220 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



for a relaxed myosin. These authors point out that 

 relaxing factors such as EDTA, myokinase, and ATP- 

 creatine phosphorylase either bind magnesium or 

 elevate ATP levels. Both of these act to decrease 

 ATPase activity and promote relaxation (36). This 

 view postulating deformation of myosin is contra- 

 dicted most directly by the observation that the A 

 bands of muscle, which contain myosin, do not ap- 

 preciably shorten under most physiological conditions. 



StrauJD & Feuer (229) have suggested that the 

 polymerization of G-actin to F-actin is a crucial 

 reaction in muscular contraction. This idea, not 

 popular in the last decade, may deserve re-examina- 

 tion in the light of the Huxley model with its assign- 

 ment of a more important role to the actin filaments. 

 The early hypothesis of Astbury (7) that contraction 

 resulted from a phase change in myosin has not been 

 confirmed experimentally. Bailey el al. (g) have sug- 

 gested that the function of tropomyosin may be to 

 control the rate of operation of the contractile cycle 

 by interacting with actin. In skeletal and cardiac 

 muscles in which the buildup and decay of tension 

 are rapid, actin is relatively more abundant than 

 tropomyosin. On the other hand, in those smooth 

 muscles, in which buildup and decay of tension are 

 slow, tropomyosin is a much more prominent con- 

 stituent. 



The observation of Fleckenstein et al. (72) and 

 Mommaerts (161) that no observable ATP or CP 

 breaks down during a single contraction is disillusion- 

 ing, although .some other labile phosphate compound 

 may be replenishing the ATP split in a single twitch. 

 Chance & Williams (41) have also shown that the 

 rise in ADP following stimulation of frog sartorius 

 muscle was low, i.e., only 0.008 /zmole per gram per 

 twitch. This represents only about i per cent of the 

 calculated ATP breakdown for one twitch. 



It seems likely, howes'er, that ATP is the ultimate 

 source of energy in muscular contraction as in other 

 types of cellular work. The efficiency in the conversion 

 of ATP to mechanical work in cardiac muscle varies 

 widely from about 20 to 60 per cent, indicating that 

 the "coupling" of ATP utilization to actomyosin 

 function is consideral)ly looser than the coupling of 

 hydrogen transport to ATP formation (113). Under 

 normal conditions the over-all efficiency of the heart 

 thus varies from 12 to 36 per cent. 



PHYSIOLOGY OF SUBSTRATE UTILIZATION 



Tiie intact beating heart may extract and utilize 

 a variety of substrates from the coronary blood. Much 



o 

 o 



UJ 



Z 



60 90 120 



ARTERIAL LEVEL MG% 



150 



FIG. 20. Extraction of glucose, lactate, and pyruvate by 

 muscle in vivo. These lines represent averages of large numbers 

 of determinations upon man and dog and demonstrate the 

 uptake of substrate at various concentrations. 



evidence is available from studies of cardiac muscle 

 homogenates and slices (33, 68, 158, 180), of heart- 

 lung preparations (31, 139, 153, 205), isolated per- 

 fused hearts (122), and intact hearts in man and 

 clog approached via coronary sinus catheterization 

 (81-83), "^'^st pyruvate, lactate, glucose, acetate, 

 acetoacetate, /i-hydroxybutyrate, amino acids, and 

 fatty acids may serve as sources of energy for heart 

 muscle. 



Under physiologic conditions glucose, lactate, 

 pyruvate, and fatty acids (as NEFA), and to a lesser 

 extent, acetate, ketone bodies, and amino acids are 

 the main fuels of the heart. The extent to which each 

 substrate contributes to the energy requirement of 

 the heart in vi\o is influenced by its concentration 

 in arterial l)lood as well as by the state of nutrition 

 and endocrine balance of the organism. Furthermore, 

 in the intact heart tliere appears to be a definite 

 threshold of extraction for some substrates. Although 

 these are very close to zero for pyruvate (0.6 =h 0.2 

 mg %) and lactate (2.5 ± 0.5 mg %), the threshold 

 for glucose extraction is considerably higher (59 ± 6 

 mg 'O- Since this threshold behaxior (shown in 

 fig. 20) is lost in cardiac muscle slices, it is probably 

 a function of an intact cellular membrane. This is 

 further supported by the effects of diabetes and in- 



