Journal of Applied Physiology, Vol 63, Issue 2 699-706, Copyright © 1987 by American Physiological Society

ARTICLES

Naloxone reduces ventilatory depression of brain hypoxia

J. A. Neubauer, M. A. Posner, T. V. Santiago and N. H. Edelman
Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903-0019.

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 (VI) and ventral medullary surface pH (Vm pH) were measured in six anesthetized, peripherally chemodenervated cats. NLX consistently increased base-line hyperoxic VI from 618 +/- 99 to 729 +/- 126 ml/min (P less than 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 VI to 66 +/- 6% of base line before NLX and to 81 +/- 9% of base line after NLX (P less than 0.05). The difference in response after NLX was primarily the result of a linear increase in tidal volume (VT) with decreasing Vm pH (delta VT = 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 attenuation of the reduction in VI 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.

This article has been cited by other articles:

				P. Telgkamp, Y. Q. Cao, A. I. Basbaum, and J.-M. Ramirez Long-Term Deprivation of Substance P in PPT-A Mutant Mice Alters the Anoxic Response of the Isolated Respiratory Network J Neurophysiol, July 1, 2002; 88(1): 206 - 213. [Abstract] [Full Text] [PDF]

				S. D. LEE, H. NAKANO, L. E. GOSSELIN, J. A. KRASNEY, E. H. SCHLENKER, and G. A. FARKAS Endogenous Opioids Modulate Ventilation and Peak Oxygen Consumption in Obese Zucker Rats Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 1009 - 1015. [Abstract] [Full Text]