Time course and determinants of recovery of function after reversible ischemia in conscious dogs

Abstract

The postischemic recovery of contractile function [measured as systolic wall thickening (WT)] was analyzed in 21 conscious dogs undergoing a 15-min coronary occlusion followed by 7 days of reperfusion (REP). Average WT was still depressed 24 h after REP (85% of base line, P less than 0.001) and returned to base line by 48 h. Analysis of individual dogs, however, revealed marked variability, whereby some recovered completely by 1 h of REP and others required up to 48 h. WT recovered completely within 30 min in dogs with collateral blood flow (CBF) greater than 50% of nonischemic zone flow (NZF) but was still impaired at 24 h (P less than 0.05) in those with CBF less than 25% of NZF. There was a close, curvilinear relation between WT during the first 4 h of REP and transmural CBF, which was described best by an exponential equation WT (as percent of base line) = P0-P1e-P2.CBF(as % of NZF) (r2 = 0.92 at 1 h, 0.76 at 2 h, 0.71 at 3 h, and 0.72 at 4 h), where P0, P1, and P2 are regression coefficients. Importantly, the slope of the regression line was very steep at low CBF, implying that even small differences in CBF produce large differences in postischemic function. Heart rate, systolic pressure, and rate-pressure product during ischemia were also related to WT after REP, but when the effect of CBF was taken into account, the influence of these variables became insignificant. The size of the occluded vascular bed did not correlate with postischemic WT. The presence of hypokinesis or akinesis during ischemia was associated with rapid recovery after REP, but there was no relation between ischemic and postischemic dysfunction when dyskinesis was present during occlusion. Thus, on the average, regional function remains depressed for 24 h after a 15-min ischemic episode, but there is considerable individual variability. This variable rate of recovery is determined primarily by the severity of blood flow reduction during ischemia. Systemic hemodynamics may modulate recovery of function indirectly via their effects on ischemic blood flow.