Effects of experimental congestive heart failure, ouabain, and asphyxia on the high-energy phosphate and creatine content of the guinea pig heart.

Abstract

The left ventricles of guinea pigs have been assayed for adenosine triphosphate, adenosine diphosphate, adenylic acid, phosphorylcreatine, free creatine, and inorganic phosphate. These determinations have been made under various experimental conditions which affect the performance of the heart in vivo, such as experimental congestive heart failure, acute asphyxia, and the influence of the cardiac glycoside, ouabain. In 20 guinea pigs with experimental congestive heart failure, sacrificed 1 to 18 days after surgically producing a coarctation of the ascending aorta, a significant fall in PC (54 per cent), ATP (24 per cent), and total creatine (34 per cent) was observed. The extent of the loss of high-energy phosphate compounds and total creatine paralleled the severity of cardiac failure as determined by abnormal intraventricular pressure pulses, ventricular hypertrophy, and gross and microscopic pathology. In animals with experimental congestive heart failure, the cardiac glycoside ouabain produced significant slowing of the heart, a positive inotropic effect, and a lowering of abnormally high right ventricular systolic and left ventricular diastolic pressures. At the height of the response to ouabain, there was a further fall in PC to 25 per cent of normal without any change in ATP concentration. The positive inotropic action of ouabain is, therefore, not due to an ability of the drug to increase high-energy phosphate levels in failing heart muscle. Acute asphyxia produces a very rapid fall in the PC concentration (85 per cent lost in two minutes) and a much slower fall in ATP (33 per cent lost in eight minutes). Recovery of normal mechanical activity, after a period of asphyxia, by rebreathing occurs with little, if any, restoration of ATP and at a time when the PC concentration is only about 25 per cent of normal. These experiments indicate that steady-state levels of high-energy phosphate compounds are not as important in determining the mechanical capacity of the heart as are their rates of synthesis.