Josette Khater-Boidin

Central effects of 5-HT on respiratory and hypoglossal activities in the adult cat.

The activities of the diaphragmatic, internal intercostal and hypoglossal-innervated muscles were studied in adult decerebrate cats in response to 5-HT and related agents (8-OH-DPAT and DOI). The drugs were placed on the floor of the IVth ventricle. The mean respiratory frequency (Fi) increased (124-193% of the control value) within 3 min of the 5-HT application, and decreased thereafter (30-90%). The mean Ti and Te changed similarly, but opposite to Fi. With some delay, the hypoglossal-innervated muscles were tonically activated or exhibited increased activities. Methysergide pretreatment completely blocked the effect of 5-HT on all the respiratory parameters and the hypoglossal-innervated muscles activities. The responses to 8-OH-DPAT and DOI indicate that 5-HT modulates the respiratory frequency via activation of both 5-HT1A and 5-HT2 receptors. Nevertheless, the effect of 5-HT on both the expiratory and hypoglossal-innervated muscles seems to depend on 5-HT2 receptors activation only.

Oral stimulations induce apnoea in newborn kittens.

The aim of the present work was to study oral trigeminal mechanisms which might induce apnoeic reflexes in adult cats and kittens at different postnatal ages. Various oral stimulations and electrical stimulations of the lingual nerve produced apnoeas whose duration decreased with age until three weeks of life. In addition, swallowing was only rarely observed before 5 days and then occurred with apnoea until the third week. Responses became similar to those observed in adults between weeks 3 and 4. Thus, in kittens, the nervous control which regulates coordination between breathing and swallowing appears to be immature at birth.

Postnatal development of descending motor pathways studied in man by percutaneous stimulation of the motor cortex and the spinal cord

Using the percutaneous electrical stimulation of the brain and spinal cord, we have determined central motor pathway conduction velocities in a group of 19 healthy fullterm newborns (average post‐conceptional age 39.8 weeks) and in 19 infants between 2 months and 8 years of age. The newborns were examined during the first postnatal week. The percutaneous stimulation of the motor cortex and of the cervical and lumbar enlargements of the spinal cord was made by means of bipolar electrodes. The evoked compound muscle action potentials were recorded by bipolar surface electrodes fixed on the skin overlying the thenar eminence muscles and the tibialis anterior muscle.

Vagal pulmonary afferents and central respiratory effects of 5-HT in newborn rats

In decerebrate newborn rats, serotonin (5‐HT) is a respiratory depressant via activation of 5‐HT2 receptors, whereas it evokes respiratory stimulant effects when applied to the isolated brainstem obtained from the newborn rat. This discrepancy could be due to deafferentation in the in vitro preparation. The aim of our study was to analyse the role of vagal afferents in the modulation of central respiratory effects of 5‐HT. In decerebrate cervically or abdominally bivagotomized newborn rats aged between 0 and 3 days, we recorded electrical activity from the diaphragm and from a hypoglossally innervated tongue muscle, as well as cardiac frequency (Fc), before and after application of 5‐HT to the floor of the IVth ventricle. The effects of related agents (a 5‐HT1A agonist, 8‐OH DPAT, and a 5‐HT2 agonist, DOI) were studied in cervically bivagotomized animals. For comparison, and to assess the spontaneous variability in inspiratory frequency (Fi) and Fc, sham groups were studied. Each group comprised ten newborn rats. In cervically bivagotomized newborn rats, 5‐HT induces a significant increase in Fi, which is the opposite to that observed in decerebrate newborn rats with intact vagi. This respiratory effect is mediated in particular, via activation of 5‐HT1A. By contrast, in abdominally bivagotomized newborn rats, a decrease in Fi was observed in response to 5‐HT (as previously described in decerebrate animals with intact vagi). We conclude that pulmonary vagal afferents modulate the central respiratory action of 5‐HT in decerebrate newborn rats, explaining the conflicting results between in vivo and in vitro experiments.

Nonvagal Reflex Apnea in the Newborn Kitten and during the Early Postnatal Period

The aim of this work was to study the nonvagal mechanisms which might induce apneic reflexes in kittens. Experiments were performed on spontaneously breathing animals (19 kittens at different postnatal ages). Animals were anesthetized (halothane) or decerebrated by transcollicular section of the brainstem. Weakly nociceptive cutaneous stimulations and various oral stimulations were administered in all animals. In 10 kittens, one of the lingual nerves was stimulated electrically. In 3 decerebrate kittens the effects of serotonin on respiratory activity and on muscles innervated by the hypoglossal nerve were studied. All the stimulations produced apneas of variable duration, and expiratory reinforcement was associated with activation of pretracheal muscles. Similar effects were observed after applying serotonin to the floor of the 4th ventricle. Thus serotonin may be involved in the mechanisms that cause some apneas.

Evolution Of Motor, Ia And Cutaneous Nerve-Fibre Conduction Velocities In Premature And Fullterm Newborns

The conduction velocities of motor, IA and non‐nociceptive cutaneous sensory fibres have been studied in the ulnar and median nerves of 145 healthy fullterm neonates and in 77 preterm neonates (postconceptional age‐range 28 to 42 weeks). The posterior tibial‐nerve motor and IA fibres were studied: the sural nerve cutaneous‐fibre conduction velocities were measured in fullterm neonates only. At each age the IA fibre conduction velocities were the highest. There was no difference between the conduction velocity increase per week of postconceptional age in motor and cutaneous fibres. Except for the cutaneous‐nerve fibres, conduction velocities were higher in the upper than in the lower limbs.

The post-potential excitability modulation of α nerve and muscle fibers in human newborn and adult

In order to assess indirectly the excitability of human motor units, the absolute refractory period of the ulnar nerve alpha motor fibers and the absolute irresponsive period of the abductor digiti minimi fibers were measured in 8 premature, 10 fullterm newborns and 10 adults. Results indicate that absolute refractory period of alpha motor nerve fibers appears to be a specific functional property of the membrane, independent of postnatal development. Moreover the maturation of muscle membrane seems slightly delayed in comparison to that of nerve fibers. Indeed the absolute irresponsive period of muscle fibers is slightly higher in premature in comparison with fullterm newborn and adult.

Absolute refractory period of human nerve fibres during postnatal myelination.

In order to study the absolute refractory period of a given group of nerve fibres during development we measured absolute refractory periods and conduction velocities of motor fibres and the most excitable fibres in the human ulnar nerve of newborns, children and adults. In each group of nerve fibres absolute refractory period was not correlated to conduction velocity (i.e. fibre diameters) and was rather constant during development. However, absolute refractory period of the most excitable fibres was smaller than absolute refractory period of motor fibres independently of the subjects age. Thus, it appears that already at birth, absolute refractory period is characteristic for a given group of nerve fibres.

Modulation of the central respiratory effects of 5-HT by vagal afferents in newborn rat.

Recent in vitro studies using brain slices or an isolated preparation of brainstem and spinal cord have confirmed that serotoninergic mechanisms are involved in the central nervous control of breathing. For example, increases in respiratory frequency, via activation of 5-HT1 receptors, have been elicited either by the use of exogenous 5-HT 1 or via the release of endogenous 5-HT after stimulation of the raphe nuclei2. Other workers have reported a biphasic effect of 5-HT on respiratory rate, an initial increase in inspiratory frequency (Fi) being followed by a low-frequency phase despite the continued presence of 5-HT 3,4. Interestingly, the effect of 5-HT on the respiratory rhythm in vitro appears to depend on the baseline respiratory rate4, the inhibitory effect being more pronounced in a preparation with a higher respiratory rate.