Heart Rate Response to Transient Chemoreceptor Stimulation in Term Infants Is Modified by Exposure to Maternal Smoking

Abstract

Modulation of heart rate (HR) during transient hyperoxia, hypoxia, and hypercapnia was studied in 46 healthy term infants on 103 occasions (postnatal d 2 to 82). Twenty-three infants had smoking mothers (median, 11 cigarettes/d). Transient chemoreceptor stimuli (100% O 2 , 15% O 2 , or 3% CO 2 ) were presented repeatedly during quiet sleep. Beat-by-beat HR and breath-bybreath ventilation were recorded continuously. The coherently averaged HR and ventilation responses to each stimulus were calculated for each infant at each age. Outcome variables (HR change from baseline to end of stimulation, maximum HR change, and time to half-maximum) were analyzed by ANOVA. Overall, HR declined during hyperoxia (median change, 4.2 beats/min) and rose during hypoxia (median change, 4.2 beats/ min) and hypercapnia (median change, 4.6 beats/min). The percentage change in HR was positively correlated with the percentage change in ventilation (p Ͻ 0.001). Increasing number of cigarettes smoked by the mother was correlated with deeper HR declines and smaller HR rises (p ϭ 0.02). For the population as a whole, the HR response lagged 3.8 s behind the ventilatory response during hyperoxia and hypoxia (p Ͻ 0.001), whereas during hypercapnia there was no significant lag. The lag in HR response in the smoke-exposed group was 2.5 s greater than that in the control group for all three stimuli (p ϭ 0.001), and the difference increased with the number of cigarettes smoked by the mother (p Ͻ 0.01). Both pulmonary reflexes and the type of the chemoreceptor stimulus seemed to influence HR. In fetal life, peripheral chemoreceptor stimulation by hypoxia or hypercapnia produces bradycardia and peripheral vasoconstriction (1, 2). After birth, however, the same stimuli cause hyperventilation, tachycardia, and peripheral vasodilation (3-5). These responses are thought to result from an interaction of reflexes. The primary cardiac effect of chemoreceptor stimulation is bradycardia, mediated via the vagal innervation of the heart. However, a concomitant increase in V E will increase lung stretch receptor activity, give slight hypocapnia, and affect central respiratory neurons, and these responses together cause an overriding tachycardia. This interaction has been described in a number of species, including primates (4 -8).In anesthetized animals, elaborate experiments can be performed in which marked changes in arterial O 2 and CO 2 content are introduced or the peripheral chemoreceptors are stimulated chemically or electrically. Cardiovascular effects may then be assessed while V E is kept constant, the degree of lung inflation is controlled, or pulmonary afferent nerves are cut or pharmacologically blocked. It is not possible to achieve a similar level of control in noninvasive studies in humans. However, trained subjects can voluntarily keep their V E constant, and in some pathologic conditions breathing movements are temporarily absent. Experiments making use of these phenomena have given more indirect indications of an interaction between the effe...

Development of Ventilatory Response to Transient Hypercapnia and Hypercapnic Hypoxia in Term Infants

“…The averaged ventilatory responses were analyzed in a virtual instrument programmed in LabVIEW 5.0 (National Instruments Corp., Austin, TX, U.S.A.), as described previously (24). For illustration purposes, the coherently averaged V E, VT, and f R response of the entire group was also calculated for each stimulus-age combination ( Figs.…”

Differential Control of Central Cardiorespiratory Interactions by Hypercapnia and the Effect of Prenatal Nicotine

“…Rats exposed to nicotine prenatally have a lower basal heart rate than unexposed animals (Fewell et al, 2001), and neonatal rats exposed to nicotine in utero show reduced tolerance for hypoxia caused by impaired heart rate control (Slotkin et al, 1997). Furthermore, human infants of smoking mothers also exhibit exaggerated heart rate responses to hypoxia (Sovik et al, 2001). …”

Heart rate variability in preterm infants and maternal smoking during pregnancy

“…Moreover, we have seen that infants of smoking mothers have an altered sympathovagal modulation of the cardiovascular system [1,11]. In full-term newborns, the smaller heart rate increase during hypoxia was correlated with the increasing number of cigarettes smoked by the mother [34]. In rats, prenatal nicotine suppressed the tachycardia caused by sinoatrial reactivity to hypoxia and within a few minutes of hypoxia, the heart rate declined rapidly and precipitously [33].…”

“…The number of cigarettes smoked was correlated with deeper infant heart rate decline during hyperoxia and smaller heart rate rises during hypoxia and hypercapnia [34]. Browne et al studied the blood pressure responses to tilting at 2-3 days and 3 months of age in infants from smoking and non-smoking mothers [1].…”