Increased concentrations of intracellular H+, Na+, and Ca2+ have been observed during
ischemia, and these ionic alterations have been correlated with several indexes of cell injury in a number of studies. Recently,
adenosine was proposed to play a role in ischemic preconditioning, since
adenosine antagonists block the protective effects of these brief intermittent periods of
ischemia and reflow. In this study we evaluated the protective effects of
adenosine (20 microM) on high-energy
phosphate metabolism, H+ and Ca2+ accumulation, and glycolytic rate during 30 min of no-flow
ischemia.
Adenosine was observed to slow the onset of
contracture (7.0 +/- 0.9 min) and to improve left ventricular developed pressure (62 +/- 7% of initial) during reperfusion compared with untreated hearts (5.0 +/- 0.6 min and 18 +/- 5%, respectively). Intracellular Ca accumulation at the end of 30 min of
ischemia was higher in the untreated (2,835 +/- 465 nM) than in the
adenosine-treated (2,064 +/- 533 nM) hearts, while intracellular pH fell more in the untreated (5.85 +/- 0.17) than in the
adenosine-treated hearts (6.27 +/- 0.16). Glycolytic rate and the rate of
ATP decline were significantly attenuated in the
adenosine-treated hearts during
ischemia. Thus
adenosine treatment slowed the rate of metabolism and delayed the accumulation of H+ and Ca2+ during
ischemia, resulting in better recovery of function upon reflow.