RESPIRATORY CONTROL--DETERMINANTS OF HYPOXIC GASPING

Project Details

Description

DESCRIPTION: Progressive brain
hypoxia in a glomectomized, vagotomized cat results in stereotyped changes
in the patterning of the phrenic neurogram. Initial depression of phrenic
amplitude progresses to apnea and gasping as the severity of hypoxia
increases. Gasping apparently serves as a means of "autoresuscitation" and
improves survival of animals, particularly neonates, if ambient oxygen is
restored. The main premise of this proposal is that gasping results from a
selective hypoxic depression of pontine structures which normally inhibit a
medullary gasping pattern generator. Three specific hypotheses will be
tested: 1) The brainstem has a rostral-to-caudal gradient of hypoxic
vulnerability. The applicant will compare the hypoxic response of pontile
and medullary respiratory outputs and measure extracellular [K+] in both
brain regions as an index of normal cellular function. To determine if
selective vulnerability results from a rostral-to-caudal gradient of tissue
hypoxia, tissue oxygenation will be measured in pons and medulla during
hypoxia. 2) The medullary gasping pattern generator is inhibited during
normoxia and disinhibited during hypoxia. These studies will test the
ability of the inhibitory neurotransmitters, gamma-aminobutyric acid (GABA)
and glycine, and their antagonists to modify gasping following
microinjection into the medullary gasping center. The applicant will test
the ability of GABA and glycine to abolish hypoxic gasping following
injection into this medullary site. Bicuculline and strychnine,
antagonists of GABA and glycine respectively, will be tested for their
ability to produce gasping in normoxic animals following medullary
microinjection. 3) Hypoxic gasping results from disinhibition of medullary
gasping pattern generator by the pons. This hypothesis will be tested by
determining whether electrical and chemical stimulation of the pontine
reticular formation inhibits hypoxic gasping. Since inhibitory
neurotransmitters are known to contribute to neuronal depression during
hypoxia, antagonists of GABA and glycine will be microinjected into the
pontine reticular formation during hypoxia to test whether reversal of
pontine inhibition will inhibition hypoxic gasping.
StatusFinished
Effective start/end date4/9/903/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health: $109,310.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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