REVERSIBILITY OF MILD TO MODERATE ISCHEMIC INJURIES IN THE ISOLATED RAT-HEART - A CHARACTERIZATION BY P-31-NMR AND BY PHYSIOLOGICAL AND ULTRASTRUCTURAL INDEXES

We have studied cardiac function, metabolism, and ultrastructure durin g reperfusion after global ischemia of short duration (6 and 12 minute s) in isolated rat hearts. Our aim was to obtain more detailed informa tion on the reversibility of changes following presumedly mild and mod erate ischemic injuries by use of multiple time-based indices. In a mo dified Langendorff perfusion system, hearts were subjected to 24 minut es of Control perfusion and 6 or 12 minutes of ischemia followed by 1. 5 or 24 minutes Of reperfusion. During the experiments we monitored le ft ventricular developed pressure (LVDP), heart rate, and coronary flo w rate, and intracellular phosphocreatine (pCr), inorganic phosphate ( P(i)), pH, and ATP by P-31 nuclear magnetic resonance spectroscopY. Th e number of cells with sarcolemmal and nuclear injuries was counted. O ur main findings during 24 minutes of reperfusion following 6 and 12 m inutes 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 r apid versus slower recovery of pH. Ultrastructural examination reveale d sarcolemmal and nuclear 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 be tween an essentially normal ultrastructure, and a depressed recovery o f LVDP, reduced ATP, and an overshoot of PCr upon 24 minutes of reperf usion after 12 minutes of ischemia. This may indicate a postischemic d ysfunction closely related to stunning.