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.
ABSTRACT. Experiments were done on five lambs to determine if carotid denervation influences the arousal and cardiopulmonary responses to rapidly developing hypoxemia during sleep. Each lamb was anesthetized and instrumented for recordings of electrocorticogram. electrooculo- The arousal response is an important protective response that may prevent severe hypoxemia and death during sleep (1). Hypoxemia may occur during sleep in individuals with chronic lung disease (e.g. cystic fibrosis [2], bronchopulmonary dysplasia [3], asthma [4]) and/or during central or obstructive apnea. The usual respiratory response to hypoxemia is an increase in ventilation, which tends to increase the alveolar and arterial oxygen tension. However, as the ventilatory response to hypoxemia is decreased during active sleep compared to quiet sleep in lambs (5) and calves (6) during obstructive apnea is usually preceded by arousal (7-lo), the arousal response may be the most important response to hypoxemia during sleep.Previous experiments on young lambs (5, 1 1-13) and calves (6) have demonstrated that arousal occurs from both quiet sleep and active sleep in response to alveolar hypoxia, but the mechanism remains unclear. The purpose of the present experiments was to investigate the effect of carotid-denemation on the arousal response from sleep to rapidly developing hypoxemia in young lambs. MATERIALS AND METHODSFive lambs ranging in age from 1 1 to 24 d were studied. Each lamb was separated from its ewe 3 to 7 d after birth and was housed in our laboratory in a Plexiglas cage with continuous access to milk (Lamb Milk Replacer, Land O'Lakes, Inc., Fort Dodge, IA). The lambs were among other lambs, fed and slept a d libitum, and soon became accustomed to the surroundings and laboratory personnel.Surgical preparation. Each lamb underwent one operation before the study. For surgery, each lamb was given atropine sulfate (0.2 mg/kg subcutaneously); anesthesia was induced by having the lamb breath 3 to 4% halothane in oxygen via a mask. The trachea was then intubated with a cuffed endotracheal tube; anesthesia was maintained by ventilating the lamb's lungs with 0.5-1.0% halothane in oxygen. An ECG, end-tidal carbon dioxide levels, and rectal temperature were monitored during surgery; body temperature was kept near 39°C with a heating pad, and end-tidal carbon dioxide levels were kept near 5% with a volumecycled ventilator.The operation was done when the lambs were between 7 and 2 1 d of age. A double-lumen fiberoptic catheter oximeter (Model U440 Opticath, Oximetrix, Inc., Mountain View, CA; 90% response to a step change in Sa02 within 5 s) was inserted to the thoracic aorta via a femoral artery for continuous measurement of arterial Hb oxygen saturation and blood pressure. Electrodes for the following recordings were also implanted: electrocorticogram (recorded from electrodes placed through burr holes to lie over the parietal cortex), electro-oculogram (recorded from electrodes placed at the inner and outer canthus of the right eye), nuchal...
Experiments were carried out to define the effects of pregnancy on body temperature (Tb) regulation in rats. Tb was measured by biotelemetry in six animals from day 10 of pregnancy (term day 21) to postpartum day 10. Average 24-h Tb decreased from day 15 of gestation to the time of parturition. Furthermore, there was a loss of the normal circadian variation of Tb late in gestation, which was again present by postpartum day 2. The decrease in 24-h Tb on day 15 of gestation resulted from this loss of circadian variation, as Tb did not increase during the dark period. The further decrease in Tb on day 20 of gestation resulted from an overall decrease in Tb during the light and dark periods as well as from a loss of the circadian variation in Tb. Tb increased dramatically within 4 h of birth of the first pup, which always occurred on day 21 during the light period. The mechanisms responsible for these dramatic changes in thermoregulation during late gestation and around the time of parturition are presently unknown.
We studied the effects of infusions (duration 13.4 +/- 2.9 h) of prostaglandins (PG) on fetal breathing movements (FBM) in 12 fetal sheep at 122-141 days gestation. We gave similar doses (1.1 +/- 0.7 microgram . kg-1 . min-1) of PGE2 (8 studies), PGF2 alpha (5 studies), and cyclic endoperoxide analogues (6 studies). During control periods (304 h), incidence of FBM was 41%; this decreased during every infusion. With PGE2, incidence of FBM markedly decreased to 9.8% of control (P less than 0.001). With the other agents the decrease was less profound; incidence of FBM with PGF2 alpha was 63.7% of control and with endoperoxide analogues 69.4% of control (P less than 0.05 for both). During infusions there were no changes in fetal heart rate, arterial blood pressure, pH, or blood gas tensions. In three fetuses (5 infusions) with electrocorticogram recordings, incidence of low-voltage fast activity was unchanged from control values. Inhibition of FBM by PGE2, combined with previous results showing stimulation of FBM by PG synthetase inhibitors, suggests that endogenous PG may inhibit breathing movements in utero and that a change in PG metabolism may contribute to the change in control of breathing at birth.
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