The effects of dichloroacetate in a rabbit model of acute hind-limb ischemia and reperfusion

Jeffrey S. Wilson, Greg Rushing, Brad L. Johnson, Jeffrey Kline, Jaime L. Parker, Andrew Bowser, Dennis F. Bandyk, Martin R. Back

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND: Dichloroacetate (DCA) is a drug that allows pyruvate dehydrogenase to remain active under anaerobic conditions by inhibiting the inactivating enzyme, pyruvate dehydrogenase kinase. We hypothesize that the administration of DCA during acute limb ischemia may have a beneficial effect by reducing the severity of anaerobic metabolism and lessening the irreversible injury. STUDY DESIGN: We studied a rabbit model using unilateral ligation of the iliac artery or femoral artery to evaluate two degrees of ischemia. After 2 hours of hind-limb ischemia, the animals were administered IV DCA (15 mg/kg) or an equivalent volume of saline. RESULTS: Higher serum lactate levels were seen after high compared to low ligation in control animals consistent with more severe ischemia. DCA treatment significantly reduced serum lactate levels after both high and low ligation. Similarly, the rise in percentage end-tidal CO 2 after reperfusion was less after DCA. All animals regained hind-limb function after the procedure, but ischemia or reperfusion resulted in appreciable muscle necrosis (> 10% area) in 50% of high- and 22% of low-ligation control animals. DCA treatment eliminated significant muscle necrosis in 100% of high-ligation animals. Muscle histology was similar in control and DCA-treated low-ligation animals. CONCLUSIONS: Treatment with DCA during acute arterial occlusion did significantly lower markers of anaerobic metabolism and reduced muscle necrosis in a rabbit model of acute hind-limb ischemia. DCA delivery through collateral blood flow may prolong the ischemia time interval before the onset of irreversible muscle injury and potential limb loss.

Original languageEnglish (US)
Pages (from-to)591-595
Number of pages5
JournalJournal of the American College of Surgeons
Volume197
Issue number4
DOIs
StatePublished - Oct 2003
Externally publishedYes

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Reperfusion
Ischemia
Extremities
Ligation
Rabbits
Muscles
Anaerobiosis
Necrosis
Lactic Acid
Iliac Artery
Wounds and Injuries
Femoral Artery
Carbon Monoxide
Serum
Pyruvic Acid
Histology
Oxidoreductases
Therapeutics
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Surgery

Cite this

The effects of dichloroacetate in a rabbit model of acute hind-limb ischemia and reperfusion. / Wilson, Jeffrey S.; Rushing, Greg; Johnson, Brad L.; Kline, Jeffrey; Parker, Jaime L.; Bowser, Andrew; Bandyk, Dennis F.; Back, Martin R.

In: Journal of the American College of Surgeons, Vol. 197, No. 4, 10.2003, p. 591-595.

Research output: Contribution to journalArticle

Wilson, Jeffrey S. ; Rushing, Greg ; Johnson, Brad L. ; Kline, Jeffrey ; Parker, Jaime L. ; Bowser, Andrew ; Bandyk, Dennis F. ; Back, Martin R. / The effects of dichloroacetate in a rabbit model of acute hind-limb ischemia and reperfusion. In: Journal of the American College of Surgeons. 2003 ; Vol. 197, No. 4. pp. 591-595.
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