Characterization of metabolic responses to low-flow ischemia in intact pig hearts and isolated blood-perfused neonatal pig hearts.

Abstract

There are different well established experimental models of low-flow ischemia. We examined metabolic variables during reduced coronary blood flow (CBF) in intact pig hearts and isolated neonatal pig hearts, producing similar degrees of postischemic dysfunction without infarction. The isolated hearts were perfused with red blood cell enriched buffer. In eight open-chest pigs mid-LAD flow was reduced to 70% for 60 min, followed by 120 min reperfusion. Myocardial segment lengths were recorded and regional coronary venous blood was sampled. In isolated piglet hearts CBF was reduced to 50% (n = 4), 25% (n = 4), and 10% (n = 17). Only when flow was reduced to 10% did hearts show signs of anaerobic metabolism. Mechanical function was recorded by a balloon in the left ventricle and coronary venous blood was sampled. Intact pig hearts showed release of protons, CO2, and lactate which peaked after 5-10 min of ischemia and thereafter stabilized at reduced levels. In contrast, in isolated neonatal hearts exposed to 10% CBF releases of protons, CO2, and lactate were stable during ischemia with no adaptational changes over time. In a separate group (n = 4), repetitive biopsies revealed no adaptational changes over time for adenosine triphosphate and creatine phosphate during 10% CBF. Contractile function was stably reduced during ischemia in both models. During reduced CBF "metabolic adaptation" occurs in intact pig hearts. In contrast, this feature is not present in isolated blood-perfused piglet hearts. The mechanisms responsible for these differences are uncertain. However, differences in metabolism between adult and neonatal hearts and different loading conditions during ischemia might contribute.