Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion: A pig model of myocardial hibernation

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.