Free energy change of ATP-hydrolysis: a causal factor of early hypoxic failure of the myocardium?

Abstract

During 5 to 7 min. anoxic perfusion of isolated electrically paced rat hearts with three types of perfusion media (A: 2m m Ca 2+; B: 2m m Ca 2+ + lidocaine; C: 6m m Ca 2+ + lidocaine), the following parameters were recorded and estimated: peak intraventricular pressure and force of both regular beats and beats following paired stimulation, the same mechanical parameters under Ca 2+ bolus administration, tissue content of the following metabolites: ATP, ADP, phosphocreatine (PC), creatine (Cr), and inorganic phosphate (P i). Cytosolic concentrations were calculated using CK equilibrium equation and published data of tissue compartmentation. From cytosolic concentrations the phosphorylation potential [ATP] [ADP][P i] and free energy change of ATP hydrolysis ( dG dξ ) were calculated. The course of contractile performance and changes in tissue metabolite content are consistent with those of literature. Fast breakdown of PC stores and relatively fast reduction of contractile performance are accompanied by slow and moderate decrease in ATP. The tissue contents of the respective split products increase complementarily. None of the single metabolic parameters correlates satisfactorily with contractile performance. In contrast, steep reduction of contractile performance occurs when free energy change of ATP hydrolysis (controls 60.5 kJ/mol) is between 50 and 45 kJ/mol. According to these results the low level of free energy change of ATP hydrolysis rather than ATP deficiency, at least under anoxia, can be considered to be one main causal factor of contractile failure.