Impaired cardiac function during postnatal hypoxia in rats exposed to nicotine prenatally: implications for perinatal morbidity and mortality, and for sudden infant death syndrome.
Maternal smoking correlates highly with parturitional/neonatal death including SIDS; nicotine exposure of fetal rats reproduces the increased mortality when animals are tested postnatally with hypoxia. In the current study, pregnant rats received nicotine infusions simulating smokers' plasma nicotine levels. At 1-2 days postpartum, the nicotine group displayed normal heart rates, EKG waveforms, and respiratory rates in normoxia. With hypoxia (5% O2, 10 min), controls showed initial tachycardia and a subsequent slight decline in heart rate; atrioventricular conduction was gradually impaired and repolarization abnormalities also appeared. The nicotine group showed no tachycardia and heart rate declined rapidly and precipitously within a few minutes after commencing hypoxia; otherwise, EKG alterations mimicked the controls'. Changes in respiration were identical in the two groups: initial tachypnea and subsequent decline. These results suggest that prenatal nicotine affects sinoatrial reactivity to hypoxia without impairing cardiac conduction per se. These mechanisms explain increased hypoxia-induced mortality in animals exposed to prenatal nicotine, and in man could account for increased morbidity/mortality and SIDS. Our results also indicate the need to test adverse effects of fetal drug exposure using conditions that challenge any given physiological system rather than relying solely on changes under basal conditions.
Slotkin
T A
TA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA. slotk001@acpub.duke.edu
Saleh
J L
JL
McCook
E C
EC
Seidler
F J
FJ
D000818:Animals; D000831:Animals, Newborn; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D007231:Infant, Newborn; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D013398:Sudden Infant Death / Q000209:etiology
D009538:Nicotine