Protective cardiovascular effects of diazepam in experimental acute chloroquine poisoning.
To assess the effects of diazepam in chloroquine poisoning, we studied pentobarbital anesthetized and mechanically ventilated pigs. All the pigs received 50 mg.kg-1 chloroquine given intravenously for 25 min. Eight pigs acted as control (group C). Another 7 were treated with diazepam given intravenously 5 min after the end of chloroquine infusion: 2 mg.kg-1 of diazepam for 2 min, then 1 mg.kg.h-1 for 25 min (group D). Thereafter, all pigs were sacrificed. In both groups the chloroquine infusion induced a large fall in arterial pressure, a decrease in heart rate, and an increase in QRS duration. No difference was observed between the 2 groups for weight, systolic and diastolic arterial pressures, heart rate, QRS and QT durations before diazepam. After diazepam, systolic and diastolic arterial pressures, heart rate, urine volume, urinary excretion of chloroquine, plasma and blood cell chloroquine levels were higher, whereas QRS duration was lower, in group D compared to group C. No difference was observed between the 2 groups for urinary concentration of chloroquine, the ratio between plasma and blood cell chloroquine levels, hepatic, cardiac, and skeletal muscle chloroquine levels, and QT duration. After diazepam, the slope of the regression curve between QRS duration and plasma chloroquine levels was reversed in group D compared to group C. We conclude that diazepam counteracts some haemodynamic and electrocardiographic changes, and increases urinary excretion of chloroquine, in acute experimental chloroquine poisoning.
Riou
B
B
Service de Réanimation Médicale, Hôpital de Bicêtre, Université Paris XI, Le Kremlin-Bicêtre, France.
Rimailho
A
A
Galliot
M
M
Bourdon
R
R
Huet
Y
Y
D000818:Animals; D002738:Chloroquine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000506:poisoning* / Q000652:urine; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D013552:Swine; D013997:Time Factors
D002738:Chloroquine; D003975:Diazepam