Nicotine Attenuates the Ventilatory Response to Hypoxia in the Developing Lamb

Abstract

Decreased ability to generate a hyperventilatory response to hypoxemia is believed to be an important mechanism in the pathophysiology of sudden infant death syndrome, and maternal smoking is a leading risk factor. To investigate whether there may be a link between these two observations, we studied five Iambs at mean ages of 7, 17, and 27 d to determine the effects of an i.v, infusion of nicotine (0.5 j.Lg/kglmin) on ventilation when peripheral chemoreceptor activity was stimulated by hypoxia (0.1 Fi0 2 ) or briefly inhibited by hyperoxia. Ventilatory measurements were performed using a computer-aided occlusion valve device which permitted breath-by-breath determinations of inspiratory occlusion pressures (P0.1) and minute ventilation. Nicotine attenuated the early ventilatory response to hypoxia (min 1, 2, and 3 of the test) by 8, 26, and 37%, respectively, at the age of 7 d (analysis of variance overall, p < 0.05), by 23%, 23 and 37% at 17 d (p = NS) and by 40,45, and 37% at 27 d (p < 0.05). The decrease in ventilation in response to hyperoxia during the control study without nicotine was 18,35, and 34% at 7, 17, and 27 d, respectively. Nicotine caused a greater decrease in the response: 31, 45, and 46%, respectively, (p < 0.05 at 27 d). The paradoxical effects of nicotine, attenuation of the ventilatory response to hypoxia and augmentation of the response to A substantial number of infants who die of SIDS have been reported to have brain stem gliosis (1) and elevated hypoxanthine level s in the vitreous humor (2) , findings suggestive of repeated hypoxemic epi sodes before death. These ob servations, together with reports of altered neurotransmitter content

Adverse Effects of Nicotine and Interleukin-1β on Autoresuscitation After Apnea in Piglets: Implications for Sudden Infant Death Syndrome

“…In contrast, lambs subjected to acute infusion of nicotine had decreased ventilation during hypoxia. 30 This might indicate that postnatal exposure to nicotine has more effects on respiration during hypoxia than prenatal exposure, but how the combined effects of prenatal and postnatal exposure to tobacco constituents affect respiration has not been explored. None of these studies addressed the effects on apnea, whereas results in our study should be related both to the hypoxic event and the apnoeic reflex and autoresuscitation in the piglet sedated by azaperone.…”

“…NIC ϩ IL-1␤ had significantly more spontaneous apneas the last 5 minutes before induction of apnea (2 [.3-3] vs 0 [0 -0]; P Ͻ .03; Fig 2). Apneas were prolonged (46 seconds [39 -51] vs 26 seconds [22][23][24][25][26][27][28][29][30][31]; P Ͻ .01; Fig 2) with greater fall in Sao 2 (Fig 3), and followed by far more spontaneous apneas the following 5 minutes (6.6 [4.0 -7.9 Fig 3). These prolonged adverse effects on ventilation were reflected in lowered Pao 2 , elevated Paco 2 and lowered pH 2, and even 5, minutes after induction of apnea (all P Ͻ .04; Table 2).…”

Impaired Cardiorespiratory Recovery after Laryngeal Stimulation in Nicotine-Exposed Young Lambs

“…The lambs were instrumented with placement of a tracheal window and arterial and venous catheters at the age of 1-3 d (7,8). When not studied, tracheal patency was reestablished with a piece of endotracheal tube (Portex, Keene, NH, U.S.A.).…”

“…The clinical importance of these escape and defense mechanisms are supported by observations that infants who are at risk for life-threatening events are also less able to recover from LCR-induced reflex apnea and bradycardia (5,6) In this study, we tested the hypothesis that long-term postnatal exposure to nicotine attenuates and prolongs recovery from apnea and bradycardia in response to LCR stimulation. This notion was based on our previous observations that postnatal nicotine exposure leads to an attenuation of cardiorespiratory defense mechanisms to hypoxia (7). We therefore assumed that nicotine, which has effects on both sympathetic regulation and the ventilatory response to hypoxia, could adversely affect cardiorespiratory recovery from induced apnea.…”

“…We used chronically instrumented, unanesthetized lambs, an animal model used in our laboratory in a number of studies addressing the mechanisms of hypoxic defense, LCR response, and effects of nicotine (7)(8)(9).…”