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 pig s. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate how reduction m aintained for 24 hours and whether any such structural alterations are reversible after reperfusion. Methods and Results A severe left anter ior descending coronary artery (LAD) stenosis was created with a reduc tion of resting flow to approximate 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 ch anges 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 steno sis 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 myoc ardial ischemia, as evidenced by reduced regional wall thickening (fro m 37.2+/-6.9% at baseline to 11.5+/-6.8%), regional lactate production (-0.34+/-0.28 mu mol . g(-1). min(-1)), and a decrease in regional co ronary venous pH (from 7.41+/-0.035 at baseline to 7.30+/-0.030). At 2 4 hours, the reductions in coronary flow and wall thickening were main tained relatively constant and the rate-pressure product was relativel y unchanged, but lactate production ceased and regional H+ concentrati on 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 min utes 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 necros is 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 ele ctron 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 p igs, and the ultrastructural changes reverted to normal. Conclusions I n this pig model, moderately ischemic myocardium undergoes metabolic a nd structural adaptations but preserves the capacity to recover both f unctionally and ultrastructurally after reperfusion.