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HANDBOOK OF PHYSIOLOGY -^ CIRCULATION I 



formation of an actomyosin with normal contractile 

 properties (178). Benson (14) found that the acto- 

 myosin content of ventricle from animals in con- 

 gestive heart failure (TI/PS) was reduced below 

 normal and had certain abnormal properties, namely, 

 decreased viscosity per unit of actomyosin and a 

 decreased change in viscosity per unit of actomyosin 

 upon the addition of ATP. More recently, Benson 

 and co-workers (15) have found that the in vitro 

 contractilitv of glycerol-extracted muscle strips 

 from both the right and left ventricles of dogs with 

 heart failure due to TI/PS was markedly reduced 

 and that a depressed ventricular function curve 

 similar to that observed in vivo could be constructed 

 from the data. Since glycerol-extracted muscle 

 retains little else than the basic contractile system 

 and responds to ATP like isolated actomyosin, it 

 seems reasonable to assume that the defective con- 

 tractility observed by Benson and co-workers (15) 

 must be due to an altered actomyosin fibril. Kako & 

 Bing (115) have noted a similar decrease in the 

 contractility of actomyosin bands prepared from 

 failing human heart muscle post mortem when com- 

 pared with control preparations. It seems reasonable 

 to conclude that the biochemical lesion in congestive 

 heart failure of the low-output type is located in the 

 contractile mechanism itself, presumably because of 

 an alteration in myosin, and hence actomyosin. 

 The stimulus for this change may be the chronic 

 stretch to which heart muscle working at a mechanical 

 disadvantage is subjected. The extensive hydrogen 

 bonding of myosin may well be disrupted under 

 such conditions and permit aggregation to occur 



(65). 



Much additional research is required to elucidate 



the molecular events underlying the heart beat in 

 health and disease. The conception of heart failure 

 as a manifestation of specific biochemical lesions in 

 the myocardium, however, should lead to new in- 

 vestigations which will define with greater precision 

 than is now possible the molecular pathogenesis of 

 the various forms of the disease. It must also be 

 remembered that although many extracardiac 

 factors may modify the degree of manifest clinical 

 failure in the organism, in the final analysis, the heart 

 fails when its generation of free energy or its utiliza- 

 tion of that energy in the process of contraction is 

 insufficient for the circulatory load imposed. 



The author would like to acknowledge the helpful sugges- 

 tions of Doctor Clyde M. Williams and the clerical assistance 

 of Miss Anna D. Francis in the preparation of this manuscript. 



APPENDIX 



Enzyme Differences in Heart and 

 Skeletal Muscle 



