Inhibition of the @entity908 kinase reaction decreases the contractile reserve of isolated XXXX hearts.

@entity1734 @entity908 @entity141 @entity8867 @entity1920 @entity519 @entity35 @entity857 @entity1063 @entity11064
To define the relation between @entity11064 transfer via @entity908 kinase (CK) and the ability of the intact beating heart to do work, we chemically inhibited CK activity and then measured cardiac performance under physiological and acute stress conditions. Isolated perfused @entity35 hearts were exposed to @entity8867 (IA) and subjected to one of three cardiac stresses: hypercalcemic ( @entity141 = 3 mM) buffer perfusion (n = 7), @entity1063 (2 mumol/min) infusion (n = 6), or @entity519 buffer perfusion (n = 5). IA decreased CK activity to near zero, measured in intact hearts by 31P magnetization transfer, and to 2% of control CK activity, measured in myocardial homogenates. The CK isoenzyme profile was unchanged, suggesting nonselective IA inhibition of all isoenzymes. Mitochondria isolated from IA-treated hearts had normal @entity857 :O ratios, state 3 respiratory rates, and unchanged acceptor and respiratory control ratios. Neither actomyosin adenosinetriphosphatase nor @entity1920 kinase activities were changed. After IA exposure, end-diastolic pressure, left ventricular developed pressure, and heart rate were unchanged for at least 30 min at physiological perfusion pressures, but large changes were observed during stress conditions. The increase in left ventricular developed pressure induced by hypercalcemic perfusion and by @entity1063 infusion decreased by 39 and 54%, respectively. During @entity519 , the rate of @entity1734 depletion was decreased by 57%, left ventricular developed pressure declined, and end-diastolic pressure increased faster than in controls. These results show that inhibition of CK to < 2% of control activity by IA reduced contractile reserve by approximately 50%. We conclude that CK activity is essential for the expression of the full dynamic range of myocardial performance.
