Asphyxia neonatorum: An experimental study in the guinea pig

Abstract By clamping either the uterine vessels or the umbilical cords, it was possible to induce intrauterine anoxia experimentally in guinea pig fetuses at or near term. Prior to this procedure the mother's abdomen had been anesthetized locally and one fetus delivered to serve as a control animal. Fifty-eight asphyxiated fetuses were delivered as soon as intrauterine respiratory movements, induced by the anoxia, became weak or had just ceased. Forty-five other fetuses were delivered some minutes after the cessation of intrauterine respiratory efforts, and resuscitation in this group was delayed until the fetal heartbeat was weak and often too feeble to palpate. Anoxia thus induced led to the characteristic picture of asphyxia pallida; namely, apnea, bradycardia, atonia, cold pale skin, and dilation of the visceral capillary beds. The only effective method of resuscitating such apneic fetuses was to inflate the lungs rhythmically and gently with oxygen or with oxygen containing 10 per cent carbon dioxide. Respiration was established sooner with the gas mixture than with oxygen alone. All efforts to revive fetuses by mechanical or electrical stimulation or by the injection of respiratory stimulants proved ineffectual. The behavior of resuscitated animals was compared with that of their litter mate controls until overt differences were no longer noticeable. The animals were then subjected to a modified maze situation in order to discover possible impairment of learning ability resulting from anoxial damage to the central nervous system. When all observations and tests were completed, the brains of the experimental animals and their controls were removed and prepared for histologic study. The following statements summarize the results of experimentally induced asphyxia neonatorum in guinea pigs: 1. 1. Respiratory movements in utero continued longer after clamping the uterine arteries than the umbilical cord. This findings is related to the total volume of oxygenated blood available to the fetus; there is a placental reserve when the uterine vessels are clamped. 2. 2. Within two minutes after clamping the uterine or umbilical vessels the heart slowed to half its normal rate. The heart could be palpated for twelve to fifteen minutes after clamping but grew progressively weaker and slower with prolonged anoxia. When oxygen or oxygen-carbon dioxide were administered, there was an immediate return in strength and rate of the heart. Acceleration from this point on was not gradual but saltatory, further increments coinciding with the appearance of visceral movements, urine passage, muscular twitching, improvement of thoracic tonus and finally a last increase as breathing began. 3. 3. It required fifteen to eighty minutes to resuscitate apneic fetuses but the nature of initial respiratory responses varied with the gas used. Respirations did not begin spontaneously with oxygen alone until after the nervous system had recovered sufficiently to allow afferent vagal and spinal impulses to affect the respiratory center reflexly. Ten per cent carbon in oxygen brought about a spontaneous response of the respiratory center sooner than oxygen alone, and before the center could be made to respond reflexly. 4. 4. Asphyxiated guinea pigs lost more weight in the first three days of life than did their litter mate controls. Their weight average over the first four weeks also was lower than the average of controls. 5. 5. All asphyxiated animals exhibited symptoms of neural damage for shorter or longer periods after birth. The following phenomena were noted: (1) weakness and fremors; (2) delayed and incoordinated efforts to right; (3) flaccid paralysis, particularly of the hind limbs and often lasting for several days; (4) spastic paralysis, particularly of forelimbs and accompanied by opisthotonos; (5) convulsive twitehing and rhythmical running movements; (6) epileptiform convulsions; (7) paralysis of extraocular muscles, facial motor weakness, and some loss of control over tongue and pharyngeal muscles; (8) early hyperesthesia followed by hyposensitivtiy; (9) somnolence and reduced activity levels; (10) perhaps some impairment of hearing and vision. The degree of injury and its site varied from animal to animal in a fortuitous manner; there was no precise correlation between the duration of anoxia and the severity of damage. 6. 6. Asphyxiated guinea pigs exhibited noticeable behavioral differences when compared with control animals during the first two weeks. In general they were not greatly disturbed by changes in their environment. They became quite docile and were flaccid when handled. Loud sounds did not elicit the normal startle response. They did not respond briskly to faradic stimulation. Many of them presented feeding problems and were weaned on cow's milk, a food which the controls refused to take. They were not as active as normal guinea pigs and were not as tense and irritable in learning situations. 7. 7. When confronted with a simple maze and alternation problem, the asphyxiated animals made more errors and duplicated the same errors more frequently than did their litter mate controls. Even in correct trials their behavior was remarkably stereotyped and showed little of the plasticity and variation encountered in the responses of the control animal. 8. 8. The central nervous system of 65 per cent of the experimental animals studied to date showed histopathologic changes. All control brains were normal and only questionable or slight pathologic findings could be seen in the remaining asphyxiated animals. Changes in the first few days after anoxia had been induced included early disseminated necrosis, edema, chromatolysis, scattered petechial hemorrhages and enlargement of the ventricles. Glial proliferation appeared by five days and was marked at nine days. In older specimens loss of nerve cells led to local or generalized atrophy of the brain. Destruction of pyramidal cells in the cerebral cortex was observed. Necrosis and atrophy were not always related to hemorrhages.