Comparison between hypothermia and glutamate antagonism treatments on the immediate outcome of perinatal asphyxia

Abstract

This study investigated the influence of temperature or glutamate antagonism on the immediate outcome of perinatal asphyxia. Perinatal asphyxia was produced by water immersion of fetus-containing uterus horns removed by cesarean section from ready to deliver rats. The uterus horns were kept in a water bath for different time periods, before the pups were delivered and stimulated to breathe. After delivery, the pups were assessed for behavior and for systemic glutamate, aspartate, lactate and pyruvate levels measured with in vivo microdialysis, or ex vivo for energy-rich phosphates, including adenosine triphosphate (ATP), in brain, heart and kidney. In a series of experiments, asphyxia was initiated in a water bath at 37 degrees C, before the pup-containing uterus horns were moved for different time intervals to a 15 degrees C bath. In another series of experiments, the mothers were treated with N-methyl-D-aspartate (NMDA) antagonist, dizocilpine (MK-801), or alpha-amino-3-hydroxy-methylisoxazole-4-propionic acid (AMPA) antagonist,2,3-dihydroxy-6-nitro-7-sulfamoyl benzo(f) quinoxalin NBQX) 1 h before hysterectomy and asphyxia at 37 degrees C. The rate of survival rapidly decreased following exposure to more than 16 min of asphyxia, and no survival could be observed after 22 min of asphyxia. An LD50 was estimated to occur at approximately 19 min of asphyxia. The outcome was paralleled by a decrease in ATP in kidney, followed by a decrease in heart and brain. A maximal decrease in ATP was observed after 20 min of asphyxia in all tissues. Systemic microdialysis revealed that glutamate, aspartate and pyruvate levels were increased with a peak after 5 min of asphyxia. In contrast, lactate levels increased along with the length of the insult. Survival was increased when the pup-containing uterus horns were moved from a 37 degrees C to a 15 degrees C bath, at 15 min of asphyxia (the LD50 was thus increased to 30 min). If the shift occurred at 10 or 5 min of asphyxia, the LD50 increased to 80 or 110 min, respectively. The effect of glutamate antagonism was minor compared to hypothermia; the best effect (an increase in the LD50 to approximately 22 min) was observed after combining AMPA and NMDA antagonists.

The influence of EPO and hypothermia on the kidneys of rats after perinatal asphyxia

“…Hypothermia as a therapeutic measure is most widely used after ischemia/ hypoxia of the central nervous system. In this context, it is important to determine the effect of hypothermia on other organs, including kidneys [12,22,24]. Several published studies have addressed the effects of deep hypothermia and its application for the preservation of kidney function for transplantation.…”

“…The incidence of asphyxia is around 1-1.5% and varies between different subgroups of neonates depending on birth weight and gestational age. The most common conditions that cause prenatal hypoxia are placental dysfunction and prolonged labor [12,16].…”

“…The experimental model of perinatal asphyxia that was used for this experiment has already been described in similar studies [12,13].…”

Pharmacological Treatment of Hypoxic-Ischemic Reperfusion Injury of the Newborn Brain in the Clinical Setting: What are the Possibilities in the Near Future?

“…Moderate hypothermia has been tested in various animal [59,60,61,62] and human studies [6,63,64,65,66,67,68,69]. It is thought that moderate hypothermia prevents brain damage by reduction of caspase activity [59], glutamateincrease and free radical formation [5,62].…”

Correlation of blood gas status with the mortality of neonates admitted in ICU

“…Immediately after birth asphyxia, hypothermia generally lower metabolic rates and diminishes the glutamate levels in brain. [12][13] In neonatal sepsis, unstable temperature and less tissue perfusion leading to derangement of acid-base balance. Hence, it is desirable to have values corrected for patient temperature.…”