SIDS Linked With Loss of Hypoxic Sensitivity in Chromaffin Cells

The association between maternal smoking, or exposure to smoke, and sudden infant death syndrome (SIDS) appears to be the result of nicotine exposure, which impairs chromaffin cells' ability to detect and respond to oxygen deprivation, the results of an animal study suggest. Specifically, nicotine exposure impairs the ability of adrenal chromaffin cells to release catecholamine in response to oxygen deprivation, researchers report in the Federation of American Societies for Experimental Biology (FASEB) Journal.

"Nicotine in cigarette smoke has been linked to several deleterious side effects on the offspring of smoking mothers, including impaired development of the sympathoadrenal system, abnormal arousal reflexes, and SIDS," according to principal investigator Dr. Colin A. Nurse and colleagues from McMaster University, Hamilton, Ontario.

Normally, catecholamine is released from adrenomedullary chromaffin cells in response to stressors, such as hypoxia and hypercapnia, Dr. Nurse's group explains, a mechanism that is critical for the infant to adapt to life outside of the womb.

The team used several approaches to assess chromaffin cell response to hypoxia or hypercapnia in the neonatal rat. Dams were randomly assigned to receive either saline (control) or nicotine bitartrate 14 days before mating and during pregnancy. Dams delivered naturally and the team collected the pups immediately after birth.

Typical responses to hypoxia and hypercapnia were observed in adrenomedullary chromaffin cells isolated from the pups born to dams treated with saline. In contrast, adrenomedullary chromaffin cells from pups born to dams treated with nicotine exhibited a marked suppression or loss of hypoxic sensitivity. Hypercapnic sensitivity and the expression of carbon dioxide markers appeared normal in nicotine-treated cells.

"We found that when neonatal chromaffin cells were cultured in the presence of chronic nicotine base at substrating doses...for approximately 1 week, they lost hypoxic sensitivity, in contrast to control cultures grown without nicotine base," Dr. Nurse and colleagues report.

However, they also found that exposing these cells to mecamylamine, a nicotine blocker, prevented the loss of hypoxic sensitivity, despite nicotine exposure.

FASEB J 2008;22.

Reviewed by Ramaz Mitaishvili, MD

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