PHYSIOLOGY OF CARDIAC MUSCLE 



215 



OH OH 



Adenosine triphosphate (ATP) 

 CHj 



I 



HN--P = 

 I 

 0" 



Creatine phosphate (CP) 



FIG. 16. Two high-energy phosphate compounds present 

 in a cardiac muscle, ATP and CP. 



muscle and cardiac muscle (6:1) is attributed by 

 Szent-Gyorgyi (233) to the different requirements of 

 skeletal and cardiac muscle. The first type can rely 

 upon reserve energy and a strongly developed glyco- 

 lytic system, whereas the second type must rely upon 

 a steadv supply of energy provided by a highly de- 

 veloped oxidati\e mechanism. The rates of formation 

 and utilization of high-energy phosphate are more 

 closely matched in cardiac than in skeletal muscle 

 (181). Dinitrophenol has been shown by Fawaz and 

 his co-workers (70) to depress the CP but not the 

 ATP concentration of heart muscle in the heart-lung 

 preparation, suggesting that CP is used to maintain 

 the ATP concentration. Ligation of a coronary artery 

 was also found to reduce the CP concentration of the 

 heart in the heart-lung preparation, although no 

 changes in ATP were noted within the i to 3 min 

 elapsing before the onset of ventricular fibrillation. 

 The administration of glucose was noted by Rebar 

 et al. (202) to increase the content of glycogen and 

 CP, no doubt by increasing ATP formation be\ond 

 the needs of the heart for ATP utilization. 



Energy Utilization 



The ATP formed in substrate oxidation is the 

 "metabolic coinage of the cell" (232). It is this cur- 

 rency that pays for all of the work of the cell. In 

 cardiac muscle most of the energy liberated is chan- 



neled into mechanical work via the contractile process. 

 The muscle fiber must also carry out a certain amount 

 of chemical work in activating substrates, synthesizing 

 structural or storage materials as glycogen, protein, 

 and lipids, and maintaining the integrity of mem- 

 branes for transport of substrate and conduction of 

 the action potential. These proces.ses will Ije con- 

 sidered briefly under the head of chemical work. 



CHEMICAL WORK. It has already become apparent 

 that a certain amount of chemical work must be per- 

 formed on most of the substrates utilized by the 

 heart in order to make their bond energv available 

 to the heart in sub.sequent reactions. This is true of 

 glucose, fatty acids, and acetoacetate but not true 

 of lactate, pyruvate, jS-hydroxybutyrate, or glutamate. 

 Two moles of ATP are required to store a mole of 

 glucose as glycogen. It is beyond the scope of this 

 presentation to consider the pathways of reactions 

 by which proteins and lipids and sterols are syn- 

 thesized (48), but the.se are all endergonic reactions 

 requiring the input of high-energy phosphate bonds. 

 The needs of cardiac muscle in this regard are not 

 excessive, since protein turnover in muscle is low 

 compared to visceral tissues and the muscle has no 

 secretory activity involving a need for continuous 

 synthesis of lipids and proteins. Dreyfus et al. (60) 

 found that skeletal myosin turnover as measured with 

 isotopic glvcine in the rat was very slow for 30 days 

 and then abruptly changed, suggesting dissolution 

 of myofibrils at periodic intervals. Rat heart slices 

 synthesize fatty acids and cholesterol from acetate- 

 i-C'^ and glucose-U-C'' slowly when compared with 

 liver or kidney (179, 182). There is no doubt, how- 

 ever, that the variety of lipids found in heart muscle 

 are synthesized in situ at slow rates. 



MECH.-XNic.AL WORK. Siucc the piouccr work of Hill 

 (loi) and Meyerhof (156), muscle physiologists have 

 sought a hypothesis that would adequately explain 

 the coupling of chemical energy to mechanical work 

 in the myofiijril. Meyerhofs view that lactic acid 

 fermentation was the direct source of energy for con- 

 traction gave way to Lundsgaard's (143) that creatine 

 phosphate was the immediate source of contractile 

 power. The refinements in knowledge of the inter- 

 mediary metabolism of carbohydrate and of the 

 formation of high-energy phosphate bonds has now- 

 led to the current view that ATP is the immediate 

 source of energy for contraction as it is for all other 

 work processes and that CP is utilized to replace 

 ATP if the steady generation of phosphate bonds is 



