Author(s)

Walter J. May¹, Fraser Henderson Jr.¹, Ryan B. Gruber², Joseph F. Discala², Alex P. Young¹, James N. Bates³, Lisa A. Palmer¹, Stephen J. Lewis^4*

¹Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, USA.
²Division of Biology, Galleon Pharmaceuticals, Horsham, USA.
³Department of Anesthesia, University of Iowa College of Medicine, Iowa City, USA.
⁴Department of Pediatrics, Case Western Reserve University, Cleveland, USA.

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 pCO₂, decreases in pO₂ and sO₂) 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 depresssant 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.

Morphine; Hypoxia-Hypercapnia; Minute Ventilation; Arterial Blood Gases; Conscious Rats

May, W. , Henderson Jr., F. , Gruber, R. , Discala, J. , Young, A. , Bates, J. , Palmer, L. and Lewis, S. (2013) Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge. Open Journal of Molecular and Integrative Physiology, 3, 134-145. doi: 10.4236/ojmip.2013.33019.