Adenosine's effect on myocardial functional recovery: substrate or signal?
During induced ischemia for cardiac surgery, nucleotides are degraded while being used to maintain myocyte integrity. The resulting nucleosides washout upon reperfusion, limiting nucleotide resynthesis resulting in poor postischemic cardiac function. We studied if the mechanism of the beneficial effect of adenosine, a nucleotide precursor, which is known to improve postischemic functional recovery is as a substrate for nucleotide resynthesis or by stimulation of adenosine A1 or A2 receptors. Isolated, retrograde-perfused rabbit hearts received cardioplegia as controls or cardioplegia containing 80 microM [R]-N6-[1-methyl-2-phenylethyl]-adenosine, an A1 receptor agonist, or 200 microM 5'-(N-ethylcarboxamido)adenosine, or 200 microM adenosine alone. To assess functional recovery developed pressure, max dP/dt, pressure-rate product, coronary flow, and myocardial oxygen consumption were compared after 120 min of 34 degrees C global cardioplegic ischemia. Following ischemia and reperfusion, adenosine alone had better developed pressure, dP/dt, and pressure-rate product, while heart rates, wet weights, %H2O, end-diastolic volumes/pressures, and oxygen extraction were not significantly different between groups. While adenosine receptor stimulation may play a role, in this model the beneficial effect of adenosine on functional recovery appears to be mediated more by adenosine's role as a substrate for nucleotide resynthesis.
Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor 48109.
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D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D006339:Heart Rate; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D010101:Oxygen Consumption; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012039:Regional Blood Flow; D015398:Signal Transduction; D013379:Substrate Specificity; D014665:Vasodilator Agents / Q000494:pharmacology
D002314:Cardioplegic Solutions; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D000241:Adenosine