Dichotomy in the Post-ischemic Metabolic and Functional Recovery Profiles of Isolated Blood- versus Buffer-perfused Heart

Abstract

There is evidence that buffer- and blood-perfused hearts differ in their post-ischemic functional recoveries. The present study was designed to: (i) compare ischemia-induced contracture and post-ischemic functional recovery, and (ii) investigate whether the recovery profiles were related to either the release of purines and norepinephrine or high-energy phosphate content. Rat hearts ( n=8/group) were perfused at 37°C with buffer (60 mmHg) or blood (60 mmHg from a support rat), made globally ischemic (15 min) and reperfused (15 min). The onset and severity of ischemic contracture were identical in both models [left ventricular end-diastolic pressure (LVEDP) at the end of 15 min ischemia was 30±5 and 27±4 mmHg respectively; P= n.s.]. However, the rate and extent of post-ischemic left ventricular developed pressure (LVDP) differed considerably. Blood-perfused hearts exhibited an initial rapid and complete recovery of LVDP followed by a steady decline to approximately 60% of pre-ischemic values. Buffer-perfused hearts recovered to only 80% after 5 min reperfusion and remained at this level for the duration of reperfusion. LVEDP was higher in buffer-perfused than in blood-perfused hearts during the first 5 min of reperfusion; thereafter, LVEDP fell in buffer-perfused hearts to a level than was not significantly different from the observed in blood-perfused hearts. In buffer-perfused hearts, coronary flow recovered to 90% within 5 min and then remained constant; in blood-perfused hearts flow recovered to 100% by 1 min and continued to rise to a maximum by 7 min (201±15%). This increase appeared to mirror the secondary decline in LVDP. During the first 4 min of reperfusion, in both preparations, venous norepinephrine increased to six- to nine-fold of pre-ischemic values and then fell rapidly to near control levels by 6–9 min. Total purine release was high in early reperfusion in both groups. At the end of 15 min reperfusion, the tissue adenylate pool was similar in both groups. This study demonstrates that the nature of the perfusate used for an isolated rat heart preparation: (i) does not appear to influence the severity of ischemic injury as assessed by ischemic contracture, but (ii) does influence the qualitative and quantitative characteristics of the temporal profile that describes the recovery of systolic and diastolic function during the first 15 min of reperfusion; and (iii) it has no effect upon the changes seen in a number of metabolic indices that are often used for the assessment of injury and protection.