AJP - Heart and Circulatory Physiology, Vol 253, Issue 2 412-H421, Copyright © 1987 by American Physiological Society
Temporal relation between energy metabolism and myocardial function during ischemia and reperfusion
K. Clarke, A. J. O'Connor and R. J. Willis
The purpose of the present investigation was to study the relation between
energy metabolism and contractile function in the isovolumic guinea pig
heart. 31P nuclear magnetic resonance spectroscopy was used to measure
changes in the intracellular levels of creatine phosphate, ATP, inorganic
phosphate, and pH during 2.43 min total global ischemia and 2.43 min
reperfusion, with a time resolution of 9.7 s. From these data, cytosolic
changes in the phosphorylation potential, [ATP]-to-[ADP] ratio, free-energy
change of ATP hydrolysis, and concentration of free ADP were estimated. The
simultaneous monitoring of functional and biochemical parameters allowed
them to be directly correlated with respect to time and with respect to
each other. No significant changes in ATP were detected at any time, but
changes in all other biochemical data were highly correlated with changes
in contractile function. Kinetic analysis, using a nonlinear least-squares
fit of the experimental points, revealed that the changes in most
parameters fitted monoexponential functions. Each parameter was ranked
according to its half time, which revealed that the phosphorylation
potential was the only metabolic parameter to change at a rate faster than
loss of contractile function during ischemia, and all metabolic changes,
with the exception of pH, led the recovery of contractile function during
reperfusion, the most rapid change occurring in the free ADP concentration.
It is concluded that the cytosolic phosphorylation potential controls the
contractile function of the heart and that cytosolic free ADP is important
in the control of mitochondrial oxidative phosphorylation.
