[Trends of tissue hypoxia following chemotherapy of acute malaria in mice].
The effects of antimalarial treatment on the blood oxygen-transporting properties and on the tissue hypoxia were investigated in severe murine malaria, using mice infected with Plasmodium berghei (NK65). Five week old male ddY mice were inoculated intraperitoneally with 1 X 10(7) of P. berghei-infected red blood cells and treated with Fansidar (20 mg/kg body weight sulfadoxine and 1 mg/kg body weight pyrimethamine orally) on day 5 after inoculation. Parasitemia in these mice decreased rapidly on day 1 after treatment. Blood hemoglobin concentration, however, decreased on days 1 and 2 of treatment, then began to increase. The actual oxygen equilibrium curve (OEC) in vivo (actual pH; actual Pco2; 36.5 degrees C) was calculated from the measured OEC and the results of blood gas analysis. Looking from arterial and venous Po2 of each group, blood oxygen-transporting properties decreased markedly on day 2 of treatment. This decrease resulted mainly from the decrease of hemoglobin concentration and also partly from the raised hemoglobin affinity for oxygen. Adenosine triphosphate concentration in liver tissues, however, began to increase on day 1 of treatment. Adenylate energy charge of liver tissues also recovered on day 1. Blood glucose concentration began to increase and blood lactate concentration began to decrease simultaneously on day 1 of treatment. Glucose concentration in liver tissues, in contrast, decreased on days 1 and 2 of inoculation. Lactate concentration in liver tissue decreased earlier on day 1. These data indicate that tissue hypoxia was removed on day 1 following antimalarial treatment although blood oxygen-transporting properties decreased on days 1 and 2 after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Hioki
A
A
Department of Parasitology, Gifu University School of Medicine.
Ohtomo
H
H
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects*; D004338:Drug Combinations; D008288:Malaria / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010100:Oxygen / Q000097:blood; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*
D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D010100:Oxygen; D011739:Pyrimethamine