Functional and Structural Alterations With 24-Hour Myocardial Hibernation and Recovery After Reperfusion

Abstract

Background Short-term myocardial hibernation of 3 hours resulting from a moderate resting coronary flow reduction has been reproduced in pigs. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate flow reduction maintained for 24 hours and whether any such structural alterations are reversible after reperfusion. Methods and Results A severe left anterior descending coronary artery (LAD) stenosis was created with a reduction of resting flow to ≈60% of baseline and maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall thickening was determined by echocardiography, and local metabolic changes were measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow was reduced from 0.91±0.11 to 0.52±0.13 mL·min − 1 ·g − 1 , a 43% mean decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56±0.11 mL·min − 1 ·g − 1 at 24 hours. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening (from 37.2±6.9% at baseline to 11.5±6.8%), regional lactate production (−0.34±0.28 μmol·g − 1 ·min − 1 ), and a decrease in regional coronary venous pH (from 7.41±0.035 at baseline to 7.30±0.030). At 24 hours, the reductions in coronary flow and wall thickening were maintained relatively constant and the rate-pressure product was relatively unchanged, but lactate production ceased and regional H + concentration normalized, with a tendency toward a further reduction in regional oxygen consumption, from 3.10±0.90 mL·min − 1 ·100 g − 1 at 15 minutes after stenosis to 2.52±0.95 mL·min − 1 ·100 g − 1 at 24 hours ( P =.06), indicating metabolic adaptation of the hypoperfused regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis involving 4%, 5%, and 6% of the area at risk; and 2 other pigs had a few scattered myocytes with necrosis, detected only by light and electron microscopy. Ultrastructural changes consisted of a partial loss of myofibrils and an increase in mitochondria and glycogen deposition. Regional wall thickening recovered 1 week after reperfusion in most pigs, and the ultrastructural changes reverted to normal. Conclusions In this pig model, moderately ischemic myocardium undergoes metabolic and structural adaptations but preserves the capacity to recover both functionally and ultrastructurally after reperfusion.