Heart, Blood Vessels, Blood, and Entodermal Derivatives 



451 



be identified as such by available technical 

 methods. Since the vasoformative cells arise 

 in diverse embryonic regions, it is difficult 

 to devise experiments to test the time of 

 their determination. However, it is not im- 

 probable that some mesodermal cells are de- 

 termined for endothelium by the end of 

 gastrulation (at a time when other meso- 

 dermal cells are determined for other pri- 

 mordia such as heart, limbs, et cetera). If 

 this view of an early determination is cor- 

 rect, it becomes easier to harmonize angio- 

 genesis in the lower vertebrates with that 

 in mammals. In macaque and human chor- 

 ions, endothelium and mesoderm differen- 

 tiate simultaneously from cytotrophoblast, 

 according to Hertig ('35). Although the 

 early differentiation of vascular endothelium 

 in man and other mammals is well estab- 

 lished, Hertig's interpretation that endo- 

 thelium arises directly from cytotrophoblast 

 is not universally accepted (Bloom and 

 Bartelmez, '40). 



There is no experimental evidence for a 

 vieW' that the early intraembryonic endo- 

 thelium arises by ingrowth from the extra- 

 embryonic endothelium of the yolk region. 

 Explants and heterotopic transplants of 

 cardiac and other organ primordia develop 

 endothelium in situ. Neither is there any 

 evidence for the unusual view that endo- 

 thelium of the branchial and head vessels 

 arises by outgrowth from the heart. The 

 chief embryonic vessels develop when heart 

 formation is prevented by extirpation of pre- 

 sumptive heart mesoderm in amphibians. 

 Experimental evidence for in situ formation 

 in mammals is seen in the development of 

 blood vessels from mesenchyme in explants 

 of the allantoic bud from rat embryos (Jolly, 

 '40). 



The earliest vessels in union with the 

 heart — the truncus arteriosus and the ce- 

 phalic portions of the vitelline veins — arise 

 in a manner resembling the formation of 

 endocardium. Cells of mesodermal origin 

 aggregate in the pathways of the future ves- 

 sels and differentiate into primitive endo- 

 thelium. As the vessels are traced progres- 

 sively from the heart, the strands of 

 vasoformative cells become progressively 

 more irregular in their pattern and form 

 elaborate capillary networks. The arteries 

 and veins arise by enlargement and 

 differentiation of pathways through the net- 

 work. This mode of development is found 

 even in parts of the aortae and cardinal veins 

 (Evans, '08; Sabin, '17). An exception to the 



formation of vessels from a primitive net- 

 work is found in the opossum brain (Wis- 

 locki, '39). In this species, the cerebral 

 arteries are non-anastomotic "end-vessels," 

 and from the time of their first appearance 

 these arteries and their corresponding veins 

 show their characteristic adult plan. 



The pattern of the vascular system is de- 

 pendent upon several factors. Hereditary fac- 

 tors supposedly play an important part in 

 the formation of the earliest vessels (aorta 

 and large veins) which develop before cir- 

 culation begins. Many vessels will undergo 

 a fairly extensive development when circu- 

 lation is prevented — for example, after 

 cardiac extirpation (Knower, '07; Clark, '18; 

 and others). It is obvious that the mechani- 

 cal effects of circulation cannot apply to 

 vascular development under these condi- 

 tions. On the other hand, the inherent pat- 

 tern of the earliest vessels may be dependent 

 upon mechanical and chemical effects from 

 other embryonic tissues. 



Chemical and mechanical factors associ- 

 ated with blood flow (function) affect the 

 further development of the vascular system 

 after the embryonic circulation becomes 

 established. Clark ('18) suggested that the 

 formation of new vascular sprouts is influ- 

 enced by the amount of interchange through 

 the walls of the vessels — interchange be- 

 tween blood and surrounding tissues. Thus 

 the growth and metabolism of outside tis- 

 sues may control the outgrowth of new 

 vessels. Streeter ('18, '27) also stressed the 

 importance of the endothelial environment 

 and stated that the embryonic vessels do 

 not have a ground plan of their own. In 

 this connection, some observations by 

 Scharrer ('39) are of particular interest. He 

 found that the end-vessel pattern character- 

 istic of the opossum brain will develop in 

 dead brain tissue and he interpreted this 

 finding as evidence for a factor inherent to 

 the cerebral vessels themselves. On the other 

 hand, Wislocki ('39) believes the result can 

 be explained by an environmental factor 

 present even in the dead tissue. 



The amount of blood flow through a capil- 

 lary, rather than the rate of flow, determines 

 whether a given capillary within a mesh- 

 work atrophies, remains a capillary, or en- 

 larges to form an arteriole or venule (see 

 Clark's '18 analysis of Thoma's laws). Clark 

 and Clark ('40) find that the differentiation 

 of adventitial cells into smooth muscle is 

 influenced by blood pressure and thus they 

 confirm the histomechanical principle of 



