Adenosine protects ischemic and reperfused myocardium by receptor-mediated mechanisms
Janier, M.F.; Vanoverschelde, J.L.; Bergmann, S.R.
American Journal of Physiology 264(1 Pt 2): H163-H170
1993
ISSN/ISBN: 0002-9513 PMID: 8430842 Document Number: 422139
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 mu-M 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 mm Hg; P lt 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 mu-mol/g; P lt 0.05) and stimulation of anaerobic glycolysis (lactate production of 0.78 +- 0.28 mu-mol cntdot g-1 cntdot min-1 compared with 0.53 +- 0.23 mu-mol cntdot g-1 cntdot min-1; P lt 0.05). Functional recovery during reperfusion was enhanced by adenosine (developed pressure 88 +- 16% compared with 57 +- 23% of baseline; P lt 0.05), and tissue necrosis, assessed by creatine kinase release, was decreased. The potent, nonselective adenosine receptor blocker 8-phenyltheophylline (10 mu-M) 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.