Cardiac performance and creatine kinase flux during inhibition of ATP synthesis in the perfused rat heart

To study the relation among mitochondrial energy supply, cardiac performanc e, and energy transfer through creatine kinase (CK), two acute models of in hibition of ATP synthesis were compared in the isovolumic acetate-perfused rat heart. Similar impairments of mechanical performance (rate-pressure pro duct, RPP) were achieved by various stepwise decreases in O-2; supply (Po-2 down to 20% of control) or by infusing CN (0.15-0.25 mM). The forward CK f lux measured by saturation-transfer P-31 NMR spectroscopy was 6.1 +/- 0.4 m M/s in control hearts. Only after severe hypoxia (Po-2 < 40% of control) di d CK flux drop (to 1.9 +/- 0.2 mM/s at Po-2 = 25% of control) together with impaired systolic activity and a rise in end-diastolic pressure. In contra st, in mild hypoxia CK flux remained constant and similar to control(5.3 +/ - 0.5 mM/s, not significant) despite a twofold reduction in systolic activi ty. Similarly in all CN groups, constant CK flux was maintained for a three fold reduction in RPP, showing the absence of a relation between cardiac pe rformance and global NMR-measured CK flux during mild ATP synthesis inhibit ion.