Myocardial hibernation in the ischemic neonatal heart.

We explored the effects of sustained low-flow ischemia on function and metabolism in isolated neonatal hearts. The hearts were extracted from 21 piglets (1-12 days old) and set up as modified Langendorff preparations beating isometrically. They were perfused with red blood cell-enhanced buffer at controlled rates of coronary flow. Mechanical measurements, O2 usage, and substrate oxidation were determined simultaneously at 30-minute intervals for 2 hours. In control hearts, coronary flow was maintained at 1.8 ml/min/g. There was no significant change in mechanical function, diastolic compliance, or O2 or substrate metabolism after 2 hours. In the ischemia group, coronary flow was reduced to 0.2 ml/min/g and sustained for 2 hours. With the onset of ischemia, mechanical function promptly fell to 20% of control. Although O2 delivery was reduced to 11%, O2 extraction doubled so that myocardial O2 consumption was 22% of control, matching mechanical function. Glucose oxidation fell from 37 to 12 nmol/min/g, and lactate release appeared. These measures and ventricular compliance remained constant for the full 2 hours. Concentrations of glycogen and creatine phosphate did not differ from the control group; ATP was 76% of controls. These studies indicate that when myocardial O2 supply is limited, mechanical function rapidly diminishes, largely preserving critical energy stores and preventing irreversible myocellular injury. Although the signal remains to be determined, the strategy is similar to that employed by hibernating species to survive extended periods of O2 deprivation.