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. 2013 Aug 28;3(3):134-145.
doi: 10.4236/ojmip.2013.33019.

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

Walter J May  1 , Fraser Henderson  1 , Ryan B Gruber  2 , Joseph F Discala  2 , Alex P Young  1 , James N Bates  3 , Lisa A Palmer  1 , Stephen J Lewis  1
Affiliations

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

Walter J May et al. Open J Mol Integr Physiol. .

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 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 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.

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

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Figures

Figure 1
Figure 1
Changes in frequency of breathing (top panel), tidal volume (middle panel) and minute ventilation (lower panel) elicited by injections of vehicle or morphine (10 mg/kg, i.v.) and subsequent exposure to Hypoxia-Hypercapnia (air flow off) and return to room-air (air flow on). The data are presented as mean ± SEM. There were 6 rats in each group.
Figure 2
Figure 2
Changes in Inspiratory time (upper panel), expiratory time (middle panel) and end inspiratory pause (lower panel) elicited by injections of vehicle or morphine (10 mg/kg, i.v.) and subsequent exposure to Hypoxia-Hypercapnia (air flow off) and return to room-air (air flow on). The data are presented as mean ± SEM. There were 6 rats in each group.
Figure 3
Figure 3
Changes in peak inspiratory flow (upper panel), peak expiratory flow (middle panel) and body temperature (bottom panel) elicited by injections of vehicle or morphine (10 mg/kg, i.v.) and subsequent exposure to Hypoxia-Hypercapnia (air flow off) and return to room-air (air flow on). The data are presented as mean ± SEM. There were 6 rats in each group.
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