Role of brain lactic acidosis in hypoxic depression of respiration.
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.
Neubauer
J A
JA
Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903-0019.
Simone
A
A
Edelman
N H
NH
D000140:Acidosis, Lactic / Q000503:physiopathology* / Q000517:prevention & control; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002248:Carbon Monoxide; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000503:physiopathology; D003714:Denervation; D003999:Dichloroacetic Acid / Q000494:pharmacology; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D010100:Oxygen / Q000097:blood; D010791:Phrenic Nerve / Q000503:physiopathology; D012119:Respiration
D007773:Lactates; D019344:Lactic Acid; D002248:Carbon Monoxide; D003999:Dichloroacetic Acid; D010100:Oxygen