Effects of Hyperglycemia on Gasping and Autoresuscitation in Newborn Rats

Abstract

The aim of this study was to test the effects of glucose on the gasping ability and survival in a rat pup model during acute anoxia. Newborn rat pups of both 1 and 8 days of age were given glucose (30 and 60 mg/animal) or saline intraperitoneally and subsequently subjected to anoxia (100% N₂). Glucose supplement induced hyperglycemia. Respiration was recorded by barometric plethysmography. The rat pups responded to acute anoxia with a robust sequence of respiratory pattern: hyperpnea, primary apnea, hypoxic gasping and secondary apnea. During anoxia the 1-day-old rats gasped much longer than the 8-day-old rats (23.4 ± 1.0 vs. 6.1 ± 0.5 min, p < 0.001). No difference was found in gasping duration between the saline control and the glucose-supplemented 1-day-old rat pups. The 8-day-old supplemented rats gasped much longer (9.3 ± 0.5 min) than the control rats (6.1 ± 0.5 min, p < 0.01). The animals autoresuscitated when they received oxygen (100%) during the gasping period. When oxygen was given after the gasping period, the survival rate was 33.3% in control and 0% in supplemented 1-day-old rats, and 100% in control and 50% in glucose-supplemented 8-day-old rats (p < 0.02). Further controlled experiments for a fixed period of anoxia to 13.5 min resulted in survival rates of 50.0% for controls and 28.6% for supplemented animals, respectively. The overall survival rate was then 85.2% in control and 52.9% in supplemented 8-day-old rats (p < 0.05). Lactate concentration in blood rapidly increased in the first 6 min of anoxia and thereafter gradually increased to 22.1 mmol/l around the last gasp in the 1-day-old rats. Hyperglycemia did not cause further accumulation of lactate despite a transient elevation over the control rats at 6 min of anoxia. In the 8-day-old supplemented animals the lactate level was only modestly increased, probably due to the prolonged gasping period. In conclusion, we found that gasping performance was well preserved in the 8-day-old glucose-supplemented rats, whereas the autoresuscitation mechanism after the last gasp might be altered due to hyperglycemia. In addition, the accumulation of lactate in the blood did not affect the gasping performance and the mechanisms of autoresuscitation.

Postnatal age influences the ability of rats to autoresuscitate from hypoxic-induced apnea

“…Therefore, our current experiments were carried out at thermoneutrality to minimize deviations in basal core temperature from normal in this altricial species, which has a limited ability to regulate its core temperature when exposed to ambient temperatures outside its thermoneutral zone (29,33). On exposure to a single period of hypoxia, our rat pups exhibited a triphasic gasping pattern following primary apnea as has been previously shown to occur by others in newborn rats (21,44) and rabbits (6, 28) but not in mice (25). This triphasic gasping pattern consisted of an initial phase of rapid gasping (phase I) that was followed by a second phase of slower gasping (phase II); finally there was a third phase of rapid gasping (phase III), which eventually waned and gave way to terminal or secondary apnea and death.…”

Prior exposure to hypoxic-induced apnea impairs protective responses of newborn rats in an exposure-dependent fashion: influence of normoxic recovery time

“…In our experience, gasping occurs within 60 -90 s of the onset of hypoxia, and naive 5-to 6-day-old rat pups may gasp up to 15 min and exhibit as many as 86 potential autoresuscitation producing gasps. Our laboratory and others have shown that one or more of the previously mentioned gasping characteristics are modulated in this age range of rat pups by factors such core temperature (28), glucose (44), catecholamines (45), nitric oxide (13), and glutamate (12). Given that all of these factors may be altered in one way or the other by exposure to hypoxia, our present experiments have been carried out to determine whether prior exposure to hypoxic-induced apnea, such as may occur during prolonged obstructive apnea or positional asphyxia, influences gasping on exposure to unrelenting hypoxia.…”

“…Although the mechanism of the altered gasping pattern after prior exposure to hypoxic-induced apnea is unknown, it may have resulted from substrate depletion, altered neuroendocrine function, or synthesis and release of neuromodulators that influence hypoxic gasping. As previously mentioned, a number of factors have been shown to govern the time to last gasp in rats during early postnatal development on exposure to unrelenting hypoxia including core temperature (28), glucose (37,44), catecholamines (45), excitatory amino acids (12), and nitric oxide (13). Our laboratory has previously shown that exposure to hypoxia induces a "regulated" decrease in core temperature (3) and that core temperature influences the time to last gasp as well as the total number of gasps in 5-to 6-day-old rat pups on exposure to unrelenting hypoxia.…”

Gasping and autoresuscitation in the developing rat: effect of antecedent intermittent hypoxia

“…Similarly, depletion of cardiac glycogen with recurrent autoresuscitations was advanced as one of the mechanisms potentially leading to autoresuscitation failure in the usually successful autoresuscitating BALB/c mice (3). However, external fuel delivery as brought about by glucose supplementation before the asphyxic exposure exerts divergent effects on gasping and autoresuscitation (28). Indeed, Yuan and colleagues (28) have shown that hyperglycemia will prolong the overall duration of gasping but reduce the frequency of autoresuscitation.…”

“…However, external fuel delivery as brought about by glucose supplementation before the asphyxic exposure exerts divergent effects on gasping and autoresuscitation (28). Indeed, Yuan and colleagues (28) have shown that hyperglycemia will prolong the overall duration of gasping but reduce the frequency of autoresuscitation. Yuan et al (29) also examined the role of adrenergic receptors, and found that adrenalectomy shortened gasping duration in both 1-day-old and 8-day-old rats, whereas the nonselective ␣-receptor antagonist phentolamine reduced the duration of gasping in 1-day-old rats but prolonged this duration in 8-day-old rats, with similar effects on gasping by the nonselective ␤-receptor antagonist propranolol.…”