Abstract
Failure of gasping to bring about autoresuscitation from hypoxia-induced apnea has been suggested to play a role in sudden unexpected infant death. Little is known, however, about factors that influence the ability of gasping to restore life during severe hypoxia in newborns. Given that adenosine modulates cardiac function during hypoxia-induced apnea and that cardiac dysfunction plays a role in mediating autoresuscitation failure, the present experiments were carried out on 34, 5- to 6-, and 10- to 11-day-old rat pups to investigate their ability to autoresuscitate from hypoxia-induced apnea during repeated exposure to hypoxia after adenosine A1-receptor blockade. Each pup was placed into a temperature-controlled chamber regulated to 37 ± 1°C and repeatedly exposed to an anoxic gas mixture (97% N2 and 3% CO2) until the occurrence of autoresuscitation failure. One group was studied following administration of the selective adenosine A1-receptor antagonist 8-Cyclopentyl-1,3,-dipropylxanthine (DPCPX) and one group was studied following vehicle. DPCPX significantly attenuated bradycardia during hypoxia-induced apnea and impaired the ability of both age groups of pups to autoresuscitate during repeated exposure to hypoxia (5–6 days tolerated – vehicle 17 ± 4 vs. DPCPX 10 ± 2 hypoxia exposures [P < 0.05]; 10–11 days tolerated – vehicle 10 ± 2 vs. DPCPX 7 ± 2 hypoxia exposures [P < 0.05]). Death in all pups resulted from the inability of gasping to restore cardiovascular function during hypoxia-induced apnea although the mechanism of cardiovascular dysfunction/failure was influenced and the occurrence hastened by DPCPX. Thus, our data provide evidence that adenosine acting via adenosine A1-receptors enhances the ability of rat pups to tolerate repeated exposure to severe hypoxia during early postnatal maturation.
Highlights
Newborn mammals are known for their ability to survive a lack of oxygen (Dawes 1968; Adolph 1969)
As previously reported (Fewell et al 2007), DPCPX significantly attenuated the heart rate response recorded during hypoxia-induced primary apnea (Fig. 1); with regard to the heart rate response, there was an effect of age (P < 0.05) and DPCPX (P < 0.05) but not an interaction between these independent variables indicating that the effect of DPCPX was not age dependent
Prior administration of DPCPX diminished the ability of 5–6 day-old and 10–11 day-old pups to survive repeated exposure to hypoxia (Fig. 3); with regard to number of successful autoresuscitations, there was an effect of age (P < 0.05) and DPCPX (P < 0.05) but not an interaction between these independent variables indicating that the effect of DPCPX was not age dependent
Summary
Newborn mammals are known for their ability to survive a lack of oxygen (Dawes 1968; Adolph 1969). When exposed to a period of unrelenting and progressive hypoxia, newborn rats display a characteristic respiratory response that lasts up to 30 min and consists of tachypnea/hyperpnea, primary apnea, gasping, and secondary or terminal apnea (Gozal et al 1996; Fewell et al 2000). After the initial period of tachypnea/hyperpnea, which is mediated by the peripheral chemoreceptors (Lun et al.2015), primary apnea occurs and may be as short as 10 sec in newborn rats or as long as 18 min in newborn ground squirrels (Adolph 1969; Fewell and Smith 1998). Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society
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