Regulation of systolic force and control of free energy of ATP-hydrolysis in hypoxic hearts

In isolated isometrically working rat hearts during graded, constant pressure hypoxic saline perfusion ( P o 2 140–700 mmHg) heart rate was changed experimentally between 80 and 400/min. The following parameters were recorded or estimated: peak systolic pressure, dP dt max , dP t min , oxygen consumption (V o 2 ), venous P o 2 , ATP, ADP, phosphocreatine, creatine and inorganic P. Free energy of ATP hydrolysis ( dG dξ ) was calculated from cytosolic concentration using CK-equilibrium equation. Two predominant responses of the hearts to hypoxia were observed, • — pronounced negative force frequence relationship • — maintained energetic state (Free energy, dG dξ ) at the respective level of hypoxia if contractile force and beating rate were varied by a factor of 4–5. The enhanced force frequency relationship with a maintained free energy level is interpreted in terms of downregulation of EC-coupling (including duration of action potential) which comprises a possible cardioprotective effect.