3 research outputs found
Postnatal development of central rhythm generation of breathing in mammals
The objective of this thesis was to investigate some of the developmental changes that
occur in central rhythm generation of breathing in mammals. Specifically, progressive
hypothermia was used as a tool to investigate the mechanism of respiratory arrest at
very low body temperatures and autoresuscitation upon re-warming. Both in vivo and in
vitro techniques were used; the first to identify the point in development when the ability
to autoresuscitate from hypothermia-induced respiratory arrest was lost in mammals
and the second to determine if the ability of neonatal mammals to autoresuscitate was
dependent upon the persistent sodium current (lNap). Experiments were conducted
upon neonates and juveniles of a cold-intolerant species, the rat, and a cold-tolerant
species, the hamster.
In vivo experiments revealed that the ability to autoresuscitate was lost in rats between
14 and 20 days after birth and in hamsters between 28 days after birth and adulthood.
The time scale over which the ability to autoresuscitate was lost was similar to the time
scale over which these animals developed adult-type endothermy and homeothermy. It
was hypothesised that the loss of the ability to autoresuscitate over development
corresponded to changes in the mechanism of rhythm generation of breathing.
Pacemaker properties, primarily dependent upon lNap , were hypothesised to be the
mechanism by which autoresuscitation from hypothermia-induced respiratory arrest
occurred. A shift in the relative important of pacemaker properties and network
properties of rhythm generation of breathing during the postnatal development of
mammals could explain the loss of the ability to autoresuscitate.
In order to examine the role of lNap-dependent pacemaker properties in respiratory
rhythm generation and the phenomenon of autoresuscitation from hypothermia-induced
respiratory arrest, riluzole was used to block lNap in en bloc preparations from neonatal
rats and hamsters. Riluzole of two concentrations was bath applied, both at constant
temperature and after fictive respiratory arrest at very low temperatures. In neonatal
rats, riluzole failed to inhibit rhythm generation and autoresuscitation and instead
appeared to block network bursting properties, important for pattern generation. These
results are consistent with the hypothesis that lNap-dependent pacemaker properties are
not essential for rhythm generation in neonatal rats and that respiratory rhythm in this
species is instead produced by a heterogenous population of pacemakers including
both lNap-dependent and lNap-independent cells. In contrast, blockade of lNap with
riluzole produced fictive respiratory failure in preparations from hamsters via a decline in
the frequency of bursting indicating that lNap was essential for the generation of
respiratory rhythm in this species. Blockade of lNap also blocked autoresuscitation
entirely in 67% of hamster preparations. These findings are consistent with the
hypothesis that lNap-dependent pacemaker properties are essential for the generation of
respiratory rhythm in neonatal hamsters and that these properties are important in the
process of autoresuscitation from hypothermia-induced respiratory arrest.Science, Faculty ofZoology, Department ofGraduat
Riluzole disrupts autoresuscitation from hypothermic respiratory arrest in neonatal hamsters but not rats
9 page(s
Developmental changes in cold tolerance and ability to autoresuscitate from hypothermic respiratory arrest are not linked in rats and hamsters
In adult mammals, severe hypothermia leads to respiratory and cardiac arrest, followed by death. Neonatal rats and hamsters can survive much lower body temperatures and, upon artificial rewarming, spontaneously recover from respiratory arrest (autoresuscitate), typically suffering no long-term effects. To determine developmental and species differences in cold tolerance (defined here as the temperature of respiratory arrest) and its relation to the ability to autoresuscitate, we cooled neonatal and juvenile Sprague-Dawley rats and Syrian hamsters until respiration ceased, followed by rewarming. Ventilation and heartbeat were continuously monitored. In rats, cold tolerance did not change throughout development, however the ability to autoresuscitate from hypothermic respiratory arrest did (lost between postnatal days, P, 14 and 20), suggesting that the mechanisms for maintaining breathing at low temperatures was retained throughout development while those initiating breathing on rewarming were altered. Hamsters, however, showed increased cold tolerance until P26-28 and were able to autoresuscitate into adulthood (provided the heart kept beating throughout respiratory arrest). Also, hamsters were more cold tolerant than rats. We saw no evidence of gasping to initiate breathing following respiratory arrest, contributing to the hypothesis that hypothermic respiratory arrest does not lead to anoxia. (C) 2012 Elsevier B.V. All rights reserved