Hypoxemia and low Crs in vagally denervated lambs result from reduced lung volume and not pulmonary edema

Abstract

Vagal denervation performed in the intrathoracic region in newborn lambs leads to hypoxemia and decreased respiratory system compliance (Crs), which could result from atelectasis and/or pulmonary edema. The objective of the present study was to quantify the relative roles of alveolar derecruitment and pulmonary edema as underlying cause(s) of respiratory failure. Vagal denervation was performed in the intrathoracic region and below the recurrent laryngeal nerves in six newborn lambs within 24 h of birth, whereas six were sham operated. Pre- and postinflation Crs was measured to investigate the presence of alveolar derecruitment. Pulmonary edema was assessed with lung wet-dry-to-wet and lung tissue wet-to-dry ratios, total protein, and FITC-BSA recovery in lung tissue and bronchoalveolar lavage. Compared with that in the sham-operated animals, Crs was significantly lower in vagally denervated animals. However, postinflation, pulmonary system compliance obtained by quasi-static lung inflation and deflation to 30 cmH2O showed no significant difference between the sham-operated and denervated lambs. The lung wet-dry-to-wet and lung tissue wet-to-dry ratios, total protein, and FITC-BSA recovery in lung tissue and bronchoalveolar lavage were similar in denervated and sham-operated groups. We provide evidence that reduced lung volume and not pulmonary edema is associated with intrathoracic vagal denervation and is the likely underlying mechanism for hypoxemia and low Crs.

Afferent neural feedback overrides the modulating effects of arousal, hypercapnia and hypoxaemia on neonatal cardiorespiratory control

“…In a subsequent study, vagal denervation performed during the early postnatal period led to persistent hypoxaemia and apnoeas followed by respiratory failure within 24h post-denervation (Lalani et al 2001). Further investigations demonstrated that the mechanisms of respiratory failure included decreased functional residual capacity, attenuated expiratory braking, early suppression of augmented breaths, poor respiratory system compliance and atelectasis (Lalani et al 2001;Lalani et al 2002).…”

“…Establishment of pulmonary gas exchange is one of the most vital adaptations that must occur for the successful transition from fetal to neonatal life (Wong et al 1998;Greer et al 2006;Greer, 2012;Hooper et al 2015a;Hooper et al 2015b;Samson et al 2018). Evidence suggests that vagal innervation of the lung plays a critical role in establishing and maintaining adequate alveolar ventilation and pulmonary gas exchange during the early postnatal period (Fedorko et al 1988;Wong et al 1998;Harris & Milsom, 2001;Lalani et al 2001;Lalani et al 2002). However, the validity of some of these studies may have been compromised as a result of anaesthesia, possible secondary laryngeal obstruction and tracheostomy (Hasan et al 2000).…”

“…Furthermore, few studies have evaluated the role of afferent feedback in the immediate postnatal period. A number of studies have attempted to circumvent the limitations associated with the previous studies (Wong et al 1998;Lalani et al 2001;Lalani et al 2002). Wong et al (1998) reported that intrathoracic vagal denervation performed during the prenatal period caused fetal lambs to develop life-threatening respiratory failure at birth.…”

Congestive Heart Failure and Central Sleep Apnea

“…Importantly, there are other sensors in the lungs and circulation whose inputs modify the behavior of the respiratory control system, including pulmonary stretch receptors, irritant receptors, and the "J" (juxta-capillary) receptors which may become important in disease states and which are discussed below. (26)(27)(28)(29)(30) The concept of loop gain…”

A Century of Control of Breathing

“…Finally, Paintal (33) discovered that nonmyelinated vagal fibers had sensory endings in the walls of alveoli that sense lung water. These afferents were subsequently shown to provoke rapid, shallow breathing and increase lung volume during pulmonary vascular congestion (34), and to play a vital role in newborns by preventing atelectasis and ensuring adequate alveolar ventilation (35).…”