Perinatal nicotine exposure impairs ability of newborn rats to autoresuscitate from apnea during hypoxia

Abstract

Failure to autoresuscitate by hypoxic gasping during prolonged sleep apnea has been suggested to play a role in sudden infant death. Furthermore, maternal smoking has been repeatedly shown to be a risk factor for sudden infant death. The present experiments were carried out on newborn rat pups to investigate the influence of perinatal exposure to nicotine (the primary pharmacological and addictive agent in tobacco) on their time to last gasp during a single hypoxic exposure and on their ability to autoresuscitate during repeated exposure to hypoxia. Pregnant rats received either nicotine (6 mg. kg-1. 24 h-1) or vehicle continuously from day 6 of gestation to days 5 or 6 postpartum via an osmotic minipump. On days 5 or 6 postpartum, pups were exposed either to a single period of hypoxia (97% N2-3% CO2) and their time to last gasp was determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnea was determined. Perinatal exposure to nicotine did not alter the time to last gasp, but it did impair the ability of pups to autoresuscitate from primary apnea. After vehicle, the pups were able to autoresuscitate from 18 +/- 1 (SD) periods of hypoxia, whereas, after nicotine, the pups were able to autoresuscitate from only 12 +/- 2 periods (P < 0.001) of hypoxia. Thus our data provide evidence that perinatal exposure to nicotine impairs the ability of newborn rats to autoresuscitate from primary apnea during repeated exposure to hypoxia, such as may occur during episodes of prolonged sleep apnea.

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

“…N lambs had more sighs, and these efforts appeared less efficient in restoring a sustained rise in HR and regular breathing. Sighing and gasping are considered to be key elements in successful cardiorespiratory recovery (27), and our findings of less-efficient sighs support other reports that nicotine exposure impairs the ability to autoresuscitate in situations such as repeated hypoxic exposures or LCR-induced apnea after IL-1B pretreatment (15,28,29).…”

Environmental tobacco smoke and sudden infant death syndrome: a review

“…In support of this theory, a deficiency in adrenomedullary catecholamine release was noted in exposed rat pups experiencing high mortality in the Slotkin et al (1995) study discussed previously. Such alterations in autonomic maturation have also been proposed as explanations in several studies where nicotine administration induced negative effects on hypoxia response (Fewell and Smith, 1998;St.-John and Leiter, 1999;Franco et al, 2000). Furthermore, these effects are seen at relatively low doses of nicotine: Slotkin et al (2002) noted the upregulation of nAChRs in the cerebral cortex and brainstem of monkeys exposed to ETS from mid-gestation (via maternal exposure) into the early neonatal period.…”

“…In neonatal rat pups, Fewell and Smith (1998) investigated the effect of nicotine on time to last gasp during hypoxia exposure (97% N 2 ; 3% CO 2 ), as well as its effect on the ability to auto resuscitate after repeated hypoxia exposure. Administered to pregnant dams by osmotic minipump, nicotine exposures of 6 mg/kg/day began on Day 5 of gestation and continued through Day 5 or 6 postpartum.…”

Sudden Infant Death Syndrome: A Failure of Compensatory Cerebellar Mechanisms?

“…Recent animal evidence demonstrates the importance of adrenal catecholamine release on autoresuscitation from hypoxia, and that prenatal nicotine exposure compromises autoresuscitation, possibly by interference with cardiac conductance changes associated with altered adrenal catecholamine outflow (35)(36)(37). The potential role of loss of protective vagal influences on cardiac conduction disturbances has been outlined earlier (38).…”