagonist 8-(p-sulfophenyl)theophylline (SPT) and adenosine on myocardial infarct size and the incidence of ventricular arrhythmias in five groups of rats: control (nonpreconditioned)+vehicle, control+SPT, preconditioned+vehicle, preconditioned+SPT, and control (nonpreconditioned)+adenosine. All rats underwent 90 minutes of coronary artery occlusion followed by 4 hours of reperfusion while preconditioned rats underwent three 3-minute episodes of ischemia, each separated by 5 minutes of reperfusion before sustained occlusion. The area at risk was determined by intravascular injection of blue dye during coronary artery occlusion, and infarct size was determined by incubation of heart slices in triphenyltetrazolium chloride. In the nonpreconditioned control rats receiving vehicle, myocardial infarct size expressed as a percentage of the area at risk averaged 55.2 +/- 4.8%. Pretreatment with SPT and adenosine had no effect on infarct size (52.2 +/- 3.1% and 52.6 +/- 3.8%, respectively) in the nonpreconditioned control animals compared with the control animals that received vehicle. Both the preconditioned+vehicle (16.4 +/- 4.3%) and the preconditioned+SPT (18.3 +/- 5.2%) groups had a significant reduction in infarct size (p < 0.01 versus control+vehicle, control+SPT, and control+adenosine), with no difference in infarct size between the two preconditioned groups. The incidence of ventricular tachycardia was significantly decreased in both the preconditioned+vehicle (10%, p < 0.05) and the preconditioned+SPT (25.0%, p < 0.05) groups when compared with the control+vehicle (100%), control+SPT (100%), and control+adenosine groups (100%). There was, however, no significant difference in the incidence of ventricular tachycardia between the preconditioned+vehicle and the preconditioned+SPT groups. Because the adenosine antagonist SPT failed to abolish the cardioprotective effects of preconditioning and intravenous adenosine was unable to protect the hearts, it is unlikely that the mechanism of preconditioning is mediated by adenosine receptors in the rat model.