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Treatment of Lactic Acidosis with Dichloroacetate in Dogs
Robert Park, … , William Leach, Virginia C. Lazarowitz
Robert Park, … , William Leach, Virginia C. Lazarowitz
Published October 1, 1982
Citation Information: J Clin Invest. 1982;70(4):853-862. https://doi.org/10.1172/JCI110682.
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Treatment of Lactic Acidosis with Dichloroacetate in Dogs

Abstract

Lactic acidosis is a clinical condition due to accumulation of H+ ions from lactic acid, characterized by blood lactate levels >5 mM and arterial pH <7.25. In addition to supportive care, treatment usually consists of intravenous NaHCO3, with a resultant mortality >60%. Dichloroacetate (DCA) is a compound that lowers blood lactate levels under various conditions in both man and laboratory animals. It acts to increase pyruvate oxidation by activation of pyruvate dehydrogenase. We evaluated the effects of DCA in the treatment of two different models of type B experimental lactic acidosis in diabetic dogs: hepatectomy-lactic acidosis and phenformin-lactic acidosis. The metabolic and systemic effects examined included arterial blood pH and levels of bicarbonate and lactate; the intracellular pH (pHi) in liver and skeletal muscle; cardiac index, arterial blood pressure and liver blood flow; liver lactate uptake and extrahepatic splanchnic (gut) lactate production; and mortality. Effects of DCA were compared with those of either NaCl or NaHCO3. The infusion of DCA and NaHCO3, delivered equal amounts of volume and sodium, although the quantity of NaHCO3 infused (2.5 meq/kg per h) was insufficient to normalize arterial pH.

Authors

Robert Park, Allen I. Arieff, William Leach, Virginia C. Lazarowitz

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Citations to this article (77)

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SP DiBartola, HA de Morais 		Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice 2012
Treatment of acute metabolic acidosis: a pathophysiologic approach
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Sodium Bicarbonate Treatment during Transient or Sustained Lactic Acidemia in Normoxic and Normotensive Rats
F Valenza, M Pizzocri, V Salice, G Chevallard, T Fossali, S Coppola, S Froio, F Polli, S Gatti, F Fortunato, GP Comi, L Gattinoni, O Kocher 		PloS one 2012
Critical care nephrology: management of acid–base disorders with CRRT
J Cerdá, AJ Tolwani, DG Warnock 		Kidney International 2011
Dichloroacetate stabilizes the intraoperative acid-base balance during liver transplantation
RE Shangraw, D Lohan-Mannion, A Hayes, RM Moriarty, R Fu, ST Robinson 		Liver Transplantation 2008
Anesthetic management of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) during laparotomy
N Sasano, Y Fujita, MH So, K Sobue, H Sasano, H Katsuya 		Journal of Anesthesia 2007
Sepsis
JM O’Brien, NA Ali, SK Aberegg, E Abraham 		The American Journal of Medicine 2007
Fluid, Electrolyte, and Acid-Base Disturbances in Liver Disease
SA Center 		Fluid Electrolyte and Acid-Base Disorders in Small Animal Practice 2006
Acid-Base Disorders and Their Treatment
L Hamm 		Acid-Base Disorders and Their Treatment 2005
Adjunctive therapies in sepsis: An evidence-based review:
A Cariou, C Vinsonneau, JF Dhainaut 		Critical Care Medicine 2004
Bench-to-bedside review: treating acid-base abnormalities in the intensive care unit - the role of buffers.
Gehlbach BK, Schmidt GA 		Critical Care 2004
Field level evaluation and risk assessment of the toxicity of dichloroacetic acid to the aquatic macrophytes Lemna gibba, Myriophyllum spicatum, and Myriophyllum sibiricum
ML Hanson, PK Sibley, SA Mabury, DC Muir, KR Solomon 		Ecotoxicology and Environmental Safety 2003
Treatment of metabolic acidosis:
J Levraut, D Grimaud 		Current Opinion in Critical Care 2003
Anaesthesia, Pain, Intensive Care and Emergency Medicine — A.P.I.C.E
A Gullo 		2001
Sodium Bicarbonate for the Treatment of Lactic Acidosis
SM Forsythe, GA Schmidt 		Chest 2000
Hyperventilation, épuration extrarénale et dichloroacétate dans le traitement des acidoses
M Guignier, JM Sturm, C Schwebel-Canali, D Barnoud, C Cracowski 		Réanimation Urgences 1999
Effects of dichloroacetate infusion on human skeletal muscle metabolism at the onset of exercise
RA Howlett, GJ Heigenhauser, E Hultman, MG Hollidge-Horvat, LL Spriet 		American journal of physiology. Endocrinology and metabolism 1999
Oncologic Therapies
EE Vokes, HM Golomb 		1999
Specific Therapies of Biguanide-induced Lactic Acidosis
JC Preiser, JL Vincent 		Anesthesiology 1998
Phenformin and lactic acidosis: a case report and review
SC Kwong, J Brubacher 		The Journal of Emergency Medicine 1998
Hepatic pyruvate dehydrogenase activity in humans: effect of cirrhosis, transplantation, and dichloroacetate
RE Shangraw, JM Rabkin, GD Lopaschuk 		AJP Gastrointestinal and Liver Physiology 1998
Pharmacokinetics of Dichloroacetate in Patients Undergoing Liver Transplantation
RE Shangraw, DM Fisher 		Anesthesiology 1996
Current concepts in acid-base balance: use of bicarbonate in patients with metabolic acidosis
AI Arieff 		Current Anaesthesia and Critical Care 1996
Effect of 2-chloropropionate on initial lactate uptake by rat skeletal muscle sarcolemmal vesicles
P Granier, H Dubouchaud, N Eydoux, J Mercier, C Préfaut 		Journal of applied physiology 1996
A Rapid Microassay for Dichloroacetate in Serum by Gel-Permeation Chromatography
Y Sakakihara, G Nakamura, Y Tokoeda, T Abe, S Kamoshita 		Clinical Chemistry and Laboratory Medicine 1994
The use of dichloroacetate in the treatment of overwhelming hypoxic acidosis
JA Wahr, K Ullrich, SF Boiling 		Journal of Cardiothoracic and Vascular Anesthesia 1994
Effects of 2-chloropropionate on venous plasma lactate concentration and anaerobic power during periods of incremental intensive exercise in humans
B Mercier, P Granier, J Mercier, F Anselme, G Ribes, C Prfaut 		European Journal of Applied Physiology and Occupational Physiology 1994
Hypoxia, Metabolic Acidosis, and the Circulation
AI Arieff 		1992
Effect of dichloroacetate on oxidative removal of lactate in mice after supramaximal exercise
H Hatta, R Soma, Y Atomi 		Comparative Biochemistry and Physiology Part B: Comparative Biochemistry 1991
Update 1991
JL Vincent 		1991
Tissue Oxygen Utilization
G Gutierrez, JL Vincent 		1991
Pseudoketogenesis in hepatectomized dogs
CD Rosiers, JA Montgomery, M Garneau, F David, OA Mamer, P Daloze, G Toffolo, C Cobelli, BR Landau, H Brunengraber 		American journal of physiology. Endocrinology and metabolism 1990
Buffer agents do not reverse intramyocardial acidosis during cardiac resuscitation
F Kette, MH Weil, M von Planta, RJ Gazmuri, EC Rackow 		Circulation 1990
Regulation of lactate metabolism in vivo
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The pharmacology of dichloroacetate
PW Stacpoole 		Metabolism 1989
The effect of dichloroacetate on the isolated no flow arrested rat heart
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Update 1989
JL Vincent 		1989
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Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease
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Effects of dichloroacetate following canine asphyxial arrest
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Comparison of sodium bicarbonate with dichloroacetate treatment of hyperlactatemia and lactic acidosis in the ischemic rat
RV Dimlich, MH Biros, DW Widman, J Kaplan 		Resuscitation 1988
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PR Young, WR Snyder, DA Vacante, CM Waickus, AP Zygas, F Grynspan, C Karunatilake, DH Wilson 		Medical Hypotheses 1988
Dichloroacetate inhibits glycolysis and augments insulin-stimulated glycogen synthesis in rat muscle
AS Clark, WE Mitch, MN Goodman, JM Fagan, MA Goheer, RT Curnow 		Journal of Clinical Investigation 1987
Dichloroacetate treatment of ischemic cerebral lactic acidosis in the fed rat
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MH Biros, RV Dimlich 		The American Journal of Emergency Medicine 1987
Dichloroacetate derivatives. metabolic effects and pharmacodynamics in normal rats
PW Stacpoole, MG Gonzalez, J Vlasak, Y Oshiro, N Bodor 		Life Sciences 1987
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RA Kreisberg 		Journal of Intensive Care Medicine 1987
Lactic acidosis
NE Madias 		Kidney International 1986
Dichloroacetic acid improves in vitro myocardial function following in vivo endotoxin administration
AH Burns, ME Giaimo, WR Summer 		Journal of Critical Care 1986
Postinsult treatment of ischemia-induced cerebral lactic acidosis in the rat
MH Biros, RV Dimlich, WG Barsan 		Annals of Emergency Medicine 1986
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A Bidani 		Medical Clinics of North America 1986
Effects of dichloroacetate in the treatment of hypoxic lactic acidosis in dogs
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Propionate transport in rat liver cells
P Fafournoux, C Rémésy, C Demigné 		Biochimica et Biophysica Acta (BBA) - Biomembranes 1985
L'acidose lactique
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Comparative metabolic effects of acetate and dichloroacetate infusion in the anesthetized dog
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Evidence for a Detrimental Effect of Bicarbonate Therapy in Hypoxic Lactic Acidosis
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5Lactic acidosis: Current concepts
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