PHYSIOLOGY OF CARDIAC MUSCLE 225 



them large amounts of U.S. P. thyroid powder. 

 Values for cardiac output, coronary blood flow, and 

 myocardial oxygen usage were augmented in dogs 

 from 50 to 100 per cent. Determinations of the 

 levels of total acid-soluble phosphate, inorganic phos- 

 phate, adenosine triphosphate, and creatine phosphate 

 in the ventricles of these dogs and rats showed no 

 decrease below normal. These results suggested that 

 in the steady state, at augmented work loads, the 

 processes of energy liberation and energy utilization 

 were so balanced as to maintain the usual concentra- 

 tion of high-energy phosphate compounds in ven- 

 tricular tissue. Further, studies of in vitro oxidative 

 phosphorylation of heart ventricle from hyperthyroid 

 rats and dogs have been carried out ijy the atraumatic 

 polarographic method of Chance & Williams (40). 

 High P/O values during a-ketoglutarate oxidation 

 were obtained for both normal and hyperthyroid 

 heart muscle, in good agreement with the studies of 

 normal tissue by others (186). In view of these data, 

 the mechanism of the cardiac failure in thyrotoxicosis 

 remains obscure. It seems unlikely that the effects of 

 hyperthyroidism are purely hemodynamic. Crispell 

 et al. (51) found that protein anabolism as measured 

 with N'^-glycine was depressed in hyperthyroidism. 

 It may be that anabolic reactions leading to protein 

 synthesis, and hence to the maintenance of the con- 

 tractile proteins of the heart, may be affected in 

 thyrotoxicosis and influence contractility of the heart. 

 Further work is required before this enigma can be 

 solved. 



PATHOLOGIC .ALTERATION IN CONTRACTILE PROTEINS 



Since current views of the mechanism of contraction 

 in cardiac muscle stress the importance of the spatial 

 and functional relationships in the contractile cycle 

 of the filaments of the myofibril, it follows that dis- 

 turbances in the ultrastructure of the heart caused by 

 primary disease of the muscle or alteration in the 

 configuration of the contractile proteins may lead to 

 cardiac dysfunction and failure. The evidence is 

 mounting that most of the common types of cardiac 

 failure are due to defects in energy utilization (18, 

 185), i.e., a failure of the myofibril to assimilate 

 phosphate bond energy or to shorten properly in 

 the contractile cycle. Although the biochemical 

 lesions have not been determined with certainty in 

 these disorders, it is considered important in the over- 

 all consideration of the physiology of cardiac muscle 

 to mention the work which has been done to in- 



augurate biochemical study of this important area 

 and to encourage additional work. 



Primary Disease of Cardiac Muscle 



The study of biochemical disturbances in primary 

 diseases of cardiac muscle in man and animals has 

 scarcely begun. No significant electron microscopic 

 studies of the ultrastructure of the myocardium have 

 been carried out in cases of myocarditis due to rheu- 

 matic fever, diphtheria, or bacterial or virus infec- 

 tions. One can only speculate from the microscopic 

 findings that disorganization of the ultrastructure of 

 the myofibril may incapacitate the contractile fila- 

 ments. The processes of fatty degeneration and 

 hyaline segmentation of the myocardium in extreme 

 situations of dilatation and necrosis as a result of 

 inflammation, circulatory occlusion, or chemical 

 agents may interfere at several points in the normally 

 orderly processes of energy production and utiliza- 

 tion, and thereby induce cardiac failure. Glycogen 

 disease, which has been mentioned briefly, results in 

 crowding of the sarcoplasm with glvcogen granules 

 which are isiochemically inert, and which ultimately 

 embarrass the contractile mechanism by competition 

 for space. The same may be said of neoplastic events 

 in cardiac muscle. 



Although the muscular dystrophies primarily in- 

 volve skeletal muscle, there is evidence (16, 75, 211) 

 that the dystrophic process also affects the heart 

 and may result in congestive heart failure (75). 

 Although study of the cardiac contractile proteins 

 has not been carried out in muscle dystrophy of any 

 kind, studies of the contractile proteins from dystrophic 

 skeletal muscle from vitamin E-deficient rabbits 

 have been made. Aloisi (5) has reported that marked 

 changes occur in the amount and kind of myosin 

 present in skeletal muscle during the induction of 

 vitamin E-deficiency in the rabbit. The birefringence 

 of the A band is lost and the quantity of myosin which 

 can be isolated chemically is drastically reduced. 

 Furthermore, it appears that the viscosity and solu- 

 bility of the myosin are reduced so that the change 

 associated with dystrophy is both quantitative and 

 qualitative. One may infer that related changes may 

 be occurring in heart muscle in this condition. 



Secondary Disease of Cardiac Muscle 



Congestive heart failure of the low output type 

 generally occurs in subjects with previously normal 

 cardiac muscle, whose hearts have been obliged to 



