22C; 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



coronory arteriovenous 

 oxygen difference {vol.%) 



6 8 10 12 U 16 18 20 22 24 26 28 



arterial oxygen level (vol.%) 



FIG. 2 1 . Myocardial oxygen extraction in relation to 

 arterial oxygen level in man. [Goodale el al. (82).] 



cell. It follows from this that the mechanisms adjust- 

 ing coronary flow (and hence oxygen delivery at a 

 given oxygen content) must be extraordinarily sensi- 

 tive to the needs of the hydrogen transport chain. 

 Only under such conditions would the cardiac muscle 

 cell "permit" the oxygen content of the arterial blood 

 (ordinarily proportional to hemoglobin concentra- 

 tion) to determine the oxygen uptake and thus keep 

 the myocardial oxygen extraction coefficient (A-V)/'A 

 constant. 



It is thus seen that the heart demonstrates broad 

 flexibility in the utilization of substrates for energy 

 production without a change in either its work per- 

 formance or work capacity. There is little evidence 

 that total lack of arterial substrate per se occurs in 

 any clinical situation to the extent that it embarrasses 

 the cardiac "capacity" for work. Metabolic dis- 

 turbances in heart muscle may be sufficiently marked 

 to cause a reduction in free energy available for con- 

 traction, as noted in the next section. 



PHYSIOLOGY OF SUBSTRATE EXTRACTION UNDER 

 PATHOLOGIC CONDITIONS 



The extraction of specific substrates by heart 

 muscle, which is variable in conditions of health, may 

 be even more variable in conditions of disease. In 

 some situations the variations may be of such a nature 

 that the total amount of oxidizable substrate ex- 

 tracted remains constant and the processes of energy 

 production are not impaired. In other situations, the 

 alterations in the intermediary metabolism of carbo- 



hydrate and/or fat may be so large as to impair elec- 

 tron transport or oxidative phosphorylation and re- 

 sult in restricted energy production and even cardiac 

 failure (185). Some of these conditions will be dis- 

 cussed in the ensuing portion. 



Hypoxia 



In acute hypoxia, the oxygen supply of the normal 

 heart is protected by a number of vascular reflexes 

 governing coronary flow and by the excellent design 

 of the myocardium for rapid diffusion. In dogs, made 

 hypoxic by breathing 7 to 10 per cent oxygen, coro- 

 nary sinus catheterization has shown that increased 

 coronary flow and more complete extraction of oxygen 

 from the coronary blood preserve myocardial oxygen 

 delivery (63). In dogs made more severely hypoxic 

 by breathing 3 to 6 per cent o.\ygen, left auricular 

 pressure may rise just prior to death (58). Death 

 under these conditions, however, usually results from 

 the greater vulnerability of the central nervous system. 

 A similar situation occurs in cyanide poisoning which 

 produces hypoxia by inactivation by cytochrome 

 oxidase. The heart is again less vulnerable than other 

 critical organs because of its high content of this en- 

 zyme. 



In coronary atherosclerosis, the cardiac reserve 

 may be lowered through reduction in the efficacy 

 of vascular adjustments to increased cardiac work 

 loads and hypoxia. Gorlin et al. (85) found that 

 coronary flow in patients with coronary artery disease 

 did not increase after nitroglycerin, whereas marked 

 vasodilatation occurred in normal subjects. In such 

 patients this investigation has also noted a decrease 

 in lactate extraction consistent with an increase in 

 aerobic glycolysis. In experimental graded coronary 

 occlusion (with plastic spheres) in dogs, Bing and 

 his colleagues (20) have shown that transient re- 

 duction (10-15 min) in the extraction rates for glu- 

 cose, lactate, and pyruvate (sometimes to negative 

 values) accompany the reduction in cardiac output, 

 coronary flow, peripheral blood pressure, and de- 

 creased myocardial oxygen consumption. Under 

 such conditions, leading to local ischemia and in- 

 farction, the patent coronary arteries appear to be 

 maximally dilated as indicated by a fall in coronary 

 vascular resistance. SarnofT (208) found that restric- 

 tion of coronary flow from a main coronary artery 

 cau.sed a depression in the ventricular function curve 

 (plot of stroke work versus filling pressure for that 

 ventricle) of the left but not the right ventricle in the 

 open-chest dog. Fawaz el al. (70) observed that liga- 



