Intravenous L-lactate application in minipigs partially protects acetylcholinesteratic but not butyrylcholinesteratic activity in plasma from inhibition by paraoxon.
OBJECTIVE
Intoxications with organophosphorous compounds such as paraoxon, an inhibitor of serine hydrolases, mainly butyrylcholinesterase and acetylcholinesterase, are frequent. Oximes are the only enzyme reactivators clinically available. In vitro studies have shown that L(+)-lactate reduces the inhibition of acetylcholinesteratic (AChEA) and butyrylcholinesteratic activity of plasma (BChEA) by paraoxon.


METHODS
The purpose of this in vivo study was to determine whether intravenous L(+)-lactate application under normoxic/normocapnic/normohydrogenemic conditions is able to protect AChEA and BChEA from paraoxon inhibition.


METHODS
University research institute.


METHODS
Eighteen female minipigs.


METHODS
Animals were anesthetized, intubated, and mechanically ventilated. Every animal received 1 mg of paraoxon per kilogram of body weight in 50 mL of saline over 50 mins. In addition to receiving paraoxon, six pigs of 18 received 2.5 g (0.125 g kg-1 of body weight) of intravenous L(+)-lactate in 50 mL of saline over 50 mins, and six other pigs received 10 g of L(+)-lactate (0.5 g kg-1 of body weight), whereas the six remaining served as controls.


RESULTS
In central venous blood, plasma acetylcholinesteratic and butyrylcholinesteratic activity were measured before paraoxon (baseline, 0 mins), immediately after paraoxon (50 mins after start), and 110, 170, 230, 290, 530, and 1010 mins after the start of infusion. Although 10 g of intravenous L(+)-lactate application had a statistically significant protective effect in vivo on AChEA, 2.5 g did not. No significant protective effect on BChEA was achieved with either 2.5 g or 10 g of L(+)-lactate.


CONCLUSIONS
Ten grams of L(+)-lactate can increase AChEA when administered simultaneously with paraoxon. Further study of the in vivo effects of L(+)-lactate after paraoxon intoxication and a formal comparison with standard oxime therapy seem warranted. Also, methods for achieving a prolonged elevated lactate concentration in vivo should be investigated.
Institute of Pharmacology and Toxicology, University of Heidelberg at Mannheim, Mannheim, Germany.
Wolfgang H
WH
Maleck
Nikola
N
Kern
Ulrike
U
Beha
Christina
C
Roth
Roderich
R
Rüfer
Georg A
GA
Petroianu
D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000187:drug effects* / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000008:administration & dosage*; D010261:Paraoxon / Q000494:pharmacology*; D013556:Swine, Miniature
D002800:Cholinesterase Inhibitors; D019344:Lactic Acid; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D010261:Paraoxon