226 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



work at a mecfianical disadvantage for a period of 

 time. The time required for tiie induction of failure 

 is generally inversely related to the seriousness of the 

 mechanical disadvantage. Cardiac failure of this 

 type may result from congenital anomalies of the 

 valves and great vessels, valvular disease, or hyper- 

 tension. It may also occur at "normal loads" in 

 atrophic or infarcted cardiac muscle. 



In these conditions, the energy production of 

 the heart is normal and the fjiochemical reactions 

 occurring in the cytoplasm and sarcosomes proceed 

 effectively. That failure can occur in the presence 

 of normal oxidative metaf:)olism has been demon- 

 strated in the heart-lung preparation (98, 224, 245), 

 the open-chest dog (210), the intact dog (181), and 

 in the human subject with hypertension or valvular 

 disease (22, 25, 83). By means of cardiac 

 catheterization, these latter workers (25, 83) found 

 no decrease in coronary blood flow, oxygen extrac- 

 tion, or substrate utilization in patients with ad- 

 vanced congestive heart failure with roentgenologic 

 evidence of left ventricular enlargement. Since cardiac 

 output in these patients was reduced, it was calcu- 

 lated, even assuming normal heart size, that the 

 efficiency of the heart was low. The inability of these 

 investigators to show any defect in myocardial oxygen 

 consumption in failure does not support the older 

 view of many pathologists, summarized Ijy Harrison 

 (94), that hypoxia within the hypertrophied cardiac 

 muscle fiber is responsible for the failure of con- 

 tractility. Further, the study of the level of ATP and 

 CP in the myocardium of the failing heart-lung 

 preparation by Wollenberger (258) demonstrated 

 no depletion of these sources of free energy for con- 

 traction. 



In studies of the pathologic physiology of this 

 type of congestive heart failure, Olson ( 1 74) has 

 studied the metabolic behavior of the failing heart 



in dogs subjected to cardiac valvular surgery. Chronic 

 low output congestive heart failure characterized by 

 edema, ascites, weakness, reduced exercise tolerance, 

 cardiomegaly and hepatomegaly, with ultimate eleva- 

 tion of end diastolic filling pressures in Ijoth the right 

 and left ventricles, was produced in dogs by avulsion 

 of the tricuspid valve and stenosis of the pulmonary 

 artery (12). Although initially right-sided, heart 

 failure induced in this way eventually becomes 

 generalized as indicated fjy depressed ventricular 

 function curves in both ventricles (12) and a positive 

 inotropic response to digitalis in both chambers 

 (184). 



The cardiac metabolism of a series of dogs in 

 congestive heart failure due to valvular disease was 

 compared with a series of healthy control animals. 

 C^ardiac catheterization with intuljation of the pul- 

 monary artery and the coronary sinus was performed 

 on each animal. \'alues for resting cardiac output, 

 coronary blood flow, total carbohydrate and NEFA 

 uptake, and cardiac oxygen consumption for normal 

 dogs and for dogs with congestive heart failure second- 

 ary to tricuspid insufficiency and pulmonary stenosis 

 (TI/PS) are presented in table 2. It may be seen 

 that although the cardiac output is decreased in 

 congestive heart failure associated with valvular 

 disease, coronary blood flow, and myocardial oxygen 

 usage were unchanged from normal. The extractions 

 of glucose, lactate, and pyruvate were slightly in- 

 creased in the dogs with congestive heart failure 

 so that the total contribution of carbohydrate to 

 energy production was increased and the contribution 

 of fatty acids reduced in the failing heart. The de- 

 tailed protocols are presented elsewhere. The re- 

 sults of the phosphate fractionation in ventricular 

 muscle from normal animals and those in failure are 

 shown in table 3. No differences between groups were 

 noted for any of the fractions studied. The fact that 



T.-VBLE 2 . Cardiac Performance and Metabolism in Normal Dogs and Dogs With 

 Congestive Heart Failure Due to Valvular Disease 



CBH — Carbohydrate. f Tricuspid insufficiency and pulmonary stenosis. 



