ACADESINE IMPROVES TOLERANCE TO ISCHEMIC-INJURY IN RAT CARDIAC MYOCYTES

The ability of acadesine to modulate injury in a myocyte model of simulated ischemia was studied. When freshly isolated adult rat ventricular myocytes were subjected to 10 min of simulated ischemia and reperfusion, greater that 75% of myocytes developed hypercontracture and the amplitude of contraction of the remaining, potentially viable myocytes was markedly depressed. When cells were pretreated with 50 mu M acadesine for 5 min and exposed to acadesine during simulated ischemia and during 2-10 min of reperfusion, followed by reperfusion with control buffer, up to 90% of myocytes maintained normal morphology and could be stimulated to contract. Acadesine alone had no significant effect on amplitude of contraction of the myocytes. Acadesine is known to alter adenosine metabolism and to increase coronary sinus [adenosine] in the ischemic heart. When cells were treated with the non-selective adenosine receptor antagonist 8-sulfonylphenyltheophylline, the protective effect of acadesine was abolished. Thus, in this adult rat cardiac myocyte model of simulated ischemia, acadesine protects partially against ischemia/reperfusion injury. The protective effect of acadesine is mediated, at least in part, by an adenosine receptor-dependent mechanism.