The effect of a low dose versus a conventional dose of hydrochlorothiazide on ventricular fibrillation threshold and electrolyte levels in laboratory rats.
We studied the effect of hydrochlorothiazide on metabolic and electrolyte parameters. In the first protocol, six groups of rats were studied to determine whether changes in ventricular fibrillation threshold, and serum and myocardial potassium occur after treatment with different doses of hydrochlorothiazide; three groups (N = 15) served as controls and the other three groups (N = 15) were given different doses of hydrochlorothiazide for a 3 month period. Two rats from each group were sacrificed daily. One rat heart was perfused using the Langendorff perfusion apparatus and the other used for myocardial potassium analysis. Blood was also collected for serum potassium analysis. There was no change in the threshold for ventricular fibrillation in groups treated with 0.04 mg and 0.09 mg hydrochlorothiazide compared to control values. There was a nonsignificant decrease in serum and myocardial potassium levels in rats treated with 0.04 mg and 0.09 mg hydrochlorothiazide compared to control. Seven of the 15 rats treated with 0.18 mg hydrochlorothiazide showed significantly lower ventricular fibrillation threshold levels and decreased serum potassium (P < 0.02) compared to control animals. In addition, a significant decrease in myocardial potassium was noted (P < 0.05). In the second protocol, 8 of the 15 rats treated with 0.18 mg hydrochlorothiazide showed reduced ventricular fibrillation threshold and serum potassium levels (P < 0.05). A significant decrease in myocardial potassium was also observed (P < 0.05). These variables were corrected by the intragastric administration of potassium salts. The present study indicates that 0.04 mg and 0.09 mg hydrochlorothiazide have no effect on ventricular fibrillation threshold level or on serum or myocardial potassium levels. There was a significant decrease in ventricular fibrillation threshold and serum and myocardial potassium levels in 7 of the 15 animals studied in protocol one and 8 of the 15 animals studied in protocol two, treated with 0.18 mg hydrochlorothiazide and these variables were corrected by the intragastric administration of potassium salts.
Khedun
S M
SM
Department of Experimental and Clinical Pharmacology, University of Natal Medical School, South Africa.
Maharaj
B
B
Naicker
T
T
D000818:Animals; D004232:Diuretics; D004573:Electrolytes / Q000032:analysis*; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000378:metabolism
D004232:Diuretics; D004573:Electrolytes; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D011188:Potassium