MECHANICAL AND METABOLIC FUNCTIONS IN PIG HEARTS AFTER 4 DAYS OF CHRONIC CORONARY STENOSIS

Objectives. This study sought to evaluate the functional and metabolic consequences of imposing a chronic external coronary stenosis around the left anterior descending coronary artery for 4 days in an intact p ig model. Background. A clinical condition termed hibernating myocardi um has been described wherein as a result of chronic sustained or inte rmittent coronary hypoperfusion, heart muscle minimizes energy demands by decreasing mechanical function and thus avoids cell death, The use of chronic animal models to simulate this disorder may assist in esta blishing causative associations among determinants to explain this phe nomenon. Methods. A hydraulic cuff occluder was placed around the left anterior descending coronary artery in eight pigs, Coronary flaw velo city was reduced by a mean (+/-SE) of 49 +/- 5% of prestenotic values, as estimated by a Doppler velocity probe, After 4 days the pigs were prepared with extracorporeal coronary circulation and evaluated at flo w conditions dictated by the cuff occluder, Substrate utilizations wer e described using equilibrium labeling with [U-C-14]palmitate and [5-H -3]glucose. Results were compared with a combined group of 21 acute an d chronic (4 day) sham animals. Results. Four days of partial coronary stenosis significantly decreased regional systolic shortening by 54%. Myocardial oxygen consumption was maintained at aerobic levels, and r est coronary flows were normal, Fatty acid oxidation was decreased by 43% below composite sham values, and exogenous glucose utilization was increased severalfold, Alterations in myocardial metabolism were acco mpanied by a decline in tissue content of adenosine triphosphate. Conc lusions. These data suggest that chronic coronary stenosis in the abse nce of macroscarring imparts an impairment in mechanical function, whe reas coronary flow and myocardial oxygen consumption are preserved at rest. The increases in glycolytic flux of exogenous glucose are simila r to observations on glucose uptake assessed by fluorine-18 2-deoxy-2- fluoro-D-glucose in patients with advanced coronary artery disease, We speculate that intermittent episodes of ischemia and reperfusion are the cause of this phenomenon.