Impact of delayed reperfusion of myocardial hibernation on myocardial ultrastructure and function and their recoveries after reperfusion in a pig model of myocardial hibernation

This study examined the effect of delayed reperfusion of myocardial hiberna tion from 24 hours to 7 days on myocardial ultrastructural and functional c hanges and their recoveries after reperfusion. Background: We have previously shown in pigs that after reperfusion the fun ctional and structural alterations in short-term myocardial hibernation whi ch was reperfused in 24 hours can recover in 7 days. The effect of delayed reperfusion of hibernating myocardium on the extent and severity of cellula r and extracellular structural changes of hibernating myocardium, and their recoveries after reperfusion is not known. Methods and Results: A severe L AD stenosis was created in 27 pigs, reducing resting flow by 30-40% immedia tely after placement of the stenosis and producing acute ischemia as eviden ced by regional lactate production, a decrease in regional coronary venous pH, reduced regional wall thickening (from 38.5 +/- 5.1% to 10.4 +/- 8.0%) and a 33% reduction of regional oxygen consumption. The stenosis was mainta ined either for 24 hours in 9 pigs (group 1) with LAD flow of 0.65 +/- 0.13 ml/min/g (38% reduction), or for 7 days in 17 pigs (group 2) with LAD flow of 0.67 +/- 0.14 ml/min/g (36% reduction). There were no differences (p = NS) in the reduction of wall thickening, rate-pressure product, lactate pro duction, or regional oxygen consumption between group 1 and group 2. Quanti tative morphometric evaluation of the ultrastructure on electromicrographs revealed a greater decrease in sarcomere volume and a higher incidence of m yocytes with reduced sarcomere volume in 7-day than in 24-hour hibernating regions (53 +/- 19% versus 33 +/- 14%, p < 0.05). Patchy myocardial necrosi s with replacement fibrosis was common, but 6 of the 18 pigs had no myocard ial necrosis or replacement fibrosis in the 7-day hibernating group, and 4 of 9 pigs had no patchy myocyte necrosis in the 24 hour hibernating group. In 6 pigs in group 1 in which the stenosis was then released and hibernatin g myocardium reperfused in 24 hours, regional wall thickening recovered to 30 +/- 6% (p = NS compared to baseline) after one week of reperfusion. Tn 1 2 pigs in group 2 in which the stenosis was released and hibernating myocar dium reperfused in 7 days, regional wall thickening recovered slowly, from 10.1 +/- 7.2% to 18.1 +/- 8.3% at one week (n = 5) and to 28.0 +/- 3.6% at 3-4 weeks of reperfusion (n = 7, p < 0.05 compared to baseline). Similarly, the sarcomere volume or myofilament recovered significantly (p < 0.01) and was not different compared to the normal region (p = NS) in the 24-hour hi bernating region of group 1, but the recovery was much slower and was incom plete at 4 weeks (p < 0.01) compared to baseline in the 7-day hibernating r egion of group 2. Recovery of regional wall thickening correlated with ultr structural recovery (p < 0.01). By multivariate stepwise regression analysi s, the degree of LAD flow reduction, the extent of fibrosis, and myofilamen t loss were independent predictors of the extent of functional recovery. Co nclusions: In a porcine model of myocardial hibernation with myocardial hyp operfusion, systolic dysfunction, and metabolic adaptations, a longer perio d of myocardial hibernation with delayed reperfusion was associated with mo re severe abnormalities of myocytes. an increasing interstitial fibrosis, a nd more protracted myofibrillar and functional recoveries after reperfusion . The extent of functional recovery is related to the degree of coronary fl ow reduction, the severity of the ultrastructural changes, and the extent o f interstitial fibrosis. (C) 2000 by Elsevier Science Inc.