Journal article
l-Cysteine ethyl ester reverses the deleterious effects of morphine on, arterial blood–gas chemistry in tracheotomized rats
Respiratory physiology & neurobiology, Vol.189(1), pp.136-143
10/01/2013
DOI: 10.1016/j.resp.2013.07.007
PMCID: PMC4430552
PMID: 23892097
Abstract
•l-CYSee minimally affected the negative actions of morphine on arterial blood–gas chemistry (ABG) in non-tracheotomized rats.•l-CYSee reversed the negative actions of morphine in tracheotomized rats.•l-Cysteine or l-SERee did not alter the actions of morphine on ABG in tracheotomized rats.•l-CYSee reverses morphine effects on ABG but this positive activity is negated by increases in upper-airway resistance.•Cell penetrability and the sulfur moiety drive l-CYSee activity.
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.
Details
- Title: Subtitle
- l-Cysteine ethyl ester reverses the deleterious effects of morphine on, arterial blood–gas chemistry in tracheotomized rats
- Creators
- James Mendoza - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USARachael Passafaro - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USASanthosh Baby - Division of Biology, Galleon Pharmaceuticals, Horsham, PA 19044, USAAlex P Young - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USAJames N Bates - Department of Anesthesiology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USABenjamin Gaston - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USAStephen J Lewis - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
- Resource Type
- Journal article
- Publication Details
- Respiratory physiology & neurobiology, Vol.189(1), pp.136-143
- DOI
- 10.1016/j.resp.2013.07.007
- PMID
- 23892097
- PMCID
- PMC4430552
- NLM abbreviation
- Respir Physiol Neurobiol
- ISSN
- 1569-9048
- eISSN
- 1878-1519
- Publisher
- Elsevier B.V
- Grant note
- name: Galleon Pharmaceuticals
- Language
- English
- Date published
- 10/01/2013
- Academic Unit
- Anesthesia
- Record Identifier
- 9984007292302771
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