Adenosine protects ischemic and reperfused myocardium by receptor-mediated mechanisms.
To evaluate the role of adenosine receptors in the mediation of adenosine-induced protection of the heart during ischemia and reperfusion, isolated rabbit hearts were perfused at constant flow with 1 microM adenosine started before low-flow ischemia followed by reperfusion. Adenosine delayed the time of onset of ischemic contracture [to 28 +/- 19 (SD) min compared with 10 +/- 10 min in control hearts] and decreased the amplitude of ischemic contracture (29 +/- 16 vs. 48 +/- 14 mmHg; P < 0.05 for each compared with controls). This protection was accompanied by an increase in tissue ATP content (1.72 +/- 0.78 vs. 0.96 +/- 0.23 mumol/g; P < 0.05) and stimulation of anaerobic glycolysis (lactate production of 0.78 +/- 0.28 mumol.g-1 x min-1 compared with 0.53 +/- 0.23 mumol.g-1 x min-1; P < 0.05). Functional recovery during reperfusion was enhanced by adenosine (developed pressure 88 +/- 16% compared with 57 +/- 23% of baseline; P < 0.05), and tissue necrosis, assessed by creatine kinase release, was decreased. The potent, nonselective adenosine receptor blocker 8-phenyltheophylline (10 microM) blocked all of the salutary effects of adenosine. Adenosine given only at reperfusion modestly attenuated reperfusion-induced contracture. The results suggest that exogenous adenosine attenuates ischemic injury by receptor-mediated stimulation of anaerobic glycolysis. During reperfusion its protective action is related to vasodilation.
Janier
M F
MF
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Vanoverschelde
J L
JL
Bergmann
S R
SR
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism; D006019:Glycolysis; D006321:Heart / Q000503:physiopathology*; D066298:In Vitro Techniques; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption; D010710:Phosphates / Q000378:metabolism; D011817:Rabbits; D011983:Receptors, Purinergic / Q000502:physiology*
D010710:Phosphates; D011983:Receptors, Purinergic; D003402:Creatine Kinase; D000241:Adenosine