The role of intracellular [Ca2+] and [H+] in contractile failure of the hypoxic heart.
When oxidative metabolism is inhibited in heart muscle, developed tension often increases slightly before decreasing below control. We have examined the possible mechanisms underlying these changes in developed tension in two series of experiments. In the first series of experiments, the photoprotein aequorin was used to monitor intracellular free [Ca2+] [( Ca2+]i) in papillary muscles during inhibition of oxidative phosphorylation, using either cyanide or hypoxia. The observed changes of developed tension were independent of changes in [Ca2+]i. It was therefore possible that these changes of tension were due to changes of intracellular pH (pHi). We tested this idea in a second series of experiments, using 31P nuclear magnetic resonance to monitor pHi, [ATP], and phosphocreatine concentration [( PCr]) in Langendorff-perfused ferret hearts. During the application of cyanide, pHi increased transiently before decreasing to below control. [PCr] decreased throughout this period, but [ATP] did not change. It is concluded that the observed changes of pHi could account for most of the observed changes of developed tension. It is suggested that the initial increase of pHi is due to PCr breakdown and the subsequent decrease of pHi to accelerated anaerobic glycolysis.
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003327:Coronary Disease / Q000503:physiopathology*; D005289:Ferrets; D006352:Heart Ventricles / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000503:physiopathology; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D012966:Sodium Cyanide / Q000494:pharmacology
D010710:Phosphates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D012966:Sodium Cyanide; D002118:Calcium