Volume 2 Supplement 1

Neural Control of Breathing

Open Access

Hypothermia and recovery from respiratory arrest in a neonatal rat in-vitro brainstem preparation

  • JL Feldman1,
  • NM Mellen1 and
  • WK Milsom2
Respiratory Research20012(Suppl 1):P11

https://doi.org/10.1186/rr127

Received: 2 August 2001

Published: 17 August 2001

In mammals, progressive hypothermia leads to loss of reflex responses, respiratory arrest, and finally, cardiac arrest and death. Under acute conditions in neonatal mammals, if progressive rewarming occurs soon enough, both the heart beat and breathing will resume spontaneously and they will recover fully but in adult rats, once respiratory arrest occurs, the animals must be artificially resuscitated. The mechanistic basis of the initial respiratory arrest in hypothermia as well as the ontogenetic changes in tolerance and in the ability of the system to autoresuscitate on rewarming are poorly understood. Onimura and Homma [1], demonstrated that when temperature was lowered from 26 to 24°C in an en bloc brainstem-spinal cord preparation from newborn rats, respiratory rate was depressed and bursts of activity in Pre-I neurons were not always followed by bursts of inspiratory activity in respiratory motor neurons. This suggested that either the number of active Pre-I neurons decreased and were no longer sufficient to activate the motor neuron pools, or that the threshold for the generation of inspiratory-modulated efferent activity in the motor neuron pools was raised, or both. This in turn suggested that respiratory arrest might occur at the level of pre-motor or motor neurons rather than at the level of the rhythm generator itself.

This study was designed to examine whether respiratory arrest during hypothermia occurs at the level of pre motor or motor neurons rather than at the level of the central rhythm generator itself. Specifically we sought to determine the consequences of hypothermic cooling until respiratory arrest, and subsequent re warming, on neurons in the preBötzinger Complex (via field potential recordings), as an indication of the output of the entire rhythmo-genic network; and from cervical spinal (phrenic) ventral roots (via suction electrode recording), as an indication of motor neuron output, in an in vitro neonatal rat brainstem-spinal cord preparation. With this preparation, progressive cooling slowed the frequency of fictive breathing with the cycle period increasing exponentially until respiratory related rhythmic activity ceased. There was no decrease in the peak, integrated sum or duration of the field potential during this process; ie, while slowing was progressive, arrest was not. The same was not completely true of the phrenic motor output. During progressive cooling there was a 14% fall in peak amplitude and a 32% fall in the integrated sum of the activity associated with each fictive burst. There were also rare instances at low temperature during both cooling and recovery where bursts of activity in the field potential were not accompanied by any increase in activity in the phrenic motor output. These data suggest that there must have been some increase in the threshold for generation of activity in the phrenic motor neuron pool relative to the neuron pool from which the field potential was recorded. Ultimate arrest, however, appears to occur at the level of the central rhythm generating network giving rise to complete and abrupt cessation of activation of the motor neuron pool(s).

On rewarming, the motor output often was fractionated suggesting that changes occurred in network synchronization either during cooling or during reactivation following hypothermic arrest.

Declarations

Acknowledgement

Supported by the NSERC of Canada and NIH grants HL40959 and HL37941.

Authors’ Affiliations

(1)
Department of Neurobiology, University of California
(2)
Department of Zoology, University of British Columbia

References

  1. Onimaru H, Homma I: Respiratory rhythm generator neurons in medulla of brainstem-spinal cord preparation from newborn rat. Brain Res. 1987, 403: 380-384. 10.1016/0006-8993(87)90080-1.PubMedView ArticleGoogle Scholar

Copyright

© BioMed Central Ltd 2001

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