Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge

Walter J May; Fraser Henderson Jr; Ryan B Gruber; Joseph F Discala; Alex P Young; James N Bates; Lisa A Palmer; Stephen J Lewis

doi:10.4236/ojmip.2013.33019

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Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge

Journal article

Open access

Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge

Walter J May, Fraser Henderson Jr, Ryan B Gruber, Joseph F Discala, Alex P Young, James N Bates, Lisa A Palmer and Stephen J Lewis

Open journal of molecular and integrative physiology, Vol.3(3), pp.134-145

08/28/2013

DOI: 10.4236/ojmip.2013.33019

PMCID: PMC4103749

PMID: 25045592

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Abstract

This study explored the concept that morphine has latent deleterious actions on the ventilatory control systems that respond to a hypoxic-hypercapnic challenge. In this study, we examined the ventilatory responses elicited by hypoxic-hypercapnic challenge in conscious rats at a time when the effects of morphine (10 mg/kg) on arterial blood-gas chemistry and minute ventilation had subsided. Morphine induced pronounced changes in arterial blood-gas chemistry (e.g., an increase in pCO 2 , decreases in pO 2 and sO 2 ) and decreases in minute ventilation. Despite the complete resolution of the morphine-induced changes in arterial blood-gas chemistry and minute ventilation and almost complete resolution of the effects on peak inspiratory flow and peak expiratory flow, subsequent exposure to hypoxic-hypercapnic challenge elicited markedly blunted increases in minute ventilation and in peak inspiratory and expiratory flows. These findings demonstrate that (1) the changes in arterial blood-gas chemistry elicited by morphine parallel changes in minute ventilation rather than PIF and PEF, and (2) morphine has latent untoward effects on the ventilatory responses to hypoxic-hypercapnic challenge. These novel findings raise the possibility that patients deemed to have recovered from the acute ventilatory depressant effects of morphine may still be susceptible to the latent effects of this opioid analgesic. The mechanisms underlying these latent effects remain to be elucidated.

Hypoxia-Hypercapnia

Morphine

Arterial Blood Gases

Minute Ventilation

Conscious Rats

Details

Title: Subtitle: Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge
Creators: Walter J May - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Fraser Henderson Jr - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Ryan B Gruber - Division of Biology, Galleon Pharmaceuticals, Horsham, PA 19044, USA
Joseph F Discala - Division of Biology, Galleon Pharmaceuticals, Horsham, PA 19044, USA
Alex P Young - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
James N Bates - Department of Anesthesia, University of Iowa College of Medicine, Iowa City, IA 52240, USA
Lisa A Palmer - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Stephen J Lewis - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Resource Type: Journal article
Publication Details: Open journal of molecular and integrative physiology, Vol.3(3), pp.134-145
DOI: 10.4236/ojmip.2013.33019
PMID: 25045592
PMCID: PMC4103749
NLM abbreviation: Open J Mol Integr Physiol
ISSN: 2162-2159
eISSN: 2162-2167
Language: English
Date published: 08/28/2013
Academic Unit: Anesthesia
Record Identifier: 9984006493002771

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