title: Plasmodium berghei: lactic acidosis and hypoglycaemia in a rodent model of severe malaria; effects of glucose, quinine, and dichloroacetate.
abstract: Fulminant malaria infections are characterised by hypoglycaemia and potentially lethal lactic acidosis. In young adult Wistar rats (n = 26) infected with Plasmodium berghei (ANKA strain), hyperparasitaemia (greater than 50%), anaemia (PCV 19.6 +/- 5.3%; mean +/- SD) hypoglycaemia (1.04 +/- 0.74 mmol/litre), hyperlactataemia (13.2 +/- 2.20 mmol/litre), hyperpyruvicaemia (0.51 +/- 0.12 mmol/litre) and metabolic acidosis (arterial pH 6.96 +/- 0.11) developed after approximately 14 days of infection. Hypoglycaemia was associated with appropriate suppression of plasma insulin concentrations. In a second series of experiments the metabolic effects of treatment with glucose (500 mg/kg/hr), quinine (5 mg/kg bolus followed by 10 mg/kg over 1 hr) and a potent activator of pyruvate dehydrogenase, dichloroacetate (300 mg/kg) were studied over a 1-hr period. In control animals quinine had no measurable effects, but dichloroacetate significantly reduced arterial blood lactate (74%) and pyruvate (80%). In infected animals, glucose infusion attenuated the rise in lactate (38% compared with 82%; P less than 0.01) but quinine had no additional metabolic effects. Dichloroacetate further attenuated the rise in lactate (14%; P less than 0.01).
authors.affiliation: Nuffield Department of Clincal Biochemistry, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: P A
authors.initials: PA
authors.lastname: Holloway
authors.forename: S
authors.initials: S
authors.lastname: Krishna
authors.forename: N J
authors.initials: NJ
authors.lastname: White
mesh_terms: D000136:Acid-Base Equilibrium; D000140:Acidosis, Lactic / Q000150:complications / Q000628:therapy; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005947:Glucose / Q000008:administration & dosage / Q000627:therapeutic use*; D006400:Hematocrit; D007003:Hypoglycemia / Q000150:complications / Q000628:therapy; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D008288:Malaria / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010100:Oxygen / Q000097:blood; D010962:Plasmodium berghei; D011773:Pyruvates / Q000097:blood; D011803:Quinine / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D002245:Carbon Dioxide; D003999:Dichloroacetic Acid; D011803:Quinine; D005947:Glucose; D010100:Oxygen