Effects of Carotid Body Maturation and Terbutaline on the Laryngeal Chemoreflex in Newborn Lambs

Abstract

ABSTRACf. The response to laryngeal chemoreflex (LCR) water stimulation was compared in unanesthetized awake 4-to 10-day-old preterm and 2-to 4-wk-old term lambs before and after infusion of a ,B-adrenergic agonist, terbutaline, given pre-and postcarotid body denervation (CBD). Ventilation decreased more in response to LCR stimulation post-CBD in the older lambs. CBD did not change the respiratory response to LCR stimulation in the younger lambs. LCR stimulation resulted in less bradycardia post-CBD in both groups. Terbutaline significantly attenuated the LCR response in the older lambs pre-CBD but not post-CBD. LCR respiratory response was not changed in the younger lambs when terbutaline was infused, pre-or post-CBD. Compared to wakefulness, the LCR response in preterm lambs was greater in sleep not associated with arousal. If arousal occurred, LCR response during sleep did not differ from that during wakefulness. The incidence of arousal decreased markedly after CBD, suggesting that arousal is modified by the carotid bodies. It is concluded that the carotid bodies modify the reflex response to LCR stimulation in 2-to 4-wk-old lambs. During the 1st postnatal wk, preterm lambs have a reduced carotid body function during wakefulness and, therefore, a decreased hypoxic ventilatory response and increased respiratory response to LCR stimulation. The attenuating effect of terbutaline on LCR response is partially related to mature carotid body function. (Pediatr Res 20: 724-729, 1986) Abbreviations CBD, carotid body denervation LCR, laryngeal chemoreflex Reflex apnea from stimulation ofthe LCR has previously been described in several animal species (1-3) and in human infants (4). The reflex is thought to be a protective mechanism through which animals and humans can preserve vital functions while they are not breathing. Laryngeal water stimulation elicits apnea, swallowing, hypertension, bradycardia, and blood flow redistribution in the "diving seal" pattern (2, 5). The respiratory response is associated with a decrease in arterial oxygen tension which should stimulate arterial chemoreceptors. In a previous study (2), we demonstrated a decrease in the cardiovascular response to Received April 15, 1985; accepted March 17, 1986. Correspondence and reprint requests should be addressed to Dr. Jens Grogaard, Department of Pediatrics, Vanderbilt University, School of Medicine, Nashville, TN 37232.This research was supported by grants from the National Institute of Health (RR 5424-21 and HL 14214) and March of Dimes Birth Defects Foundation (1-739).LCR stimulation during hyperoxia and proposed that part of the cardiovascular response to laryngeal water administration in newborn lambs might be due to stimulation of arterial chemoreceptors. Postnatal age appears to be an important factor in the LCR response. The respiratory response to LCR stimulation is markedly diminished in the adult animal compared to the newborn of the same species (3). A postnatal maturation effect has been demonstrated on the carotid body mediated ...

Prolonged Hypoxemia Enhances and Acute Hypoxemia Attenuates Laryngeal Reflex Apnea in Young Lambs

“…The ventilatory response to acute hypoxia increases progressively during the first 2 postnatal weeks and is related to maturational changes in the peripheral chemoreceptors principally located in the CB (14). The greater ventilatory inhibition in response to LCR stimulation in the first postnatal weeks may be related to a reduced CB sensitivity to changes in Pao2 (14).…”

“…Using aseptic technique and local anesthesia, 3-d-old lambs were instrumented with placement of a low tracheostomy and catheters in the cranial tibial artery and lateral saphenous vein, as described previously (14). A 2-inch segment of an endotracheal tube (Portex, Inc., Wilmington, MA) was inserted into the tracheostomy to allow the lambs to breath through the upper airway except for at the time of the studies.…”

“…Others have also shown an age-related decrease in the LCR response (2,(14)(15)(16), but the mechanism inducing the maturational changes remains obscure. There is evidence showing that, in sheep, laryngeal receptor properties are unaffected by age (9) and afferent activity from laryngeal receptors is much the same in newborn and adult animals (6).…”

“…The role of the peripheral chemoreceptor needs to be considered, inasmuch as the LCR apnea response is associated with a decrease in Pao2, which stimulates peripheral chemoreceptors ( 13). CB denervation significantly increased the apnea response after laryngeal stimulation in 2-to 4-wk-old lambs, but this response remained unchanged in younger lambs, suggesting that a mature CB function plays a role in limiting reflex apnea caused by laryngeal water stimulation (14). However, it has been postulated that acute hypoxia preceding apnea induces a positive feedback that reinforces suppression of breathing, a mechanism that may play a role in the etiology of SIDS (2,5,20).…”

“…The response is characterized by apnea, swallowing, btadycardia, hypertension, and blood flow redistribution (1 3). The magnitude of the response decreases with maturation (14)(15)(16). Electrical stimulation of the afferent SLN mimics the effects of laryngeal receptor stimulation by liquids such as water (17), and SLN denervation abolishes the reflex response (1 8).…”