PHYSIOLOGY OF CARDIAC MUSCLE 



227 



TABLE 3. Partition of Acid-Soliihle Plwsplmrus in Heart 

 Muscle From Normal Dogs and Dogs in Congestive 

 Heart Failure Due to Valvular Disease 



Values for above are ± standard errors of the mean. 

 * TASP — total acid-soluble phosphorus; P; — true inorganic 

 phosphorus; CP — creatine phosphate; ATP — adenosine- 

 triphosphate. 



ventricular ATP and CP le\els do not cliange in 

 failure due to valvular disease, in agreement with 

 findings in the failing heart-lung preparations (258), 

 suggests that availaljility of high-energy fjonds for 

 myocardial contraction are not limiting in this 

 syndrome. Brody et al. (34) compared the ability of 

 ventricular muscle from failing and nonfailing heart- 

 lung preparations to carry on oxidative phosphoryla- 

 tion from pyruvate in vitro and found no difference 

 in the P:0 ratios. Similarly, no differences have 

 been found in in vitro oxidative phosphorylation of 

 heart muscle from intact normal dogs and those in 

 failure in our laboratory (192). The weight of the 

 evidence to date is that there is no biochemical defect 

 in the reactions leading to energy liberation and 

 conservation in the heart with low-output failure. 

 The study of the contractile proteins in experi- 

 mental heart failure has yielded some very interesting 

 findings. Myosin isolated from the ventricular muscle 

 of normal animals and from those with congestive 

 heart failure by the procedure of Szent-Gyorgyi 

 (234), rigorously purified by repeated dilutions and 

 preparative ultracentrifugations to remove any 

 residual actomyosin, was subjected to numerous 

 physical-chemical measurements including sedi- 

 mentation (free and approach to equilibrium), 

 diffusion (free and boundary spreading in tiie ultra- 

 centrifuge), viscosity, and light-scattering measure- 

 ments. All the myosin preparations from normal 

 animals appeared homogeneous by ultracentrifuga- 

 tion (fig. 22) and electrophoresis. Some of the data 

 are summarized in table 4. It may be seen that 

 although the Sjo.w intercept of the curve describing 

 dependence of sedimentation rate upon concentration 

 were nearlv identical for mvosin isolated from normal 



hearts (myosin C) and that isolated from failing 

 hearts (myosin F), the slope of the dependence upon 

 concentration (dS/dc) was markedly different for 

 the two preparations. In three of the preparations of 

 myosin F, a second faster moving peak appeared in 

 dilute solution with an Soo.w of about 9.5. Further, 

 the intrinsic viscosities of the two myosins were 

 markedly different. In contrast, the ATPase ac- 

 tivities of the two preparations were not significantly 

 different. The diflfusion constant (D2o,w) for cardiac 

 myosin A was 2.45 X lO"' cm- sec"' and for cardiac 

 myosin F was 0.77 X io~^ cm- sec~'. These constants, 

 together with the light-scattering behavior, led to 

 estimations of molecular weights of 223,000 for 

 myosin C (as indicated presiously) and 685,000 for 

 myosin F (226). The faster moving peak in some of 

 the myosin F preparations behaved like a polymer of 

 myosin F. 



These data are consistent with the view that an 

 abnormal stable aggregate of myosin C is formed in 

 cardiac failure and that this myosin F prexents the 



FIG. 22. Homogenous cardiac myosin from a normal dog 

 as determined by ultracentrifugation. Conditions: protein 

 concentration 0.44' (, rotor speed 56,100 rpm. T/20.6, pH 6.8, 

 ■%, » 4-77. [From Olson (177).] 



TABLE 4. Properties oj Cardiac Myosin From Xormal Dogs 

 and Dogs in Congestive Heart Failure 



Sedimentation studies carried out on dialyzed prepara- 

 tions of myosin in 0.6 M KCl at pH 6.8 in a model E Spinco 

 ultracentrifuge at 56,100 ± 7 r.p.m. at 4°C. Viscosity meas- 

 urements were made in an Ostwald viscometer at i °C. 

 ATPase measurements were made in a glycine buffer of 

 pH 9.2 at 25 °C. over a 5-ininute period. 



* -|- S.E. of mean. 



