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 electrol yte parameters. In the first protocol, six groups of rats were studied to determine whether changes in ventricular fibrillation threshold, a nd serum and myocardial potassium occur after treatment with different doses of hydrochlorothiazide; three groups (N = 15) served as control s and the other three groups (N = 15) were given different doses of hy drochlorothiazide for a 3 month period. Two rats from each group were sacrificed daily. One rat heart was perfused using the Langendorff per fusion apparatus and the other used for myocardial potassium analysis. Blood was also collected for serum potassium analysis. There was no c hange in the threshold for ventricular fibrillation in groups treated with 0.04 mg and 0.09 mg hydrochlorothiazide compared to control value s. There was a nonsignificant decrease in serum and myocardial potassi um 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 hydroc hlorothiazide showed significantly lower ventricular fibrillation thre shold levels and decreased serum potassium (P<0.02) compared to contro l 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 fibrillati on threshold and serum potassium levels (P<0.05). A significant decrea se 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 hydrochlorothiaz ide have no effect on ventricular fibrillation threshold level or on s erum or myocardial potassium levels. There was a significant decrease in ventricular fibrillation threshold and serum and myocardial potassi um 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 hydrochloroth iazide and these variables were corrected by the intragastric administ ration of potassium salts.