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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



major nutrient artery was ligated, but that in time 

 there was a prodigious growth of new vessels (146). 

 He was not the first to observe this providential 

 activity of nature, since Antyllus, a pioneer in the 

 surgical treatment of aneurysms fifteen centuries 

 before him, had noted that interruption of the artery 

 to a limb does not necessarily result in its loss (97). 

 Morgagni also had anticipated Hunter in observing 

 collateral vessels. After numerous experiments Hunter 

 could conclude only that "vessels go where they are 

 needed'' ( 124). 



In attempting in this chapter a precis of some 

 major advances in the understanding of this complex 

 subject a sense of wonder and frustration still remains. 

 Scholarly reviews have been published by Mulvihill 

 & Harvey (124), Quiring (139), Longland (108), 

 Learmonth (96) and Rati <!v Schoop (141) among 

 others. Here it will be necessary to consider chieflv 

 what is known of general principles, and little con- 

 sideration can be given to specific collateral beds. To 

 the coronary circulation detailed consideration has 

 been given by Spalteholz (164), Gross (64), Gregg 

 (63), Schlesinger (155), and very recently by Blum- 

 gart (21 ), Pepler & Meyer (133) and Laurie & Woods 

 (95). The pulmonary collaterals have been investi- 

 gated by Miller (121) Berry & Daly (15), Verloop 

 (180, 181), State et al. (166, 167), Parker & Smith 

 (132), Tobin (175), Tondurv & Weibel (177) and 

 by Liebow et al. (101, 103) among others. A recent 

 study of hepatic collateral circulation has been pub- 

 lished by Hales et al. (68). 



Some Aspects of Angiogenesis in General 



A brief review of the painstaking observations upon 

 angiogenesis by such devoted students as Golubew 

 (58), Thoma (174), Evans (48, 49), Sabin (150), 

 Hughes (81, 82), and the Clarks (31-37) might well 

 serve as a guide to approaching the problems of the 

 developing collateral circulation. 



In embryos there is an initial phase of primary 

 differentiation of vessels from connective tissue cells, 

 and a later stage of extension and elaboration. The 

 latter occurs from endothelium of vessels already 

 formed by a process of "sprouting," and comes largely 

 if not entirely to replace the former. Certainly most of 

 the vascularization of the developing organs of the 

 embryo, such as the limb buds of birds, occurs by 

 ingrowth of sprouts and not by formation de novo of 

 vessels within the tissue (48, 49, 150). As early as 

 1869 Golubew (58) observed in the transparent tail 



of the living tadpole that the capillary sprouts were 

 at first solid but then developed a lumen by a process 

 of "hollowing out" beginning proximally as vacuola- 

 tion. The development of new capillaries by sprouting 

 was further studied soon thereafter by Arnold (5, 6). 

 E. R. Clark (31) in the same subject noted atrophy of 

 certain newly formed capillaries. Aeby's (2) concept 

 that the anlage of the entire vascular system was 

 represented by capillaries in retiform arrangement 

 received strong support from the study of injected 

 and serially sectioned embryos by Evans (48). 



It has been established that vessels destined to 

 become major conduits for blood in the adult can 

 differentiate to a limited but recognizable degree 

 even in the absence of circulating blood. This was 

 known to such early embryologists as Baer and His, 

 and was studied in greater detail by Sabin (150). 

 Experimental support was provided by Loeb (107), 

 who stopped the heartbeat in fundulus larvae chemi- 

 cally, and later by Chapman (28) when he removed 

 the heart in chick embryos. The aorta and certain 

 other main arteries and veins nevertheless become 

 recognizable. Presumably, this limited self-differentia- 

 tion of the vascular system is determined by hereditary 

 factors. 



Thoma (174), long a student of responses of the 

 vascular system, understood these influences, but to 

 him is due the credit of recognizing the molding force 

 of the circulating blood. He observed, during the 

 first 3 days of development of the area vasculosa of 

 the chick, that certain pathways of most rapid blood 

 flow increased in caliber and length and thereby ac- 

 quired the characteristics of magistral vessels, while 

 others underwent diminution and atrophy. He codi- 

 fied the principles of what he termed histodynamics: 

 a) The growth of the lumen of a vessel, that is the 

 increase in surface of the wall, depends upon the 

 rate of blood flow, b) The growth in thickness is 

 dependent upon the tension in the wall, which in turn 

 is related to the diameter of the vessel and to the blood 

 pressure, c) It is an increase in blood pressure above a 

 certain level, which limit is defined by the metabolism 

 of the particular tissue, that determines the new 

 formation of capillaries. The formulation of the 

 principles, although they have not been universally 

 accepted in toto, has stimulated much thought. The 

 factor causing enlargement of an artery was, for 

 example, thought by Clark (31) to be the amount of 

 blood flow rather than the rate as suggested by 

 Thoma (174). Clark proposed the hypothesis that 

 when the chemical interchange through the wall of 



