Mechanism of early "pump" failure of the ischemic heart: possible role of adenosine triphosphate depletion and inorganic phosphate accumulation.
A marked reduction in oxygen tension and adenosine triphosphate (ATP) content accompanies the early "pump" failure of the ischemic heart. However, it appears to be unlikely that decreased ATP supplies for energy-consuming reactions in the myocardial cell cause the observed decrease in myocardial contractility because of the high ATP-affinity of the substrate-binding sites of known energy-consuming reactions in the heart. Furthermore, lack of chemical energy for the contractile proteins and known ion pumps would tend to promote rigor and not a decrease in contractility. Recent evidence suggests that ATP at concentrations greater than those needed to saturate the substrate-binding sites of energy-consuming reactions can exert modulatory effects on ion fluxes. These modulatory effects of ATP could allow a less severe decrease in ATP concentration to inhibit both calcium entry into the myocardial cell and calcium efflux from the sarcoplasmic reticulum. In addition, the large amounts of phosphate liberated from phosphocreatine and ATP could, by causing formation of insoluble calcium-phosphate precipitates, trap calcium in the sarcoplasmic reticulum and mitochondria in the ischemic myocardium. These proposed explanations for the early "pump" failure in the ischemic heart, together with other theories such as intracell acidosis, appear to warrant further study.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism
D010710:Phosphates; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate