Myocardial performance and free energy of ATP-hydrolysis in isolated rat hearts during graded hypoxia, reoxygenation and high Ke+-perfusion.

The effects of graded hypoxia, graded reoxygenation after anoxic perfusion and of different extracellular K+-concentrations on cardiac energy metabolism and performance were studied in isolated, perfused, electrically paced rat hearts. Graded hypoxia was induced by different oxygen partial pressure (PO2: 736 to 43 mmHg, nine intermediate steps; O2 supply: (AVD*CF): 300 to 21 microliters/g*min) in perfusate for 3 min, thus leading to different levels of relative mechanical steady state. Evaluated free energy change of ATP-hydrolysis (dG/d zeta) decreased largely in parallel with peak systolic pressure (Psyst) and systolic dP/dtmax, whereas diastolic dP/dtmin declined already to lowest values with moderate hypoxia. For regular beats and beats potentiated by paired stimulation the same relationships were found. Complete reoxygenation of hearts perfused anoxically beforehand (10 or 30 min, PO2 less than 6 mmHg), restored Psyst and dG/d zeta completely. Graded reoxygenation from different levels of hypoxia resulted in restitution of dG/d zeta and Psyst to the same levels as in graded hypoxia. The inotropic effect of paired stimulation was moderately reduced. Cytosolic Pi-levels remained increased during partial reoxygenation and exhibited no distinct relationship with mechanical performance. High extracellular K+ (13.5 mM) resulted in increased Psyst and elevated dG/d zeta-levels. Cardiac failure during graded hypoxia and high K+ occurred at comparatively high dG/d zeta levels. Reoxygenation with high K+, led to recovery of dG/d zeta levels but not of Psyst values. According to the results obtained in early hypoxic failure free energy dependence of Na+/K+-ATPase is of minor relevance whereas free energy dependence of sarcoplasmic Ca2+ regulating processes appears to be important.