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HANDBOOK (J1- I'HYSIOI.OOY 



CIRCULATION II 



operative varies among the species. The earlier 

 work is described by Barcroft (25) and the later by 

 Dawes and his colleagues (39, 70, 71, 74). 



The responses to asphyxia and to the intravenous 

 administration of hormones have been most gener- 

 ally used to determine the activity of the cardio- 

 vascular system in the fetus: the low resistance of the 

 placenta, the low arterial oxygen tension, and the 

 fetal course of the circulation must also influence the 

 final operation of the reflexes. Quantitative data are 

 difficult to obtain when both the peripheral and cen- 

 tral mechanisms have not yet reached a steady rela- 

 tionship with each other. However, in the lamb, the 

 steeper rise in arterial pressure which occurs from 

 90 days onward approximately coincides with the 

 development of increasing responsiveness to asphyxia, 

 as judged by the rise in arterial pressure and heart 

 rate (39) : further, the removal of sympathetic tone, 

 following the injection of a ganglion-blocking agent 

 such as hexamethonium causes a greater fall of 

 blood pressure toward term. The tone of the vasomo- 

 tor mechanisms is probably not fully developed at 

 birth for the mean arterial pressure is about 40 mm 

 Hg lower than in the adult sheep. In the rabbit, 

 cat, and dog, with low arterial pressures at term, the 

 vasomotor mechanisms are probably still less de- 

 veloped at birth (70, 1 14). 



The pattern of the response of the developing 

 cardiovascular system to asphyxia alters with gesta- 

 tional age. The bradycardia which follows either the 

 occlusion of the umbilical cord or the administration 

 of low oxygen tensions to the mother is probably 

 brought about in a variety of ways. In the early fetus 

 of all species cardiac slowing is delayed, it is due to 

 the direct effect of the hypoxia on the pacemaker 

 and is the cause of the ensuing hypotension; this 

 depression of the pacemaker is the final cause of 

 death at any age when hypoxia is prolonged. Later in 

 development, a transient bradycardia of swift onset 

 is observed, which is due to stimulation of the medul- 

 lary vagal center; later still, this slowing is succeeded 

 by a tachycardia, due to stimulation of the medullary 

 sympathetic center. This response is enhanced by 

 cutting the vagus nerves. The third type of brady- 

 cardia is reflex in origin and occurs in response to 

 the rise in blood pressure when vasomotor, baro- 

 receptor, and chemoreceptor activity is developed; 

 the bradycardia seen in the fully developed lamb or 

 human fetus is probably reflex in origin provided the 

 asphyxia is of short duration. It is noteworthy that 

 prolonged asphyxia or hypoxia reduces the heart 

 rate to between 60 to 80 beats per min in most species; 



this rate is sustained for varying periods before ar- 

 rhythmia occurs. Both the tachycardia and the 

 reflex bradycardia during asphyxia may be enhanced 

 by the activity of the adrenal medulla (54). Bradv- 

 cardia is also the primary response to hypoxic stimu- 

 lation of the chemoreceptors in the adult animal (60, 

 61); however, if the brain is also hypoxic, tachycardia 

 usually results from hypoxia of these areas and this 

 tachycardia is enhanced it their oxygen supply is 

 increased. 



Quantitative data relating the oxygen saturation 

 of the fetal blood at which the changes in heart rate 

 take place in utero have been provided in the near- 

 term lamb by Born et til. (39), and by Reynolds & 

 Paul (161). These observers are not entirely in 

 agreement with each other; both administered 

 nitrogen containing low concentrations of oxygen to 

 the mother under barbiturate anesthesia. Born el al. 

 delivered their lambs by Cesarean section and ob- 

 served an increase in heart rate and blood pressure 

 during the administration of 7.5 to 5.0 per cent oxy- 

 gen to the mother which caused the fetal carotid 

 arterial oxygen saturation to fall to 50 to 35 per cent; 

 bradycardia did not occur until the arterial oxygen 

 saturation was below 20 per cent for some minutes 

 (fig. 9). Reynolds and Paul's lambs were kept in 

 utero and blood pressures and blood samples were 

 obtained from branches ot the umbilical vessels 

 exposed through a small uterine incision. Their 

 results were not so clear cut for fetal tachycardia or 

 bradycardia might be observed following the ad- 

 ministration of 13 per cent and 10 per cent oxygen 

 to the mother and 6 per cent oxygen usually caused 

 fetal bradycardia; it is to be noted that the adminis- 

 tration of 13 per cent oxygen reduced the arterial 

 oxygen saturation to 30 per cent, a figure which was 

 obtained by Born et til. with much lower oxygen mix- 

 tures. In the guinea pig, also anesthetized with 

 Nembutal, the administration of 10 per cent oxygen 

 to the mother caused a slight fall in fetal heart rate, 

 during the last third of gestation, while 6 per cent 

 oxygen always caused marked bradycardia (97, 133). 



The absence of cardiac acceleration in response to 

 asphyxia early in gestation is not due to the inability 

 of the young heart to increase its rate, for it will 

 respond to adrenaline early in development: in the 

 lamb the heart is more sensitive to adrenaline than 

 are the peripheral vessels for tachycardia occurs at a 

 time when the increase in pressure is relatively small; 

 later the rise in blood pressure is greater and the 

 increase in heart rate diminished, due to the de- 

 velopment of baroreceptor reflex activity (74)- Acetyl- 



