To assess whether endogenous opioids participate in respiratory depression due to brain hypoxia, we determined the ventilatory response to progressive carboxyhemoglobinemia (1% CO, 40% O2) before and after administration of naloxone (NLX, 0.1 mg/kg iv). Minute ventilation (V̇I) and ventral medullary surface pH (Vm pH) were measured in six anesthetized, peripherally chemodenervated cats. NLX consistently increased base-line hyperoxic V̇I from 618 ± 99 to 729 ± 126 ml/min (P < 0.05). Although NLX did not alter the Vm pH response to CO [initial alkalosis, Vm pH 0.011 ± +0.003 pH units, followed by acidosis, Vm pH -0.082 ± 0.036 at carboxyhemoglobin (HbCO) 55%], NLX attenuated the amount of ventilatory depression; increasing HbCO to 55% decreased V̇I to 66 ± 6% of base line before NLX and to 81 ± 9% of base line after NLX (P < 0.05). The difference in response after NLX was primarily the result of a linear increase in tidal volume (VT) with decreasing Vm pH (ΔVT = 60.3 ml/-pH unit) which was absent before NLX. To assess whether the site of action of the endogenous opioid effect was the central chemosensors, the ventilatory and Vm pH response to progressive HbCO was determined in three additional cats before and after topical application of NLX (3 x 10-4 M) to the ventral medullary surface. The effect of topical NLX was similar to systemic NLX; significant attentuation of the reduction in V̇I with increasing HbCO. We conclude that 1) endogenous opioids mediate a portion of the depression of ventilation due to acute brain hypoxia and 2) this effect is probably at the central chemosensitive regions.
All Science Journal Classification (ASJC) codes
- Physiology (medical)