Relationships between pre-ischemic ATP and glycogen content and post-ischemic recovery of rat heart

The effect of depletion of energy stores of rat hearts on their resistance to a total of 25 min ischemia was investigated by using a 31P-NMR method. Three experimental groups were compared: (1) pyruvate-perfused hearts depleted of adenine nucleotides (35% of normal) by 2-deoxyglucose (DG) treatment and containing deoxyglucose-6-phosphate (c. 40 mumol/g dry wt); (2) hearts partially depleted of glycogen stores (40 to 50% of initial) by long-term (2h) perfusion with pyruvate; (3) glucose perfused (11 nM) hearts with normal ATP and glycogen contents. By the end of ischemia the intracellular pH was decreased by 0.33, 0.90 and 1.40 units, respectively. Time to peak of ischemic contracture increased in this series from 3 to 18 and 24 min, respectively. At the peak of ischemic contracture ATP content was c. 30 to 40% (6 to 8 mumol/g dry wt) of normal value in all three groups. Reperfusion of hearts resulted in development of significant reperfusion contracture in glucose-perfused hearts and minor contracture in other series. Recovery of high energy phosphates and cardiac work index in DG-treated, glycogen-depleted and glucose-perfused hearts were: for phosphocreatine (PCr), 72, 102 and 83%; for ATP, 29, 47 and 56% and for cardiac work, 66, 78 and 24%, respectively. Recovery of cardiac work did not correlate linearly with tissue ATP. These data demonstrate that post-ischemic recovery of the contractile function of isovolumic heart may be dissociated from pre-ischemic myocardial ATP and glycogen contents. This dissociation can be explained by the two major factors: (1) the contribution of ischemic acidosis and catabolites accumulation to the cell damage and (2) by ATP compartmentation.