Temporal relation between energy metabolism and myocardial function during ischemia and reperfusion

Abstract

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.

Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo.

“…Although the relationship between myocardial high-energy phosphates and function has been investigated in perfused hearts (18)(19)(20)(21) and after total coronary occlusion in vivo (1,2), there are only limited data concerning this relationship during partial reductions in regional myocardial blood flow (22,23). We have previously demonstrated that changes in high-energy phosphates, especially the PCr/Pi ratio, correlate closely with changes in myocardial blood flow under conditions of steadystate regional ischemia (24).…”

Dynamic relation between myocardial contractility and energy metabolism during and following brief coronary occlusion in the pig.

“…[4][5][6][7] However, the most rapid and pronounced changes in myocardial contractile function and energy metabolism occur during the first 30 seconds of ischemia and during the initial period of recovery after a brief ischemic interval. [8][9][10][11][12][13] Elucidating the dynamic relation between such large and rapid changes in cardiac contractile function and energy metabolism may help define the mechanisms by which cardiac contractility is regulated during and following ischemia.…”

Cardiac contractile dysfunction during mild coronary flow reductions is due to an altered calcium-pressure relationship in rat hearts.

“…Some studies suggest that vascular collapse may be an important mediator of contractile depression after acute no-flow ischemia (29,30). However, other studies have demonstrated a close relationship between the initial fall of pressure and energy phosphate metabolites after acute noflow ischemia, suggesting that vascular collapse is not important in mediating contractile depression (31,32).…”