Energetic determinants of stunning and cell damage following reoxygenation of rabbit myocardium

The energetic conditions in anoxia which lead to stunning and cell damage upon reoxygenation of the myocardium are studied in isolated papillary muscles of rabbit contracting isometrically at 20 degrees C. Before anoxia and thereafter the muscles are stimulated at 0.2 Hz, while during anoxia stimulation frequency is varied. Total creatine (CrT) content is taken as a measure of cell damage. The degree of stunning is estimated from the difference in force before anoxia and at the end of the recovery period when no creatine is lost. In anoxic rabbit papillary muscles glycogen is the substrate for lactate formation. The 'ATP reserve' of the muscle can then be calculated from: 2 ATP + PCr + ADP + 3 (glycosyl units). In control muscles it equals 482.2 mumol.g-1 dw of ATP. By varying stimulus frequency (0, 0.2, 0.5, or 1 Hz) during and the length of the anoxic period (20 to 80 min), the fraction of the ATP reserve used in anoxia is varied. It is found that the degree of stunning depends on the degree of ATP reserve depletion. When the ATP reserve becomes virtually zero force recovers to only 67% of the preanoxic value. When anoxia continues after the ATP reserve is virtually zero, creatine in the muscle decreases during reoxygenation, indicating cell damage. Apparently a hierarchy of cellular ATPases exists in the myocardium when energy is short preserving cell integrity as long as possible.