1264 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



fig. 10. Effect of left sympa- 

 thectomy upon temperature of an 

 extremity after bilateral ligation 

 of iliac artery. On the side of 

 sympathectomy the temperature 

 is maintained. On the opposite 

 side it falls gradually to room 

 temperature but rises with great 

 rapidity at about the 8th hour 

 following the ligation. [From 

 Mulvihill & Harvey (125).] 



The idea that metabolites formed locally in anoxic 

 tissue can produce vasodilatation received early ex- 

 perimental support. Marey (115) had observed that 

 hyperemia occurred in the arm after a sufficient 

 degree of compression either by mercury (150-200 

 mm Hg) or in a pneumatic chamber. That this did 

 not require participation of the central nervous 

 system and that it was not the result of squeezing the 

 nerve itself was demonstrated by Bier (17, 18), who 

 noted reactive hyperemia after clamping and then 

 releasing the artery in the limb of a pig severed from 

 all connections with the body except for the major 

 vessels; compression of the nerve in another prepara- 

 tion produced no such effect. John & Warren (90) 

 showed that an increased flow was associated with 

 reactive hyperemia. Possible sources of error in 

 interpretation are that nerves intimately associated 

 with the arteries, or axone reflexes, might be in- 

 volved, or that a local myogenic conducting mecha- 

 nism might exist. Bier explained enlargement of the 

 major arteries on the basis of decrease in peripheral 

 resistance of the capillary bed. 



Controversy regarding chemical mechanisms in 

 collateral circulation was further stimulated by 

 Thomas Lewis's (98) dictum " — and we are brought 

 to ask if arterial growth is not directly controlled by 

 a stimulant, a chemical stimulant arising locally as a 

 product of tissue need and acting locally." If this 

 had no other good effect, it at least inspired a vigorous 

 investigation of the mechanisms of collateral circula- 

 tion, especially those related to arteriovenous fistula. 

 The primacy of mechanical over chemical phe- 



nomena, under some circumstances when both might 

 be operative, was suggested in the case of the ex- 

 tremity after ligature of a major artery by Winblad 

 et a!. (192), and by John & Warren (90), among 

 others, and in the case of arteriovenous fistula by 

 Holman (77) in his amputation experiment. 



Certain factors, such as anemia, exercise, and de- 

 creased arterial pO- 2 , can increase interarterial 

 anastomoses at least in the coronary system (45, 46, 

 197, 198). Just how this is brought about is not 

 known. 



The Clarks (33) had observed that the same 

 growth conditions which favored the formation of 

 new blood vessels also stimulated the growth of other 

 tissues in the same region. They were led to suggest: 

 "As for the chemical substance or substances which 

 may stimulate the formation of new capillaries, they 

 should be sought in embryonic tissue and in inflam- 

 matory exudates, since it is in such environments that 

 active vascular formation takes place." In autografts 

 of connective tissue in transparent chambers Williams 

 (190) concluded that hypoxia of a certain degree is a 

 stimulus for growth of vascular endothelium. No 

 specific data are given, however, to support this 

 statement. 



For the growth of vessels, Nothnagel (129) offered 

 a deceptively simple explanation: "'Anemia of 

 peripheral parts results in an increased flow through 

 collaterals, whereupon there is an augmented 

 nourishment of the walls of these vessels, by the mate- 

 rials with which they become increasingly perfused." 

 To substantiate this idea it is necessary to demonstrate 



