Michael W Moore

Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, United States

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Publications (3)8.46 Total impact

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    ABSTRACT: The hypothesis was that an orexin 2 receptor (OX2R) agonist would prevent sleep-related disordered breathing.
    Respiratory Physiology & Neurobiology 06/2014; · 2.05 Impact Factor
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    ABSTRACT: Although central to the susceptibility of adult diseases characterized by abnormal rhythmogenesis, characterizing the genes involved is a challenge. We took advantage of the C57BL/6J (B6) trait of hypoxia-induced periodic breathing and its absence in the C57BL/6J-Chr 1(A/J)/NaJ chromosome substitution strain to test the feasibility of gene discovery for this abnormality. Beginning with a genetic and phenotypic analysis of an intercross study between these strains, we discovered three quantitative trait loci (QTLs) on mouse chromosome 1, with phenotypic effects. Fine-mapping reduced the genomic intervals and gene content, and the introgression of one QTL region back onto the C57BL/6J-Chr 1(A/J)/NaJ restored the trait. mRNA expression of non-synonymous genes in the introgressed region in the medulla and pons found evidence for differential expression of three genes, the highest of which was apolipoprotein A2, a lipase regulator; the apo a2 peptide fragment (THEQLTPLVR), highly expressed in the liver, was expressed in low amounts in the medulla but did not correlate with trait expression. This work directly demonstrates the impact of elements on mouse chromosome 1 in respiratory rhythmogenesis.
    Journal of Applied Physiology 04/2012; 113(1):167-74. · 3.48 Impact Factor
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    ABSTRACT: Background: H(2)S synthesis inhibitors (HSSI) have been shown to impact respiratory control. For instance, the HSSI hydroxylamine (HA) decreases the respiratory discharge rate from isolated medullary sections, and HA in addition to other HSSIs propargylglycine and amino-oxyacetic acid (AOAA) have been found to reduce hypoxic responsiveness. Objectives: The aim of this study was to determine if administration of HSSIs could improve respiratory stability in an intact organism prone to recurrent central apneas. Methods: Saline and HSSI compounds were administered to C57BL/6J mice (n = 24), a strain predisposed to recurrent central apneas, prior to measurement of hypoxic and posthypoxic ventilatory behavior. Results: Administration of HA and AOAA resulted in a significantly smaller percentage of animals expressing one or more apneas during reoxygenation compared to saline control, and animals given AOAA demonstrated a smaller coefficient of variation for frequency during reoxygenation, a marker suggesting greater respiratory stability. This occurred despite varying effects of the three HSSI compounds on hypoxic ventilatory response. Conclusions: Instability and pause expression are improved by targeting H(2)S synthesis, an effect not predicted by effects on hypoxic responsiveness.
    Respiration 09/2011; 82(6):522-9. · 2.92 Impact Factor

Publication Stats

5 Citations
8.46 Total Impact Points

Institutions

  • 2014
    • Louis Stokes Cleveland VA Medical Center
      Cleveland, Ohio, United States
  • 2011–2012
    • Case Western Reserve University
      • Division of Pulmonary, Critical Care and Sleep Medicine
      Cleveland, OH, United States
    • Case Western Reserve University School of Medicine
      Cleveland, Ohio, United States