Functional compartmentation of ATP and creatine phosphate in heart muscle

The relationship between ATP and creatine phosphate (CP) in heart muscle was studied in two experimental models: (a) in the intact area of the infarcted heart at various levels of energy rich phosphates; and (b) in acutely ischemic heart muscle. Myocardial ischemia and infarction was produced in dogs by ligation of coronary arteries. Biopsy samples were analyzed for ATP, ADP, CP, lactate and pyruvate at various intervals after coronary artery ligations. The relationship between the tissue content of ATP and CP in acutely ischemic muscle differs markedly from that in non-infarcted muscle. In ischemic muscle there is a positive correlation between the rate of CP breakdown () and the rate of lactate accumulation () during the first 30 sec of ischemia, whereas the rate of ATP depletion diminishes with the increase in the rate of lactate accumulation. The rates of glycolysis and high energy phosphate breakdown decrease markedly 30 sec after coronary artery occlusion. The ischemic muscle stops contracting at a relatively high ATP level of 4.5 μmole/g, when only about 20% of the ATP has been utilized, whereas the non-ischemic muscle survives and maintains contraction at ATP levels as low as 1.5 to 2.0 μmole/g. The rapid increase in anaerobic glycolysis coincides with an early inhibition of utilization of ATP stores without an interference with the utilization of CP stores. The kinetic heterogeneity of the ATP and CP depletion suggests an inhibition of transfer of intra-mitochondrial high energy phosphate to the extra-mitochondrial compartment. The early cessation of contractile activity in ischemic myocardial cells appears to be the result of a reduction in the rate of regeneration of a small pool of extra-mitochondrial ATP available for muscle contraction and other ATP requiring processes such as ion transport.