Descripción detallada de métodos por objetivos específicos

The relative ease with which a HBIR response may be elicited in newborn infants suggests that feedback from mechano-receptors has a more pronounced effect on the central respiratory control system in immature animals, and plays an important role in determining expiratory time during early postnatal life (Trippenbach, 1994). For newborn infants, respiratory timing is crucially important in maintaining a dynamically elevated lung volume (Kosch and Stark, 1984; Rantjen et al, 1989). One effect o f the highly compliant chest wall during early infancy is relatively inefficient ventilation due to paradoxical breathing movements and altered inspiratory air flow (Feldman et al, 1990; Papastamelos et al, 1995). The transition from the infant breathing pattern o f a dynamically elevated FRC to the adult strategy o f a passively determined FRC, is thought to occur in the second half o f the first year o f life (Colin

et al, 1989). To this end, infants may rely strongly on the physiological role o f the HBIR in regulating respiratory rate and depth, in order to minimise alveolar collapse until the chest wall stiffens with maturity (Kosch and Stark, 1984; Colin et al, 1989).

Resting lung volume, which provides an essential reservoir o f oxygen supply, is inherently unstable in newbom infants, due to their highly compliant chest walls (Papastamelos et al, 1995). During the first weeks o f life, infants use their respiratory muscles, including those of the upper airways, to brake expiratory flow, delay lung emptying, and hence maintain a dynamically elevated lung volume (Stark et al, 1987). It has recently been shown that this pattern of breathing diminishes during the first six weeks of life irrespective of gestational age (Stocks et al, 1994a). Consequently, at term equivalent, despite having similar respiratory system compliance, expiratory braking of airflow is less marked in preterm than term infants. Under these circumstances, an increased respiratory rate, mediated by vagal stimulation in response to low lung volumes, may provide the most effective breathing strategy until the mechanical properties of the lung and chest wall have stabilised.

A similar rise in respiratory rate and HBIR activity during the early postnatal period has been observed in newbom rats (Matsuoka and Mortola, 1995), as in the current

investigation. It has also been shown that while hypoxia and/or hypercapnia attenuate the HBIR in more mature animals, these chemical stimuli have minimal influence shortly after birth (Matsuoka and Mortola, 1995). Furthermore, in infants, hypoxic- induced bradycardia usually only occurs during apnoea, since input from the pulmonary stretch receptors attenuates or reverses this mechanism (Gaultier, 1995; Wennergren et al, 1993). However, despite the increased level of HBIR activity observed in newborns, the vagus nerve appears relatively immature at birth, with fewer myelinated fibres, a lower discharge frequency and a smaller percentage o f active slowly adapting pulmonary stretch receptors than in adults o f the same species (Fedorko et al, 1988). This may reflect increased sensitivity of stretch receptors during early development or more inhibition of higher cortical control. Age-related changes in chemosensitivity may increase the sensitivity of the respiratory control centre to stretch receptor input during early life, thereby providing an increased respiratory drive during a critical period o f extra-uterine adaptation. Alternatively, dynamic elevation o f end-expiratory lung volume and enhanced activity of upper airway receptors during occlusion may potentiate the vagal afferent stimulus in infants, as has been reported to occur in lambs (Webb et al,

1994).

Although neither the pathophysiology nor aetiology of SIDS is well understood, it is probable that death is related to the failure o f respiratory regulatory mechanisms that ultimately lead to insufficient respiratory drive (Davies and Gantley, 1994). A vagal afferent input is essential for maintaining adequate respiratory drive in newbom animals, in whom vagotomy results in respiratory failure and death. As the mechanical aspects of breathing change with development, presumably so do the central control mechanisms (Feldman et al, 1990), and deviations from the normal development process may result in dysfunction in the response to challenges such as hypoxia.

The findings o f this study suggest that important transitions in respiratory control processes occur between 12 to 15 weeks PNA in fullterm infants, and that these changes are delayed in preterm infants. While the functional importance o f the reduction o f the reflex activity is not clear cut, the findings o f this study indicate that onset of this diminution coincides with the peak incidence of SIDS. Fleming et al

(1988b) have indicated that maximum instability of respiratory control occurs at a similar age. Although the contribution o f sub-clinical changes in vagally-mediated respiratory control processes is unclear, the persistence of a strong HBIR and increased RR for a longer postnatal period in preterm infants suggests a developmental delay in autonomic control following preterm delivery.

During the vulnerable period when infants are at greatest risk o f SIDS, i.e. between 2 and 6 months o f age, there appears to be an instability in the regulation o f breathing as cortical brain mechanisms begin to dominate over earlier brain stem systems, replacing a primitive and relatively inflexible system with one in which some learning is required for its evolution (McKenna, 1986). McKenna (1986) postulated that the complexity and extensiveness o f the developing intercommunication between the cortex and the brain stem, that enable the changes necessary for infants’ voluntary respiratory behaviour when they cry and emit non-crying vocalizations, put them in greater respiratory jeopardy than non-verbal species. In McKenna’s view (1986), the purpose o f manipulations of airflow exhibited during crying behaviour at an early age, appears to be practice for speech breathing which begins at approximately 7 months of age. The findings of the current investigation may thus indicate the onset o f increased stability and control o f breathing by higher respiratory centres during early infancy.

With the rapid increase in the number o f alveoli with increasing age, the lungs grow (Hislop, 1995) and the chest wall stiffens gradually between infancy and early childhood (Papastamelos et al, 1995; Colin et al, 1989). The stiffening of the chest wall may coincide with the development o f various motor acts which require some degree o f ribcage stability, but are themselves not involved in breathing, e.g. the development o f speech, rolling over and sitting up. As each behaviour involves co­ ordination of respiratory muscles, it is plausible that the development o f these behavioural activities also involves the co-ordination o f the higher respiratory centres. The decline in HBIR activity during early infancy may also reflect concurrent changes in other respiratory control mechanisms, such as changes in the development o f thermoregulation (Andrews et al, 1991; Fleming et al, 1988a), sleep state (Bonora and Boulé, 1994), and peripheral chemoreflex responses (Blanco, 1994).

Prematurity is associated with a 2-4 fold increase in the relative risk of SIDS (Golding

et al, 1985) and has been noted to be an independent risk factor for infants dying beyond 24 weeks o f postnatal age (Nicholl and O’Cathain, 1989), with preterm infants tending to succumb to SIDS at a later postnatal age than fullterm infants (Malloy and Hoffman, 1995). The restricted age over which SIDS occurs clearly implicates developmental processes. Further investigation o f the form o f changes in HBIR activity during the first months of life is thus essential, particularly over the time scale o f the increasing HBIR activity noted between the actual and expected date o f delivery in preterm infants.