Gestational cigarette smoke exposure and hyperthermic enhancement of laryngeal chemoreflex in rat pups

Abstract

Laryngeal chemoreflex (LCR) apnea occurs in infant mammals of many species in response to water or other liquids in the laryngeal lumen. The apnea can last for many seconds, sometimes leading to dangerous hypoxemia, and has therefore been considered as a possible mechanism in the Sudden Infant Death Syndrome (SIDS). We have found recently that this reflex is markedly prolonged in decerebrate piglets and anesthetized rat pups that are warmed 1–3 °C above their normal body temperatures. We intermittently exposed pregnant rats to cigarette smoke and examined the LCR in their four- to fifteen-day-old offspring under general anesthesia, with and without whole body warming. During warming, pups of gestationally smoke-exposed dams had significantly longer LCR-induced respiratory disruption than similarly warmed control pups. The results may be significant for the pathogenesis and/or prevention of SIDS as maternal cigarette smoking during human pregnancy and heat stress in infants are known risk factors for SIDS.

Activation of serotonergic neurons in the medullary caudal raphe shortens the laryngeal chemoreflex in anaesthetized neonatal rats

“…Among these risk factors are maternal cigarette smoke exposure (Xia et al . ), specifically intrauterine nicotine exposure through the mother (Xia et al . ), and these environmental exposures sensitize the LCR and exaggerate thermal prolongation of the LCR, which may be associated with thermal stress (Curran et al .…”

“…; Xia et al . , , , ). Many investigators have suggested that the LCR is the first step in a process that starts with respiratory inhibition and apnoea and ends with failed termination of apnoea, failed restoration of regular breathing and failed arousal, leading to sudden infant death syndrome (SIDS) and asphyxial deaths in human infants (Downing & Lee, ; Page & Jeffery, ; Thach, ).…”

“…Previously, we investigated the first part of this hypothesis, identifying risk factors for SIDS that increase the sensitivity and strength of the LCR (Xia et al . , , , ). More recently, we turned our attention to the second part of the hypothesis.…”

Sudden Unexpected Death in Fetal Life Through Early Childhood

“…95 The effects of 5-HT deficiency in these models on the laryngeal chemoreflex is under investigation. 96 Physiologic effects also have been shown to be exacerbated by the risk factors of prenatal exposure to alcohol at a critical postnatal age, 97 cigarette smoke/nicotine, 98,99 hyperthermia, 100 and other epigenetic factors (S. Lee, E.E. Nattie, A. Li, unpublished data).…”

TRPV1 channels in the nucleus of the solitary tract mediate thermal prolongation of the LCR in decerebrate piglets

“…Reduced pH - for example during hypercapnia, bradykinin - perhaps related to coexisting infection or inflammation, and nicotine appear to enhance TRPV1 sensitivity (Venkatachalam and Montell, 2007). Interestingly, the thermal prolongation of the LCR is enhanced in neonatal rats born to mothers exposed to tobacco smoke or nicotine during pregnancy (Xia et al, 2009; Xia et al, 2010). Finally, serotonergic activation of neurons may enhance TRPV1-dependent neurotransmitter release (Ohta et al, 2006; Suguira et al, 2004); a finding of interest in view of the evidence that brainstem serotonergic function may be altered in many infants who died of SIDS (Paterson et al, 2006) For all these reasons, we were interested in testing the hypothesis that TRPV1 receptors mediate the thermal prolongation of the LCR originating in the NTS.…”