Fast breaths, slow breaths, small breaths, big breaths: importance of vagal innervation in the newborn lung.

IT IS WELL ESTABLISHED that vagally innervated mechanoreceptors in the lung influence respiratory frequency and the occurrence of spontaneous sighs (augmented breaths). Are these reflexes vitally important, or do they merely “fine tune” the respiratory pattern? The remarkable vitality and long-term survival of human patients and laboratory animals after denervation associated with lung transplantation argues for the latter (3, 7). The rapid onset of severe respiratory failure following vagotomy in neonatal animals argues for the former (5). In this month’s issue of the Journal of Applied Physiology, Lalani and associates (8) provide convincing evidence of the necessity of vagal pulmonary innervation for pulmonary function in lambs. This work extends earlier studies from their laboratory (15), which documented severe pulmonary failure at birth in lambs following denervation in utero. In the present work, the preservation of laryngeal innervation and absence of anesthesia eliminate confounding factors that were present in prior neonatal models. Moreover, the new study provides a wealth of physiological data that give important clues as to the cause of respiratory failure. Why was respiratory function so disastrously compromised in the denervated lambs? To answer this, it is important to separate the earlyfrom the late-occurring consequences of denervation. The earliest effects were slowed respiratory rate and decreased frequency of augmented breaths. These effects were associated with markedly decreased respiratory system compliance and prominent hypoxemia, which likely accounted for all later-occurring findings. Although the finer points of this generalization can be debated, the argument that extra pulmonary shunting and surfactant function were not the primary cause of the lambs’ demise (6) is accepted. What then is the explanation? In their present study, Lalani et al. (8) focus on the maintenance of lung volume, a major theme in neonatal respiratory control for the past 25 years. Previous studies have discovered an array of interdependent, vagally mediated mechanisms that function to increase both average and end-expiratory lung volume in newborns of several species, including humans (11). Lalani et al. perform an excellent review of this literature; however, some additional comments may be useful. The traditional thinking has been that the newborn needs a “dynamically” elevated lung volume because its chest wall, unlike that of the adult, has minimum outward recoil (1, 11). To offset this, adductor muscles increase laryngeal resistance during expiration. As a result, various respiratory patterns, including expiratory breath holding and its variations (“grunting”), are common in newborns, especially those with compromised lung function. In addition, the diaphragm and inspiratory interscostal muscles may remain partially or “tonically” active during expiration, thus stiffening the chest wall. It is generally accepted that these expiratory airflow “braking” mechanisms, combined with a relatively rapid respiratory rate, keep endexpiratory lung volume above what it would be if allowed to deflate to passive functional residual capacity (FRC). In Lalani and co-workers’ study (8), representative flow volume loops are shown for denervated and control lambs. The denervated lamb is shown to deflate to passive FRC, whereas the control lamb is shown to interrupt expiration with a breath before it reaches passive FRC. The passive expiratory time constant of the denervated lamb (slope of the flow volume curve, where volume is plotted as the ordinate) is shown to be much shorter than that of the control. Therefore, a shortened lung-emptying time combined with a prolonged expiratory time can explain the reduced lung volume in denervated lambs. The question of how laryngeal muscle activity might have affected this finding is not answered, as the larynx was bypassed to measure respiratory system mechanics. Did the denervated lambs grunt or perform breath hold maneuvers? This was not discussed in the study of Lalani and