Hypoxia and auto resuscitation in the neonatal rodent with special reference to the sympatho-adrenal system

Abstract

Preterm infants exhibit irregular breathing with frequent episodes of apnea, which may be associated with cyanosis and bradycardia. Perinatal asphyxia causes a considerable amount of morbidity and mortality that occurs during early life. Studies of mechanisms responsible for perinatal asphyxia are therefore very important. The main purpose of tile present study has been to investigate physiological mechanisms during perinatal asphyxia with special emphasis on respiration.

Anaesthetized newborn guinea pigs responded to hypoxia with a biphasic response in ventilation, i.e., an initial increase followed by a decrease. Cerebral activity was depressed during hypoxia. Regression analysis showed a liner correlation between ventilation and cerebral activity during hypoxia. Apnea occurred in some cases prior to the depression of CFM activity, indicating that central control of respiration off switch mechanism is activated during severe asphyxia.

During acute anoxia (100% N2), animals responded with hyperpnea, primary apnea, hypoxic gasping and secondary apnea. One-day-old rats tolerated anoxia much longer than 8- day-old. Adrenalectomy reduced the ability to tolerate anoxia and autoresuscitation. This effect was also seen after pretreatment with the [alpha]-receptor antagonist phentolamine, while the ß-receptor antagonist propranolol did not show such effect. It seems that intact adrenal function is important in maintaining proper duration of gasping during anoxia and for autoreSUSCitation from anoxia during early postnatal life. This underlying mechanism appears to involve [alpha]-adrenergic receptors.

Supplementation with glucose prolonged the anoxic tolerance. However, hyperglycaemia resulted in a reduced autoresuscitation. The difference in survival rate seemed not to be attributed to accumulation of lactate in the blood.

Labetalol and prazosin prolonged the gasping period during anoxia, but lowered survival rate in the 8-day-old rats. Labetalol significantly decreased BP and HR, while prazosin showed a tendency towards hypotension. Autoresuscitation failed in the presence of anesthesia indicating that general cerebral depression might abolish this mechanism. These effects may involve [alpha]1-adrenergic receptor blockade. Since labetalol is used in the clinic for the management of pregnancy- induced hypertension these results may imply a potential risk of a failure of autoresuscitation in the presence of perinatal asphyxia probably due to the blockade of the life saving mechanisms evoked by catecholamines.

Severe asphyxia is often associated with hypoxic ischemic encephalopathy. Brain damage developed after hypoxia-ischemia. Post-hypoxic treatment with clonidine protected the neonatal brain from damage by 45%, while labetalol, prazosin and idazoxan had no such effect.