Metabolism of the isolated perfused rabbit heart. I. Responses to anoxia and reoxygenation. II. Energy stores.

Cardiac performance, substrate utilization, and creatine kinase (CK) release were studied in Langendorff rabbit hearts during aerobic perfusion, 25 min of anoxia, and 75 min of reoxygenation. In study I (n = 40), increasing glucose availability during aerobic perfusion enhanced substrate utilization without influencing cardiac performance, and this effect was not modified by insulin. Reoxygenation with glucose decreased CK (milliunits per millilitre) in the coronary sinus effluent but the best early recovery occurred in hearts protected with the 'cocktail' (see Table 1) during anoxia and perfused with glucose and insulin during recovery. This early recovery of performance was associated with transient higher CK loss, an effect that may have been related to one or more of the following factors: squeezing out of interstitial CK, heterogeneous anoxic injury to the myocardium, severe sarcolemmal damage, and preferential energy utilization by the contractile apparatus. In study II (N = 82), increasing recovery of cardiac performance was associated with increasing rate of CK loss (milliunits per minute) during reoxygenation. At 15 min of recovery, creatine phosphate (CP) and ATP stores were 400 and 50% of the aerobic group suggesting the presence of a defect in energy transfer from CP to the cytosolic ADP:ATP system. Thereafter, CP levels gradually declined while ATP reached a peak concentration of 85% of the aerobic group at 30 min. By the end of recovery, ATP stores were low at 23% of control, at a time when cardiac performance and the rate of CK loss were maximal. The significance of these depleted ATP stores remains to be elucidated.