Importance of heart rate for acute hibernation in isolated blood-perfused piglet hearts

Background. Hibernating myocardium may benefit from revascularization, Ther e are several experimental models for acute hibernation, In intact hearts l ow-now ischemia causes time-dependent metabolic alterations, termed "metabo lic adaptation". In isolated heart preparations metabolic responses to low- flow ischemia vary, and signs of metabolic adaptation are not consistently found In isolated hearts global ischemia may cause bradycardia unless the h earts are paced. We hypothesized that the lack of consistent metabolic adap tation to low-flow ischemia in isolated hearts might be due to bradycardia during ischemia. In this study we investigated the influence of heart rate on metabolism and function in an isolated heart preparation. Methods. Isolated blood-perfused piglet hearts were subjected to 120 min 10 % flow. In groups A (n=9) and B (n=4) hearts were not paced during ischemia , in groups C (n=5) and D (n=5) hearts were paced at pre-ischemic heart rat e during ischemia, Results. Without pacing, heart rate declined to approximate to1/3 during is chemia and anaerobic metabolism showed a slight decline over time. With pac ing, production of protons, pCO(2) and lactate showed a bell-shaped curve w hich peaked at 20-25 min of ischemia, followed by a subsequent decline towa rds the end of ischemia (overall p<0.001 for all), However, reperfusion rev ealed impaired recovery of function in paced hearts compared to non-paced h earts (53+/-7% vs 77+/-4%, p<0.05) concomitant with higher release of creat ine kinase (455+/-93 IU/100 g vs 106+/-13 IU/100 g, p<0.01). Conclusions. When heart rate is allowed to decline during low-flow ischemia in isolated piglet hearts, signs of metabolic adaptation are not evident. When hearts are paced during ischemia time-dependent alterations in anaerob ic metabolism occur, resembling observations seen in intact beating hearts. However, paced hearts also show indications of increased cellular injury, indicating that in paced hearts the metabolic consequences are mostly due t o increased irreversible cell injury. Thus, the model for acute hibernation with 10% flow in isolated blood-perfused piglet hearts are critically depe ndent on badycardia during ischemia.