CIRCULATION IN SKELETAL MUSCLE 



'379 



60 1 20 O 60 



TIME IN SECONDS 



I20 



fig. 24. Results showing that reduction of the arterial blood 

 pressure did not affect the resistance changes in the muscle 

 vessels of the calf of the leg after exercise. Solid circles: average 

 of 1 2 runs in six subjects with pressure in plethysmograph 

 raised 67 cm H ; 0. Open circles: average of 12 control runs on 

 the same subjects. A: simple scale; B: semilogarithmic scale. 

 [From Dornhorst & Whelan (68). j 



from capillaries could not have been far from zero. 

 Others have found that venous blood from exercising 

 muscles seldom contains less than 6 vol per cent 

 oxygen (12, 31), and that muscle oxygen tension 

 may be very low. For example, during tetanic 

 stimulation of the cat's soleus oxygen saturation of the 

 myoglobin falls from 90 to 50 per cent (152). Rough- 

 ton has kindly told me that this corresponds to a fall 

 in muscle oxygen tension of from about 40 to 5 mm 

 Hg (F. J. W. Roughton, personal communication). 

 Ehrlich (76) too, who measured the reduction of 

 alizarin blue, found that muscles reduce very ac- 

 tively. 



But what about the effect of really low arterial 

 blood oxygen tensions on muscle flow? The trouble 

 is that these kill the heart. It is true that Fleisch el a/. 

 (86), who perfused hind legs with blood artificially 

 ventilated with 3 per cent oxygen, did not find much 

 dilator effect. But their preparation had lost basal 

 tone and was probably widely dilated before the 

 effect of rarefied oxygen was tested. Because of the 

 damage done to the blood of the cat by pumps (91) 

 the experimenter who wishes to test the effect on 

 muscle blood flow of complete reduction of the blood 

 is faced with a very awkward technical problem. In 

 dogs Guyton ct al. (62) recorded some vasodilatation 

 in the hind legs when the oxygen tension of the blood 

 perfusing them was reduced to 30 per cent. We do 

 badly need a study of the effect on muscle blood flow 

 and gaseous metabolism of progressive reduction 

 in 2 tension of the arterial inflow right down as 



far as zero. It will be recalled that Hilton & Eicholtz 

 (124) found that ventilating the animal with N 2 

 was accompanied by a large increase in coronary 

 blood flow. Results have not yet appeared on the 

 effect of ventilating the animal with N 2 , on the hy- 

 peremia of exercise, nor on the effect on the hypere- 

 mia of exercise of reducing arterial oxygen tension 

 down to zero. 



So much for oxygen lack. It was Gaskell's (107) 

 idea that muscle blood vessels were opened by vaso- 

 dilator metabolites liberated from the skeletal muscle 

 fibers. It was he who first painted the arteries of the 

 frog's mylohyoid with 1:10,000 lactic acid and ob- 

 served the vasodilatation. However, lactic acid is 

 probably not responsible for exercise hyperemia. 

 Exercise is accompanied by the usual hyperemia in 

 muscles that have been poisoned with moniodoacetic 

 acid to prevent the formation of any lactic acid 

 (112, 162). Exercise is accompanied by hyperemia 

 in patients whose muscles, owing to congenital 

 absence of phosphorylase, are unable to form lactic 

 acid (146, 170). And there are awkward differences 

 between blood flow and lactic acid time relations 



(i33)- 



Fleisch & Sibul (85) found that neutral lactate 



had no dilator effect. That of injected lactic acid 

 they thought to be due to its pH. Other substances 

 which caused vasodilatation in concentrations of 

 Mo to *300 m l P er m ' blood were methylglyoxal, 

 Na-pyroracemic acid, acetaldehyde, acetates, sodium 

 acetoacetate, salts of fatty acids, and adenosine 

 phosphate. Their actions were additive. Fleisch & 

 Weger (88) investigated the action of fructose 

 1 ,6-diphosphate, dihydroxyacetaone phosphate, phos- 

 phoglyceric acid, phosphopyruvic acid, phospho- 

 glycerol, and creatine phosphate on the blood 

 vessels of the cat's hind leg. All were inactive or 

 weakly dilator. However, their results were not of 

 much quantitative value because they used pump 

 perfusion and worked with a preparation that had 

 lost basal tone. 



Gaskell (107) had suggested that CO 2 might be a 

 factor and while Bayliss (35) showed that it had a 

 vasodilator action Krogh (134), Fleisch (86) and 

 others have shown that its effect is too weak to be of 

 much significance. 



Fleisch & Sibul (85) thought that the additive 

 effect of carbohydrate metabolites might be con- 

 siderable because of their reduction of the pH. But 

 Gollwitzer-Meier's (112) determinations of the pH 

 changes in the venous effluent of the exercising 

 gastrocnemius of the dog did not support this hypoth- 



