Journal of Applied Physiology, Vol 65, Issue 3 1324-1331, Copyright © 1988 by American Physiological Society

ARTICLES

Role of brain lactic acidosis in hypoxic depression of respiration

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

The role of lactic acidosis of progressive brain hypoxia (PBH) as both a central chemoreceptor stimulant and a general respiratory depressant was assessed by preventing lactate formation both locally and globally with dichloroacetate (DCA). Phrenic nerve activity (PN) and ventral medullary pH (Vm pH) responses to PBH (1% CO-40% O2-balance N2) were determined in anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats while fraction of end-tidal CO2 (FETCO2) and mean arterial blood pressure (MABP) were maintained constant. Topical DCA near the central chemoreceptors prevented the progressive Vm acidosis of PBH and was associated with a slightly greater depression of PN for any given level of brain hypoxia [75 +/- 12% base-line mock cerebrospinal fluid compared with 63 +/- 11% base-line topical DCA at O2 content of arterial blood (CaO2) of 7.5 ml O2/dl]. Systemic DCA also prevented the progressive acidosis of PBH and significantly altered the profile of depression with PBH. Before DCA, PBH produced a progressive reduction in PN after reducing CaO2 by 20%. After DCA, PN was not significantly depressed until CaO2 was reduced to very low levels, whereupon there was a sharp decline in PN. Before DCA, reducing CaO2 to 6 ml O2/dl reduced PN by 41 +/- 16%, whereas after DCA there was no significant reduction in PN (4 +/- 5%). We conclude that 1) lactic acidosis near the central chemosensitive regions does produce a small stimulation of respiration during PBH but that 2) the overwhelming response to central lactic acidosis of PBH is respiratory depression.

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