Effects of Chronic Hypoxia on Chemoreceptor Function in the Newborn

Abstract

In the adult, hypoxia produces a sustained increase in minute ventilation although in the fetus it inhibits fetal breathing movements. In the newborn, hypoxia produces a characteristic ‘biphasic’ respiratory response: minute ventilation increases in the first 1–2 mins of hypoxia but then falls towards control over the next 5 mins. The initial increase in minute ventilation (Phase 1) is due to stimulation of the peripheral chemoreceptors, this stimulation being maintained throughout the hypoxia. The secondary fall in minute ventilation is thought to be due to the operation of some central nervous inhibitory process which reduces minute ventilation (Blanco et al 1984a, Lawson and Long 1983). Thus the response consists of two components: a peripheral chemoreceptor-mediated stimulation of minute ventilation and a central inhibitory component. A balance exists between these two components, this balance being tipped towards the peripheral chemoreceptor stimulatory mechanism in the adult. In the neonate, the mechanism which predominates depends on the duration of exposure to, and the intensity of, hypoxia. Recently, we have studied the relative rates of maturation of these components in newborn rats (Eden and Hanson 1985). Respiratory disorders of the newborn are often associated with chronic hypoxaemia. In the rat chronic hypoxia from birth alters the respiratory response to episodes of acute hypoxia, by abolishing the initial increase in minute ventilation (Eden and Hanson 1985). This effect could be either by delaying or reducing postnatal chemoreceptor resetting (Blanco et al 1984b) or by altering maturation of the central inhibitory process. Almitrine bismesylate (S2620, Servier) is a drug which is a specific stimulant of the arterial chemoreceptors (Bisgard, 1981). It has been shown to reduce the secondary fall in minute ventilation in acute hypoxia in conscious newborn kittens (McCooke and Hanson 1985). We wondered if administration of almitrine to chronically hypoxic newborn rats would redress the balance and permit an increase in minute ventilation to occur on exposure to acute hypoxia.