Effect of dichloroacetate sodium on the lactacidemia of experimental endotoxin shock

G. F. Merrill, M. Rosolowsky

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

We have investigated the influence of dichloroacetate sodium (DCA) on changes in selected metabolic and hemodynamic variables during lethal endotoxemia, focusing mainly on DCA's lactate-lowering effects. All experiments were conducted in overnight-fasted, male New Zealand white rabbits. E coli endotoxin (0.25 mg/kg IV) produced 80% mortality in 24 hours and significantly (P <0.001) increased lactic acid concentrations greater than eight-fold (16.4 ± 3.9 to 140 ± 11.2 mg/dl). Pretreatment with DCA (350 mg/kg IV) in a second group of similarly challenged rabbits reduced lethality (LD20) and attenuated the marked hyperlactacidemia (18.2 ± 4.5 to 56 ± 9.1 mg/dl). In a third group, administering DCA (350 mg/kg) 90 minutes after the E coli injection decreased the endotoxin-induced lactacidemia from 104.3 ± 9.5 mg/dl to 47.9 ± 6.9 mg/dl 3 hours later, yet only slightly improved 24-hour survival (LD71). Hyperglycemia (66-70% increases) occurred in all groups postendotoxin administration (with and without DCA), but the magnitudes of the increase were not significantly different amongst groups. Plasma corticosterone levels increased following the endotoxin challenge with the greatest change occurring in the DCA-pretreatment group. Heart rate, systemic arterial pressure, hematocrit and arterial PO2 changed modestly in all groups, while PCO2 and pH decreased. The samllest decrement in the latter two variables occurred in the DCA-pretreatment group. We conclude that DCA is effective in lowering the hyperlactacidemia of experimental endotoxemia and that its potential usefulness in the short-term treatment of clinical lactacidemias merits further attention.

Original languageEnglish (US)
Pages (from-to)13-21
Number of pages9
JournalCirculatory shock
Volume7
Issue number1
StatePublished - 1980

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Effect of dichloroacetate sodium on the lactacidemia of experimental endotoxin shock'. Together they form a unique fingerprint.

Cite this