Apr. 6, 2006 Exposure to nicotine the equivalent of smoking two packs of cigarets a day produced complicated, abnormal breathing development during the first 18 days of newborn rats, University of Arizona researchers report.
Ralph Fregosi, presenting the results at three American Physiological Society sessions at Experimental Biology, said his team "found that the required increase in breathing in response to reduced oxygen supply was lower in nicotine-exposed animals compared to the controls over their first nine days. This suggests that prenatal nicotine exposure reduces the ability of a neonatal animal to respond to low blood oxygen, which can lead to prolonged and possibly lethal apneas."
Between nine and 18 days, the situation reversed, and nicotine-exposed rats' response was actually higher than controls, showing an overall complicated, abnormal breathing development over the 18 days.
Cause of apneas still unknown, but ability to restart breathing remains key
Fregosi said his laboratory wants to better understand how smoking during pregnancy disturbs breathing in infants because of increased rates of asthma, sudden infant death syndrome (SIDS), obstructive sleep apnea and impaired arousal responses during sleep. "Our laboratory is particularly interested in the strong association between maternal smoking on the one hand, and the increased incidence of infantile SIDS and obstructive sleep apnea on the other."
In the current study the team studied how prenatal nicotine exposure affected neonate's ability to respond to decreased levels of blood oxygen, and/or low oxygen combined with elevated carbon dioxide. "This is important when the neonate has an 'apnea,' or cessation of breathing, when they are sleeping, because under these conditions the oxygen can be reduced dramatically. Although we still don't understand the cause of the apneas, we know they are frequent, especially in the early neonatal period.
"This is important physiologically, because a reduced ability to respond to low oxygen and/or high carbon dioxide diminishes the ability of the infant to reinitiate breathing and break the apnea. If the apnea becomes prolonged, the oxygen levels in the blood will drop dramatically leading to cardiovascular arrest and death."
Pump implant to simulate prenatal nicotine exposure
The current study exposed animals to nicotine by implanting a small pump loaded with nicotine into pregnant rats, so the neonates were exposed to the nicotine in utero. This mimics the situation observed in a smoking pregnant woman. The dose of nicotine was designed to be equivalent to what the developing fetus would be exposed to if their mother smoked two packs of cigarets a day.
Various levels of oxygen reduction were tested, from 16% to 10% of air (normal air is 21% O2), as well as a 12% oxygen/5% CO2 level.
Developmental switch parallels neurophysiological findings
Fregosi noted that there is "mounting evidence that neurons responsible for controlling their respiratory and cardiovascular systems show a variety of abnormal anatomic and physiologic changes in neonatal animals exposed to nicotine before birth, and the developmental switch between nine and 12 days is consistent with a recent report in the Journal of Applied Physiology on a major readjustment of brainstem neurotransmitter receptor densities near day 12."
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