D-Lactic acid-induced neurotoxicity in a calf model.
Lactic acidosis (DAC) occurs as a complication of short-bowel syndrome in humans and in a variety of other gastrointestinal disorders in monogastrics and ruminants. DAC is associated with signs of impaired central nervous system (CNS) function including ataxia and coma. The objective of this experiment was to determine whether either acidification of nervous tissue or d-lactic acid is responsible for decreased neurological function. Eight Holstein calves (32 +/- 11 days, 70 +/- 10 kg) were surgically catheterized with indwelling intravenous jugular and atlanto-occipital space cerebrospinal fluid (CSF) catheters and infused for 6 h in random order with isomolar dl-lactic acid (dl-LA), l-lactic acid (l-LA), hydrochloric acid (HCl), or saline. dl-LA induced ataxia after 4 h of infusion and produced the greatest obtunding of CNS function (at 7 h, score 8.0 +/- 0.4), whereas the other infusions caused neither ataxia nor scores over 1.5 (P < 0.01 from dl-LA). dl-LA induced significantly less acidemia than HCl (at 6 h pH 7.13 +/- 0.06 and 7.00 +/- 0.04, base excess -16 +/- 1 and -23 +/- 3 mmol/l, bicarbonate 11 +/- 1 and 8 +/- 1 mmol/l respectively, all P < 0.01) but greater than l-LA and saline (P < 0.01). CSF changes followed a similar but less pronounced pattern. Although HCl infusion produced a severe acidemia and CSF acidosis, only minor effects on neurological function were evident suggesting that d-lactate has a direct neurotoxic effect that is independent of acidosis. Conversely, l-LA produced only minor neurological changes.
Abeysekara
Saman
S
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Naylor
Jonathan M
JM
Wassef
Andrew W A
AW
Isak
Ulyana
U
Zello
Gordon A
GA
D000140:Acidosis, Lactic / Q000503:physiopathology*; D000818:Animals; D001259:Ataxia / Q000209:etiology; D002417:Cattle; D006851:Hydrochloric Acid / Q000494:pharmacology; D019344:Lactic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D023421:Models, Animal; D009424:Nervous System Physiological Phenomena; D020258:Neurotoxicity Syndromes / Q000097:blood / Q000134:cerebrospinal fluid / Q000209:etiology*
D019344:Lactic Acid; D006851:Hydrochloric Acid