CIRCULATION IN SKELETAL MUSCLE 



■37' 



that the "after-dilatation" seen after the larger infu- 

 sions (fig. 1 -]B) might well be due to the action of 

 some carbohydrate metabolite diffusing slowly from 

 the skeletal muscle cells. This substance was perhaps 

 lactic acid as Lundholm (144) had suggested. 



Celander (55) also recorded the changes in venous 

 outflow during intravenous adrenaline infusions. 

 Arterial pressure in the cat's legs was kept constant by 

 adjusting a screw clip on the lower abdominal 

 aorta. The general picture was the same — initial 

 transient vasodilatation followed by smaller sus- 

 tained vasodilatation or by constriction according 

 to the infusion rate. There was one important dif- 

 ference. Far greater amounts of adrenaline — about 

 five times as much — had to enter the leg before the 

 sustained vasodilatation gave place to constriction. 

 In the case of intravenous infusions the local con- 

 strictor action of adrenaline was believed to have 

 been opposed by the vasodilator action of a substance 

 liberated into the general circulation. Celander 

 thought this substance was perhaps lactic acid from 

 the other muscles. 



Celander's (55) investigation also included the 

 changes in venous outflow caused by unilateral 

 splanchnic nerve stimulation. Here, too, arterial 

 pressure in the leg was kept from rising by tightening 

 a screw clip placed proximally. Stimulation at 

 frequencies of 1 to 6 per sec (corresponding to bi- 

 lateral splanchnic stimulation at 0.5-3/sec) caused 

 sustained vasodilatation in the skeletal muscles. 

 Further increase in the frequency was accompanied 

 by progressively less vasodilatation. The results may- 

 have been complicated by liberation of substances 

 from the liver; but they are interesting because it is 

 via the splanchnic nerves that the suprarenal gland 

 receives its natural stimulus. 



The human experiments on the biphasic and other 

 actions of adrenaline on muscle vessels are of par- 

 ticular interest. To quote Lewis (138), "It is perhaps 

 impossible to measure the relevant quantities so 

 precisely in man as in animals that are reduced by 

 anaesthesia to perfect stillness and control. The 

 disadvantage is offset, however, in other directions. 

 It is the reaction in man himself of which we par- 

 ticularly require knowledge. Moreover, in human 

 experiments the nutrient fluids bathing the limb are 

 those natural to the limb and to the reaction, and 

 this has not always been the case in animal experi- 

 ments. Our observations are undertaken upon the 

 unanaesthetised subject, the body as a whole is 

 healthy and undisturbed, the general circulation is 

 perfect, conditions rarely, if ever, realised in animal 



experiment, and yet probably essential to an eluci- 

 dation of the full truth where such a delicate reaction 

 is concerned." 



The subject is given a continuous infusion of saline 

 into the brachial or femoral artery throughout the 

 experiment. When appropriate the syringe contain- 

 ing the saline is replaced by another containing the 

 same saline solution to which adrenaline has been 

 added. The subject does not know whether syringes 

 contain adrenaline or not. Thus when adrenaline 

 is given, changes in forearm or calf blood flow can 

 safely be attributed to the adrenaline itself; neither 

 the saline nor emotional stress can be responsible 

 (29). Soon after the beginning of an intra-arterial 

 adrenaline infusion blood flow in the muscular part 

 of the limb increases abruptly, reaching a peak in 

 about 1 min. From the peak the flow subsides abruptly 

 to a little above the initial level at which it remains 

 for the rest of the infusion period. The vessels, as 

 it were, "yawn" — they open wide and close. This 

 initial transient vasodilatation occurs at the begin- 

 ning of infusions at rates varying from about 0.00 1 

 to 2.0 Mg per min. The biphasic pattern of the re- 

 sponse is very striking (177). When the rate of the 

 infusion is increased stepwise, each increase in rate 

 is accompanied by its own transient initial vaso- 

 dilatation (29). Intra-arterial infusion of very large 

 amounts of adrenaline, far above the physiological 

 range, causes sustained vasoconstriction. 



As figure 18 shows, the initial biphasic transient 

 dilatation is also the first response of the muscle 

 vessels of man to infusions of adrenaline given by the 

 intravenous route. The subsequent residual sus- 

 tained vasodilatation is larger than that recorded 

 during intra-arterial infusions (29,74, J 77)- Thus 

 in the forearm an intravenous infusion at 10 jug per 

 min is accompanied by an initial fivefold increase 

 in flow after which the rate subsides to about double 

 the initial value for the remainder of the infusion 

 period (5,29, 178). That both the initial transient 

 and the subsequent smaller sustained vasodilatation 

 take place in the skeletal muscle has been shown by 

 records taken with a Hensel needle implanted in the 

 calf muscles (14, 26). This is seen in figure 19. 



There is then a close resemblance between the 

 action of adrenaline on the vessels of the skeletal 

 muscle of man and of animals. The mechanism of 

 the initial transient vasodilatation and of the later 

 sustained one is plainly of great fundamental signifi- 

 cance. It will be convenient to consider first the na- 

 ture of the initial biphasic effect which is such a 



