Failure to autoresuscitate from apnea by gasping has been suggested to have a role in sudden infant death. Little is known, however, about the factors that influence the ability of gasping to sustain life during acute hypoxia in the newborn. The present experiments were carried out on 105 rat pups to investigate the influence of postnatal age on the time to last gasp during a single hypoxic exposure and on the ability to autoresuscitate from primary apnea during repeated hypoxic exposures. On days 1-2, 5-6, 10-11, 15-16, and 19-20 postpartum, each pup was placed into a temperature-controlled chamber regulated to 37 +/- 1 degrees C and was exposed either to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N(2)-3% CO(2)), and the time to last gasp was determined, or repeated exposure to hypoxia was performed, and the ability to autoresuscitate from primary apnea was determined. Increases in postnatal age decreased the time to last gasp following a single hypoxic exposure and decreased the number of successful autoresuscitations following repeated hypoxic exposures. Thus our data provide evidence that postnatal age influences protective responses that may prevent death during hypoxia as may occur during episodes of prolonged sleep apnea.

Failure to autoresuscitate by hypoxic gasping during prolonged sleep apnea has been suggested to play a role in sudden infant death. Furthermore, maternal smoking has been repeatedly shown to be a risk factor for sudden infant death. The present experiments were carried out on newborn rat pups to investigate the influence of perinatal exposure to nicotine (the primary pharmacological and addictive agent in tobacco) on their time to last gasp during a single hypoxic exposure and on their ability to autoresuscitate during repeated exposure to hypoxia. Pregnant rats received either nicotine (6 mg. kg-1. 24 h-1) or vehicle continuously from day 6 of gestation to days 5 or 6 postpartum via an osmotic minipump. On days 5 or 6 postpartum, pups were exposed either to a single period of hypoxia (97% N2-3% CO2) and their time to last gasp was determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnea was determined. Perinatal exposure to nicotine did not alter the time to last gasp, but it did impair the ability of pups to autoresuscitate from primary apnea. After vehicle, the pups were able to autoresuscitate from 18 +/- 1 (SD) periods of hypoxia, whereas, after nicotine, the pups were able to autoresuscitate from only 12 +/- 2 periods (P < 0.001) of hypoxia. Thus our data provide evidence that perinatal exposure to nicotine impairs the ability of newborn rats to autoresuscitate from primary apnea during repeated exposure to hypoxia, such as may occur during episodes of prolonged sleep apnea.

The purpose of the present study was to investigate the effects of the L-arginine analogue, NG-nitro-L-arginine methyl ester, L-NAME, in modulating renal hemodynamics during postnatal maturation in conscious chronically instrumented lambs. To this end, renal hemodynamic responses to intravenous injection of 10, 20, and 40 mg/kg L-NAME, as well as its inactive enantiomer D-NAME, were measured for 4 h in conscious lambs approximately 1 week (n=10), 3 weeks (n=12), and 6 weeks (n=14) of age. Administration of L-NAME was associated with an increase in renal vascular resistance (RVR) leading to a decrease in renal blood flow. One-week-old lambs were more sensitive to the effects of L-NAME, a marked increase in RVR occurring after the smallest dose administered at 1 week but not at 3 and 6 weeks of age. Renal hemodynamic effects of L-NAME as well as the duration of the responses were also age dependent, such that changes in RVR were greatest and most prolonged in 1-week-old lambs. In addition, a smaller dose of L-NAME was required to attenuate acetylcholine-induced renal vasodilation in lambs aged 1 week compared with older animals. Our data provide new evidence to support the premise that endogenously produced nitric oxide plays a predominant role in regulating renal vascular tone early in life.