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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



But the morphogenesis of heart chambers can only 

 take place "in embryo" demonstrating, again, the 

 probable importance of spacial factors in develop- 

 ment; striated myofibrils are present by the time the 

 contractile activity is sufficient to circulate the blood. 

 Ebert (86) has shown by immunochemical techniques 

 that cardiac myosin, similar to that found in the 

 adult, is widely distributed in the very early embryo 

 and that the restriction of the heart-forming area 

 during development is accompanied by a limitation 

 of the synthesis of this specific protein and the com- 

 mencement of the capacity for synthesis in these 

 areas. These facts do not explain the first appearance 

 of myosin or actin, the origin of the nonpropagated 

 contractions which begin in the ventricles, or the 

 probable dependence of the developing cardiac mus- 

 cle metabolism chiefly upon anaerobic glycolysis 

 (>77)- 



Congenital Malformation 



A knowledge of the metabolic processes responsible 

 for embryonic differentiation would provide the 

 foundation for a better understanding of the causes 

 of congenital malformation and help to enable their 

 prevention. In human pediatrics, congenital ab- 

 normalities appear in 1 per cent of all live births 

 (162) and now contribute to 20 per cent of the neo- 

 natal deaths in countries where the infant death rates 

 are low (185); malformation of the cardiovascular 

 system is second to malformation of the nervous sys- 

 tem in causing this mortality. The causes of congenital 

 abnormality may be genetic but are chiefly due to 

 environmental factors (147) and there is a wealth of 

 descriptive information on the influence of a wide 

 variety of experimental procedures and chemical 

 substances which are teratogenic (119); each is usu- 

 ally effective at a certain stage of development and 

 may influence the organogenesis of one or a number 

 of the systems. Abnormalities of the cardiovascular 

 system in human infants are mainly associated with 

 the rubella virus: in the experimental animal meta- 

 bolic inhibitors and nutritional deficiencies of the 

 mother, especially of the vitamins, may produce 

 abnormalities; the high concentration of riboflavin 

 in fetal blood and the transfer mechanism which 

 exists in the placenta for this vitamin is probably 

 related to its high requirements in fetal metabolism 

 (131). Acute anoxaemia, due to maternal exposure 

 to carbon monoxide gas is known to be teratogenic 

 in the human infant (115) but chronic hypoxia, 

 though it may be effective in animals (119), is diffi- 



cult to establish as teratogenic in the human. The 

 incidence of congenital malformation of the cardio- 

 vascular system is no greater in infants born to women 

 living at high altitudes than it is at sea level (147), 

 demonstrating that the adaptive processes enabling 

 life at lower oxygen tension also ensures an adequate 

 oxygen supply in developing tissues. Another aspect 

 of chronic hypoxia, reduction in maternal placental 

 blood flow, probably has most important conse- 

 quences for the infant in such conditions as toxemia 

 of pregnancy: in animals a reduced maternal placen- 

 tal blood supply causes "runting" and the over-all 

 size of the fetus is small, but there appear to be no 

 definite congenital abnormalities (132); this may 

 possibly be explained by the reduction in supply of 

 nutritive material without any alteration in balance 

 of the essential constituents. These epidemiological 

 and etiological facts cannot, yet, explain why only 

 5 to 30 per cent of the infants, born of mothers in- 

 fected with rubella during the first trimester, de- 

 velop malformations of the cardiovascular system 

 (95) or why the disturbance of organogenesis presents 

 itself in diverse forms. For example, why does normal 

 but misplaced growth of the large blood vessels 

 occur? What stimulates growth of the septum secun- 

 dum causing premature closure of the foramen ovale 

 and why is there too little reabsorption of the septum 

 spurium leaving Chiari's net (144)? 



COURSE OF THE CIRCULATION IN THE FETUS 



The probable course of the fetal circulation in the 

 mammal, once the major channels have developed, 

 is illustrated in figure 5. The most arterial blood 

 circulates from the placenta, in the umbilical vein, 

 to the liver which it perfuses; this blood leaves the 

 hepatic vein to join venous blood from the caudal 

 part of the body in the inferior vena cava. In some 

 species, notably the human, the monkey, and the 

 sheep, a proportion of the blood in the umbilical 

 vein short-circuits the liver and passes straight into 

 the inferior vena cava through the ductus venosus. 

 As it enters the heart the inferior caval stream is 

 divided by the crista dividens of the foramen ovale 

 (fig. 6) ; most of the blood flows straight into the left 

 auricle, where it mixes with a small volume of pul- 

 monary venous blood and passes into the left ven- 

 tricle, whence it is pumped mainly to the head and 

 upper extremities. A smaller stream of inferior caval 

 blood is directed to the right auricle, mixes with ve- 

 nous blood from the coronarv sinus and from the 



