Functional and metabolic evidence of enhanced myocardial tolerance to ischemia and reperfusion with adenosine.
An isolated, isovolumetrically contracting rat heart preparation, perfused at constant flow, was used to test the hypothesis that adenosine treatment (100 microM) throughout the experiment could enhance the repletion of adenosine triphosphate and the recovery of ventricular function following 10 minutes of global, normothermic (37 degrees C) ischemia. Left ventricular developed pressure was measured with an intraventricular balloon, and myocardial adenine nucleotides were measured from freeze-clamped tissues in a parallel series of experiments. The adenosine triphosphate level in the adenosine-treated hearts was not different from that of the untreated control hearts at the end of 30 minutes of equilibration but was significantly (p less than 0.05) higher at the end of 10 minutes of ischemia and at 15, 30, and 60 minutes of reperfusion. Left ventricular developed pressure in the adenosine-treated group at the end of 30 minutes of equilibration (92 +/- 3 mm Hg) was not significantly different from that of the control hearts (101 +/- 10 mm Hg). During the reperfusion period the control group returned to 75% +/- 7%, 73% +/- 6%, and 73% +/- 6% of the preischemic control function at 15, 30, and 60 minutes of reperfusion, respectively. The adenosine-treated group had significantly greater return of function to 86% +/- 3%, 96% +/- 3%, and 95% +/- 3% of the preischemic control at 15, 30, and 60 minutes of reperfusion, respectively. In a protocol to assess the effect of adenosine during ischemia, we found that adenosine (100 microM) increased the time to onset of ischemic contracture by 50% from 12 +/- 3 to 18 +/- 3 minutes and decreased the rate of net adenosine triphosphate degradation. Our data suggest that under these experimental conditions, adenosine enhances myocardial preservation by reducing the net degradation of adenosine triphosphate during ischemia and facilitating the repletion of adenosine triphosphate during reperfusion.
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000032:analysis; D010477:Perfusion; D051381:Rats
D000255:Adenosine Triphosphate; D000241:Adenosine