Energy metabolism in preconditioned and control myocardium: Effect of total ischemia

Myocardium which has been preconditioned by one or several brief episodes of ischemia has much slower energy utilization during a subsequent sustained episode of ischemia. Since preconditioned tissue also is 'stunned', the reduced energy utilization of preconditioned tissue may be due to reduced contractile effort. This study was done to assess whether differences in energy utilization persisted or disappeared under conditions of total ischemia, in vitro, when contractile activity was abolished in both control and preconditioned regions by hyperkalemic cardiac arrest. Preconditioned myocardium was produced in open-chest anesthetized dogs by exposing the circumflex bed to four 5-min episodes of ischemia each followed by 5 min of arterial reperfusion. Non-preconditioned anterior descending bed was used as control myocardium. Hearts were arrested with hyperkalemia after the last reperfusion period in order to reduce or eliminate the effects of contractile activity. Metabolite content was measured in sequential biopsies of the tissue. Large differences in the rate of energy metabolism of the two regions were noted during the first 15 minutes of ischemia. During this time, the preconditioned tissue utilized less glycogen, and produced less lactate, glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), and alpha-glycerol phosphate (alpha GP), than did control myocardium. Moreover, there was a much smaller decrease in net tissue ATP in the preconditioned than in the control tissue. Thus, the decrease in the demand of preconditioned tissue for energy, which has been observed in vivo, persisted despite the elimination of differences in contractile effort between control and preconditioned myocardium. Although the cause of this decrease in energy demand in preconditioned myocardium remains unknown, the present results suggest that it is not due to concomitant stunning.