Effects of Hypoxia and Acidity on the Initiation of Breathing in the Fetal Lamb at Term

Abstract

DESPITE their immense importance, the factors initiating respiration at birth are incompletely understood. The classic theory has been that respiration is initiated as a result of sensory stimulation of the baby as it passes through the birth canal and encounters the cooler, external environment. If this fails to elicit respiration, then asphyxic stimulation, acting through peripheral chemoreceptors, may be activated as an emergency mechanism to restore the depressed infant by induction of gasps.Since all infants undergo a degree of asphyxiation at birth, it was believed that a study of the effects of fall in fetal Po2 and pH and rise in fetal Pco2 on the initiation of respiration, under conditions where the fetus was not subjected to other stimulation, might indicate whether asphyxic stimulation is an emergency mechanism or actually a physiologic part of the initiation of breathing. Gas mixtures were administered to term ewes, and the Po2, Pco2, and pH were recorded continuously in the brachial artery of fetal lambs with intact umbilical circulation.1 Neither marked hypoxia per se nor marked hypercapnia, produced in this manner, initiated respirations, but a com¬ bined stimulus of low P02 and high Pcoo invoked breathing of the lambs. Plowever, the administration of hypoxic and hypercarbic gas mixtures to the ewes resulted in severe compromise of the umbilical blood flow. Since deliberate clamping of the um¬ bilical cord of the term fetal lamb is always followed by respiratory efforts,2 we could not ascertain whether the onset of breathing of these lambs was related to the hemodynamic changes induced or to the altera¬ tions in fetal gas tensions. To exclude interference with the umbili¬ cal circulation and to avoid other changes in fetal hemodynamics, experiments involving perfusion of the carotid artery were de¬ signed in the manner to be described.The purpose of this article is to present these experiments and several other studies which may contribute to an understanding of some of the mechanisms of the initiation of respiration and to offer an hypothesis which is compatible with most of the empiri¬ cal and experimental observations that have been made up to the present time. Methods and MaterialsFetal lambs at term were studied by methods modified in certain respects from those reported previously.2 The methods used generally will be described first and then the special methods per¬ taining to four groups of experiments will be de¬ tailed along with the experimental results.General Methods.-After anesthesia (2 cc of 1% tetracaine) was administered into the subarachnoid or epidural space in the lower lumbar area, the ewe was secured on her side on the operat¬ ing table. The left femoral artery was catheterized so that maternal blood was available for P02, Pcos, and pH determinations, and as a bank for appro¬ priate transfusions or perfusions of the fetus. An incision was made in the ewe's anterior abdominal wall, near the midline. After a hysterotomy was performed, the fetal head was palpated in utero, was del...

Hypoxic apnea and gasping.

“…Animal studies of apnea and gasping are infrequent as well, and usually include experiments on fetuses, inReceived for publicationt 25 September 1974 and in revised form 12 Autgust 1975. volving the first breath. The basis for apnea before birth has not been proven; the first breath at birth has been thought to involve either hypercarbia or hypoxia or both (3,4).…”

Respiratory Effects of Division of the Carotid Sinus Nerve in the Lamb Soon After the Initiation of Breathing

“…In addition to chemoreceptor fibers, baroreceptor fibers were divided, as were some postganglionic sympathetic and pressure receptor fibers, the functions of which have not been clearly defined [2]. Although baroreceptor potentials are very active in the carotid sinus nerve of the newborn lamb [8], severance of this nerve produced no significant change in heart rate; the inconsistent and slight increase in blood pressure recorded would not be expected to produce reflex effects on breathing.…”

“…Tonic chemoreceptor activity has been difficult to demonstrate in the fetus, but several investigators have proposed that even before birth the carotid body is functional [3,4,8,13]. In contrast, a striking increase in chemoreceptor activity has been recorded from the carotid sinus nerve of the lamb delivered by hysterotomy at the time when the umbilical cord was clamped [7,8,13]. This disparity might be explained by potentiation of chemoreceptor activity by the rapid rate of chemical change after cord occlusion [1] or by a critical diminution in blood flow through the carotid glomus.…”

“…Seven lambs at term were delivered by hysterotomy from ewes given spinal anesthesia by methods previously described [6,8]. The fetal head was delivered through a small incision in the uterine wall and was capped with a water-filled rubber glove to prevent ventilation.…”

“…These chemical changes may play a significant role in initiating respiration. Recent experiments have indicated that the carotid chemoreceptors are activated following occlusion of the umbilical cord of the term lamb delivered by hysterotomy [7,8,13] and are important in initiating the effective respiratory efforts needed for survival [6].…”