Altered Breathing Pattern and Tachycardia in Young Lambs Exposed To Nicotine Prenatally

Abstract □ 121

Maternal smoking during pregnancy may result in multiple severe consequences for the young child, e.g., obstructive lung and increased risk for the sudden infant death syndrome. The responsible ingredients in tobacco smoke for these effects are not known. We have investigated effects of prenatal nicotine exposure in young lambs and have previously reported that prenatal nicotine exposure attenuates oxygen sensitivity, delays hypoxic arousal and impairs the cardiorespiratory response to acute hypoxemia in sleeping young lambs (Pediatr Res 41:302A, 1997). Studies with dopamine receptor blockers indicated that these effects were, in part, mediated by dopaminergic modulation of the peripheral chemoreceptors (Pediatr Res 43:332A, 1998). In addition, we have observed an altered breathing patterns in these prenatally nicotine exposed young lambs, which point to alterations in mechanical properties of the respiratory system.

Subjects & Methods: Seven pregnant ewes were infused continuously with nicotine, 40mg/d during the last trimester. Seven lambs exposed to nicotine before birth only (N) and 7 control lambs (C) were studied during quiet sleep at an age of 3 - 9 d with a breath-by-breath method (Eur J Appl Physiol 74:44,1996) for determination of minute ventilation (V_I), tidal volume (V_T), respiratory rate (RR), inspiratory/total breath time (T_I/T_T), airway occlusion pressure (P_0.1), mean inspiratory flow (V_T/T_I), end tidal P_CO2 (PET_CO2), effective impedance (P_0.1/V_T/T_I), heart rate (HR) and blood pressure (BP).

Results: Plasma nicotine concentration in the ewes was 7±1 ng/ml (mean ± SD) and the nicotine metabolite cotinine was 18±5 ng/ml. HR was significantly increased in N: 241±22 bpm compared with C: 185±19 bpm (p<0.001, t test). BP was not significantly different, N: 86±13 mmHg, C: 92±10 mmHg. Ventilatory parameters are presented in the table.

Table 1

Summary: The higher heart rate in the nicotine exposed lambs suggests an increased resting sympathetic tone. Compared with control lambs, nicotine exposed lambs were breathing faster with reduced tidal volume and increased inspiratory drive (P_0.1). Effective impedance was higher in the nicotine exposed lambs which might reflect decreased compliance and/or increased airway resistance. The markedly altered breathing pattern suggests that prenatal exposure to a low concentration of nicotine results in abnormal development and postnatal function.

Conclusion: The combined effects of altered control of breathing and decreased lung function may predispose both to SIDS in infancy and obstructive lung disease later in childhood (HD 28916)