Perspectives in Biology and Medicine

RELATIONSHIP BETWEEN FLUID FLOW AND O2 DEMAND IN TISSUES IN VIVO AND IN VITRO ROLAND A. COULSON* In previous publications we presented evidence that metabolic rate was determined by the rate of blood flow [1-4]. Understandably, the theory has not met with universal acceptance, in part owing to the widespread belief that there are fundamental differences between the cells in animals with high and those with low metabolic rates. Although we did not find convincing evidence ofsignificant variations in either enzyme or substrate contents in cells of different species, we were concerned over the matter of cause and effect. Was the blood flow rapid in an animal with a high metabolic rate because his cells demanded large amounts of energy, or was energy production high because the flow rate was high? Whatever the factors responsible for differences in metabolic rates among the species, all rates are limited by blood flow. In a 70-kg man at rest, that flow is about 5 liters/minute or 71 ml/kg/min. Some ofthe blood is shunted from the arterioles to the venules, and only a fraction of the capillaries are open in a resting man at any one time; therefore, venous blood returns to the heart about 70 percent saturated with O2. On the basis of 30 percent ofthe O2 being released at the capillaries, ifthe initial arterial O2 content was 8.9 mM (20 vol%), the total used per day would be 0.3 x 8.9 x 5 x 1,440 or 19,224 mmoles or 19.2 moles/70 kg/day. This is enough to oxidize one-sixth that many moles of glucose (3.2 moles), which would weigh 576 g and produce about 2,100 kcal. If the heart is not allowed to increase the rate of blood flow, the maximum (theoretical) glucose oxidized would be limited to 3.33 x 3.2 moles if every trace of O2 in arterial blood were extracted by the tissues. The existence of arteriovenous (A-V) shunts, and so on, would reduce the The author thanks J. D. Herbert and Lewis Mokrasch, Department of Biochemistry, Louisiana State University Medical Center, for stimulating discussions of the theory, and the Louisiana Department of Wildlife and Fisheries for financial support. * Department ofBiochemistry, Louisiana State University Medical Center, New Orleans, Louisiana 70119.© 1983 by The University of Chicago. All rights reserved. 0031-5982/84/2701-0367$01.00 Perspectives in Biology and Medicine, 27, 1 ¦ Autumn 1983 | 121 actual amount extracted during maximum aerobic work to about 80 percent, permitting only about 8.5 moles of glucose to be catabolized per day. This would represent only 2.7 times the resting energy production instead of the 10-fold increase seen in a healthy man at his maximum. To produce a 10-fold increase, an increase in blood flow is mandatory. When one measures the O2 A-V difference in resting animals differing widely in metabolic rate, the values are similar. Therefore, each must have removed about the same amount of O2 from a liter of blood as it passed through the capillaries. If the A-V difference (at rest) is nearly constant, then if one animal has 10 times the metabolic rate of another, it must also have a blood flow rate 10 times as fast. Fortunately, high rates ofblood flow in animals with high metabolic rates are not associated with high blood pressures. Animals with high metabolic rates are necessarily small, and since resistance in blood vessels is proportional to length, the average blood pressure in the aorta of a mouse is close to that in the aorta of a cow [5]. In any one animal, flow rates vary in proportion to changes in tissue energy requirements. Directly or indirectly, a decrease in the ratio of ATP to ADP inside the cells will trigger responses resulting in an increased rate of delivery of oxygenated blood to the capillaries. Each species, regardless of its particular metabolic rate, balances supply with demand. Within the mammals, as the smallest has a metabolic rate at least 250 times that of the largest, its oxygen requirement is then 250 times as great. If the demand is unchanged, a...