Effect of hypothermia on changes in high-energy phosphate production and utilization in total ischemia

Abstract

The effect of temperature on the rate of production, utilization and destruction of high-energy phosphate in total ischemia was investigated in the dog heart. These studies were performed utilizing a new model of ischemic injury which was designed to test the effect of interventions on the metabolism and structure of ischemic myocardium. In this model, the normal heart was isolated from the circulation in vivo and was arrested immediately with hyperkalemic, oxygenated, autogenous arterial blood prior to the induction of total ischemia. Left ventricular pressure changes in the isolated heart were used to time the onset of ATP depletion to the levels associated with the development of contracture-rigor. Decrements in temperature progressively slowed both ATP production from anaerobic glycolysis and ATP utilization and delayed but did not prevent ATP depletion and the onset of contracture-rigor. Reserve supplies of high-energy phosphates were utilized and much of the adenine nucleotide pool was destroyed at all temperatures studied. Anaerobic glycolysis provided more than 80% of the high-energy phosphates utilized by the ischemic cell at all temperatures but always ceased when ATP levels decreased to 1–2% of control. The results demonstrate that the protective effect of hypothermia in total ischemia is due to a proportional slowing in rates of energy production and utilization. Consequently, hypothermia only delays the depletion of the high-energy phosphate reserves of the myocyte and the destruction of the adenine nucleotide pool.