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 (PO2 140-700 mmHg) heart rate was changed experimentally between 80 and 400/min. The following parameters were recorded or estimated: peak systolic pressure, dP/dtmax, dP/tmin, oxygen consumption (VO2), venous PO2, ATP, ADP, phosphocreatine, creatine and inorganic P. Free energy of ATP hydrolysis (dG/d xi) was calculated from cytosolic concentration using CK-equilibrium equation. Two predominant responses of the hearts to hypoxia were observed, pronounced negative force frequency relationship; maintained energetic state (Free energy, dG/d xi) 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.