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

Abstract

The aim of this study was to determine whether morphine depresses the ventilatory responses elicited by a hypoxic challenge (10% O₂, 90% N₂) in conscious rats at a time when the effects of morphine on arterial blood gas (ABG) chemistry, Alveolar-arterial (A-a) gradient and minute ventilation (V_M) had completely subsided. In vehicle-treated rats, each episode of hypoxia stimulated ventilatory function and the responses generally subsided during each normoxic period. Morphine (5 mg/kg, i.v.) induced an array of depressant effects on ABG chemistry, A-a gradient and V_M (via decreases in tidal volume). Despite resolution of these morphine-induced effects, the first episode of hypoxia elicited substantially smaller increases in V_M than in vehicle-treated rats, due mainly to smaller increases in frequency of breathing. The pattern of ventilatory responses during subsequent episodes of hypoxia and normoxia changed substantially in morphine-treated rats. It is evident that morphine has latent deleterious effects on ventilatory responses elicited by hypoxic challenge.

Keywords: arterial blood gas chemistry; conscious rats; hypoxia; minute ventilation; morphine.

Figure 1

Temporal changes in arterial blood gas chemistry values and Alveolar-arterial (A-a) gradient elicited by bolus injections of vehicle or morphine (5 mg/kg, i.v.) in conscious rats. There were 8 rats in each group. The data are mean ± SEM. *P < 0.05, significant change from Pre values.

Figure 2

Changes in frequency of breathing (upper panel), tidal volume (middle panel) and Minute Volume (lower panel) elicited by injections of vehicle or morphine (5 mg/kg, i.v.) and subsequent exposure to three 15 min episodes of hypoxia (10% O₂, 90% N₂) each of which was followed by a 15 min period of normoxia (room-air). The first episode of hypoxia began 15 min after injection of vehicle or morphine. There were 6 rats in each group. Data are mean ± SEM.

Figure 3

Changes in inspiratory time (top panel), expiratory time (middle panel) and end inspiratory pause (bottom panel) elicited by injections of vehicle or morphine (5 mg/kg, i.v.) and subsequent exposure to three 15 min episodes of hypoxia (10% O₂, 90% N₂) each of which was followed by a 15 min period of normoxia (room-air). The first episode of hypoxia began 15 min after injection of vehicle or morphine. There were 6 rats in each group. Data are mean ± SEM.

Figure 4

Changes in tidal volume/inspiratory time (upper panel), peak inspiratory flow (middle panel), and peak expiratory flow (bottom panel) elicited by injections of vehicle or morphine (5 mg/kg, i.v.) and subsequent exposure to three 15 min episodes of hypoxia (10% O₂, 90% N₂) each of which was followed by a 15 min period of normoxia (room-air). The first episode of hypoxia began 15 min after injection of vehicle or morphine. There were 6 rats in each group. Data are mean ± SEM.

Figure 5

Changes in body temperature elicited by injections of vehicle (upper panel) or morphine (5 mg/kg, i.v., lower panel) and subsequent exposure to three 15 min episodes of hypoxia (10% O₂, 90% N₂) each of which was followed by 15 min periods of normoxia (room-air). The first episode of hypoxia began 15 min after injection of vehicle or morphine. There were 8 rats in each group. Data are mean ± SEM.