High energy phosphates and the force of contraction of cardiac muscle

• Published in: Circulation (New York, N.Y.) N.Y.), 1961-08, Vol.24 (2), p.416-428
• Main Authors: FURCHGOTT, R F, LEE, K S
• Format: Article
• Language: English
• Subjects: Heart - physiology; Humans; Myocardium; Old Medline; Phosphates - metabolism
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.24.2.416

This paper reviews studies performed by the authors and by others on the levels of high energy phosphate compounds—adenosine triphosphate (ATP), adenosine diphosphate (ADP), and creatine phosphate (CP)—of cardiac muscle under various conditions influencing contractile force. Interference with energy metabolism decreases both contractile force and high energy phosphates, especially CP. Certain types of experimental "failure" are associated with decreases in high energy phosphates; however, other types of "failure" occur without significant decreases in these phosphates. In addition, marked decreases or increases in contractile force, independent of significant changes in high energy phosphates, can be produced by drugs, by changes in heart rate, or by alterations in extracellular concentrations of cations. A decrease in force when levels of high energy phosphate are normal may be attributed to a deficiency in the utilization of these energy stores for mechanical work. The nature of this deficiency has been analyzed in isolated cat papillary muscles by simultaneously determining the activity oxygen consumption and contractile force per beat. In the case of decreases in contractile force due either to reduced heart rate or to spontaneous heart failure, the deficiency may be attributed almost completely to a loss in efficiency in the conversion of chemical energy in the high energy phosphates to mechanical energy (work). Cardiac glycosides, in restoring contractile force, do so by restoring the efficiency of this conversion. In the case of decreases in contractile force resulting from lowered extracellular Ca ++ , the deficiency may be attributed partly to a loss of efficiency in this conversion and partly to a reduction in amount of high energy phosphate utilized per beat.