Reversibility of mild to moderate ischemic injuries in the isolated rat heart. A characterization by 31P-NMR and by physiological and ultrastructural indices.

We have studied cardiac function, metabolism, and ultrastructure during reperfusion after global ischemia of short duration (6 and 12 minutes) in isolated rat hearts. Our aim was to obtain more detailed information on the reversibility of changes following presumedly mild and moderate ischemic injuries by use of multiple time-based indices. In a modified Langendorff perfusion system, hearts were subjected to 24 minutes of control perfusion and 6 or 12 minutes of ischemia followed by 1.5 or 24 minutes of reperfusion. During the experiments we monitored left ventricular developed pressure (LVDP), heart rate, and coronary flow rate, and intracellular phosphocreatine (PCr), inorganic phosphate (P(i)), pH, and ATP by 31P nuclear magnetic resonance spectroscopy. The number of cells with sarcolemmal and nuclear injuries was counted. Our main findings during 24 minutes of reperfusion following 6 and 12 minutes of ischemia were 80% versus 53% recovery of LVDP at the end of reperfusion, an increased PCr, 80% versus 65% recovery of ATP, and a rapid versus slower recovery of pH. Ultrastructural examination revealed sarcolemmal and unclear abnormalities at the end of ischemia, these alterations being fully (rapidly versus more slowly) reversible during reperfusion. According to these findings, there was a dissociation between an essentially normal ultrastructure, and a depressed recovery of LVDP, reduced ATP, and an overshoot of PCr upon 24 minutes of reperfusion after 12 minutes of ischemia. This may indicate a postischemic dysfunction closely related to stunning.