PHYSIOLOGY OF CARDIAC MUSCLE 



223 



don of a coronary artery in the heart-luna; prepara- 

 tion caused a prompt fail in creatine phosphate but 

 no change in ATP during the i to 3 min which elapsed 

 before the onset of ventricular fibrillation. 



Chronic oxygen lack, such as occurs in anemia of 

 long standing, is occasionally a cause for congestive 

 failure. Despite the increased circulatory load in 

 anemia, uncomplicated cardiac failure is a rarity in 

 patients under 40 years of age because of the multi- 

 plicity of vascular reflexes, cited above, which act to 

 provide adequate oxygen delivery to the myocardium. 

 With the onset of coronary atherosclerosis, however, 

 these protective mechanisms are partially vitiated, 

 and electron transport may i^e reduced critically 

 because of delivery of the terminal electron acceptor. 

 On, at insufficient rates. In anemia, the cardiac output 

 tends to be elevated in order to provide additional 

 oxygen to the peripheral tissues, and this puts an 

 additional burden upon the potentially anoxemic 

 heart. When cardiac failure occurs in anemia it is 

 generally of the high output type and responds to 

 blood replacement. 



Shock 



The effect of acute hemorrhagic shock upon cardiac 

 metabolism in dogs has been studied by Edwards 

 and collaborators (64) and by Hackel & Goodale 

 (91). In this form of oligemic stagnant anoxemia, 

 cardiac output, stroke volume and work, and coro- 

 nary blood flow are inarkedly reduced. In associa- 

 tion with these hemodynamic changes, these in- 

 vestigators found reduced extraction coefficients for 

 pyruvate, lactate, and glucose, although at the high 

 arterial levels observed absolute uptake of lactate 

 and glucose were maintained. Pyruvate uptake was 

 abolished during both the oligemic and normo- 

 volemic phases of hemorrhagic shock despite elevated 

 arterial values. Cardiac work efficiency dropped 

 markedly during the oligemic phase and remained 

 depressed after reinfusion of blood. In fact, Wiggers & 

 Werle (257) and Sarnoff" and co-workers (209) noted 

 evidence of myocardial failure following the infusion 

 of blood into animals with hemorrhagic shock. In 

 regard to the precise biochemical lesion in this type 

 of anoxemia, the data are not definitive. Bing and 

 associates (64) postulated a loss of cocarboxylase from 

 the myocardium to account for the failure to metabo- 

 lize pyruvate, although no direct measurements of 

 cocarboxylase were made. The continued utilization 

 of lactate by these hearts in shock argues against a 

 serious loss of cocarboxylase, since both pyruvate 



and lactate extractions are markedly depressed in 

 thiamine deficiency in dogs (92). The marked loss of 

 work efficiency by the heart in shock suggests un- 

 coupling either of oxidative phosphorylation or of 

 the contractile mechanism. Hackel & Goodale (91) 

 have suggested that the epinephrine release ac- 

 companying hemorrhagic shock may play a key 

 role in this alteration in cardiac metabolism, since 

 hypotension due to spinal anesthesia does not cause 

 the same cardiac inefficiency. Further experimental 

 data are required before the controversy regarding 

 the biochemical lesion in the myocardium in hemor- 

 rhagic shock can be resohed. 



Beriberi 



In the ab.sence of adequate dietary thiamine, all 

 tissues undergo depletion of cocarboxylase (thiamine 

 pyrophosphate), the coenzyme required by the 

 pyruvic and a-ketoglutaric dehydrogenases, and by 

 transketolase for normal enzymatic activity. Under 

 these conditions the o.xidation of pyruvate and other 

 carbohydrate precursors of pyruvate cannot proceed 

 to completion, and blood pyruvate and lactate rise. 

 A decrease in transketolase activity is probably un- 

 important, since the pentose shunt is normally in- 

 active in cardiac muscle. In thiamine-deficient rats 

 and ducks, Olson and his colleagues (180) showed 

 that there was a relationship between the rate of 

 pyruvate disappearance in vitro and the thiamine 

 content of the heart slice. Although pyruvate utili- 

 zation did not decline until the heart muscle co- 

 carboxylase content had been reduced from a normal 

 of 10 MS per g to about 2.5 ^g per g, further reduc- 

 tion in thiamine content resulted in a precipitous 

 drop in pyruvate utilization. Hackel et al. (92) showed 

 that thiamine deficiency in dogs resulted in "dry" 

 beriberi, with no edema and no elevation of venous 

 pressure, despite a markedly altered myocardial 

 metabolism. The extraction of pyruvate and lactate 

 by the heart was markedly reduced despite high 

 arterial levels so that only 29 per cent of the energy 

 needs of the heart were met by carbohydrate. Further- 

 more, they noted that the extraction of oxygen from 

 the coronary arterial blood varied inversely with 

 coronary flow, a highly abnormal finding which 

 suggested that hydrogen transport was limited in 

 these hearts by the lack of cocarboxylase. Although 

 most thiamine deficiency in experimental animals 

 is dry, transient congestive heart failure has been 

 produced in thiamine-deficient pigeons (231). 



Both "wet" and "dry" beriberi occur in man. 



