Effect of bilateral vagotomy on oxygenation, arousal, and breathing movements in fetal sheep

Abstract

To investigate the effects of bilateral cervical vagotomy on arousal and breathing responses, we studied eight sham-operated and eight chronically instrumented unanesthetized vagotomized sheep fetuses between 136 and 144 days of gestation (term approximately 147 days). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, blood pressure, pH, and blood gas tensions. In a randomized order, fetal lungs were distended with four different O2 concentrations: 0 (100% N2), 21, 50, and 100% at a continuous positive airway pressure of 30 cmH2O via an in situ Y-endotracheal tube. Under control conditions, inspiratory time and the duration of the single longest breathing episode decreased from 598 +/- 99 (SD) ms and 24 +/- 10 min in sham group to 393 +/- 162 ms and 11.0 +/- 3.0 min in vagotomized group (P = 0.04 and 0.033), respectively. In response to lung distension with 100% N2, breathing time decreased from 44 +/- 17 to 20 +/- 18% (P = 0.045) in sham-operated fetuses, whereas it remained unchanged in the vagotomized group. In response to 100% O2, fetal arterial PO2 increased in five of eight fetuses sham-operated from 18.2 +/- 5.1 to 227 +/- 45 Torr (P = 0.0001) and in six of eight vagotomized fetuses from 18.5 +/- 4.4 to 172 +/- 39 Torr (P < 0.001). Although arousal was observed in all oxygenated fetuses at the onset of breathing, the duration of arousal was markedly attenuated in vagotomized fetuses (14 +/- 10 vs. 46 +/- 29 min in sham group; P = 0.024). Frequency and amplitude of breathing and respiratory output (frequency x amplitude) increased only in sham group (P = 0.02, 0.004, and 0.0002, respectively). We conclude that in response to lung distension and oxygenation, arousal and stimulation of breathing during active and quite sleep are critically dependent on intact vagal nerves.

Physiological Society Symposium – Vagal Control: From Axolotl to Man

“…(1974) showed that vagal denervation or blockade of nerve conduction had no significant effect on the size, frequency or incidence of fetal breathing movements (FMBs). Similarly, in our previous study, no significant effect on the overall incidence of FBMs was observed in the vagally denervated fetal sheep although individual episodes and inspiratory times (T,) were shorter as compared with the sham-operated group (Hasan & Rigaux, 1992).…”

“…198 1;Hasan & Rigaux, 1992) examined only the short term effects of vagal innervation on breathing patterns. It is not clear whether the removal of vagal afferent feedback over a relatively long period would have an impact on the central respiratory pattern generator since the nucleus tractus solitarius (NTS), one of the four vagal nuclei, receives critical rhythm modulatory and regulatory afferents from upper and lower respiratory tracts.…”

Postnatal development of right atrial injection of capsaicin-induced apneic response in rats

“…Second, premature birth did not significantly alter the vagal Hering-Breuer reflex in lambs 2, and the PCF-mediated respiratory responses already existed in newborn lambs (2) and rabbits (15). Third, breathing movements are episodic in fetal life and abruptly change to be continuous after delivery, but continuous breathing is critically dependent on fetal maturity and intact vagal nerve function (21,54). For example, the consequences of bivagotomy were more dramatic in the newborn anesthetized and decerebrated cats, dogs, and kittens compared with the older ones, including a greater prolongation of TE, possibly leading to death within a few hours (12,50).…”

Vagal nerve maturation in the fetal lamb: An ultrastructural and morphometric study

“…The treatment of these disorders has been largely symptomatic due to incomplete understanding of the basic mechanism involved in the control of neonatal breathing. Breathing movements are episodic in fetal life and abruptly change to be continuous after delivery, but continuous breathing is critically dependent upon fetal maturity and intact vagal nerve function (Hasan and Rigaux, 1992).…”