Biochemical mechanisms of acute contractile failure in the hypoxic rat heart.
The biochemical mechanism of acute contractile failure in the hypoxic rat heart was investigated using phosphorus nuclear magnetic resonance to measure intracellular acidosis and the concentrations of phosphocreatine, adenosine triphosphate (ATP), and inorganic phosphate while cardiac mechanical function was simultaneously monitored. The cytosolic free [ADP] was calculated from the creatine kinase equilibrium expression. Mechanical activity, phosphocreatine and ATP concentrations, and intracellular pH all decreased after the onset of hypoxic perfusion. Neither a reduction in ATP concentration nor limitation in its rate of production contributed to the early contractile failure. Calculations suggest only a modest (approximately 10%) difference in cytosolic free energies of ATP hydrolysis. Neither the time course nor the extent of depression of mechanical function correlated well with intracellular acidosis. In conjunction with other observations, these results were consistent with the view that the myocardial inotropic state may be directly responsive to the ambient PO2. The overall rate of ATP turnover was assessed from measurements of oxygen utilisation and lactate production in both normoxic and hypoxic hearts. Surprisingly, despite more than an 80% reduction in mechanical activity during hypoxia, no significant decrease in the rate of ATP utilisation was noted during hypoxia. This suggests that unidentified non-contractile processes may hydrolyse ATP at relatively higher rates during hypoxia.
P M
PM
Matthews
D J
DJ
Taylor
G K
GK
Radda
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D000860:Hypoxia / Q000378:metabolism*; D007773:Lactates / Q000096:biosynthesis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007773:Lactates; D010710:Phosphates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate