Dynamics of Early Postischemic Myocardial Functional Recovery

Abstract

Background The present study was designed to explore the relation between the duration of ischemia and the rate and extent of myocardial functional recovery after reperfusion. Methods and Results Isolated rat hearts were perfused with blood from a support animal for 15 minutes (flow rate, 2.5 mL/min; perfusion pressure, 60.1±1.3 mm Hg). Control left ventricular developed pressure (LVDP) was measured, and the hearts (six per group) were subjected to 10, 20, 30, 40, 50, 60, 70, or 80 minutes of global ischemia (37°C) and 60 minutes of reperfusion. Pacing (320 beats per minute) was instituted before and after ischemia. In all groups, transient arrhythmias occurred at the onset of reperfusion, to be followed by an early phase of recovery that peaked after 2 to 3 minutes of reperfusion. The relation between the extent of this initial recovery and the duration of preceding ischemia was described by a bell-shaped curve. Thus, the maximum initial mean recovery after 10, 20, 30, 40, 50, 60, 70, or 80 minutes of ischemia was 97%, 108%, 145%, 154%, 118%, 34%, 41%, and 24%, respectively, of preischemic LVDP. Possibly indicative of reperfusion-induced injury, LVDP then declined in all groups so that after 20 minutes of reperfusion, the mean recovery was 63%, 53%, 48%, 50%, 56%, 12%, 9%, and 5%, respectively. In the 10-, 20-, 30-, and 40-minute ischemia groups, there then was a secondary increase in LVDP, possibly indicating the start of recovery from stunning. After 60 minutes of reperfusion, the mean recovery of LVDP was 82%, 65%, 59%, 54%, 47%, 9%, 7%, and 4%, respectively; this second phase of recovery was inversely proportional to the duration of ischemia. To define the early phase of recovery that had been obscured by reperfusion-induced arrhythmias, we repeated the experiments with the inclusion of a cardioplegic infusion (St Thomas’ solution for 2 minutes before ischemia). This significantly reduced the incidence of ventricular fibrillation during early reperfusion. The extent of the initial postischemic recovery of LVDP was similar to that observed without cardioplegia; however, the mean secondary recovery was greater in all groups. Again, the relation of early transient (2 to 5 minutes) recovery to the duration of ischemia was represented by a bell-shaped curve, whereas the secondary recovery was inversely related. Conclusions Although the results of the present study confirm the protective properties of cardioplegia, they also shed some light on the nature of reperfusion-induced injury and myocardial stunning and their complex relation to the severity of the preceding ischemia.