L-Cysteine ethyl ester reverses the deleterious effects of morphine on, arterial blood-gas chemistry in tracheotomized rats

James Mendoza, Rachael Passafaro, Santhosh Baby, Alex P. Young, James N. Bates, Benjamin Gaston, Stephen J. Lewis

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

This study determined whether the membrane-permeable ventilatory stimulant, l-cysteine ethylester (l-CYSee), reversed the deleterious actions of morphine on arterial blood-gas chemistry in isoflurane-anesthetized rats. Morphine (2mg/kg, i.v.) elicited sustained decreases in arterial blood pH, pO2 and sO2, and increases in pCO2 (all responses indicative of hypoventilation) and alveolar-arterial gradient (indicative of ventilation-perfusion mismatch). Injections of l-CYSee (100μmol/kg, i.v.) reversed the effects of morphine in tracheotomized rats but were minimally active in non-tracheotomized rats. l-cysteine or l-serine ethylester (100μmol/kg, i.v.) were without effect. It is evident that l-CYSee can reverse the negative effects of morphine on arterial blood-gas chemistry and alveolar-arterial gradient but that this positive activity is negated by increases in upper-airway resistance. Since l-cysteine and l-serine ethylester were ineffective, it is evident that cell penetrability and the sulfur moiety of l-CYSee are essential for activity. Due to its ready penetrability into the lungs, chest wall muscle and brain, the effects of l-CYSee on morphine-induced changes in arterial blood-gas chemistry are likely to involve both central and peripheral sites of action.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalRespiratory Physiology and Neurobiology
Volume189
Issue number1
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

Keywords

  • Arterial blood-gas chemistry
  • Halothane-anesthetized rats
  • L-Cysteine ethylester
  • Morphine

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