Mechanism of immediate hemodynamic effects of chlorothiazide.
The mechanism of the immediate hemodynamic effects of intravenous chlorothiazide (25 mg. per kilogram) was studied in 22 anesthetized open-chest dogs. Within 20 minutes after administration, cardiac output and stroke volume significantly fell; this was associated with decreased central venous and left ventricular end-diastolic pressures. That these hemodynamic effects were caused by, and dependent upon, volume loss through diuresis (eightfold increase in urine volume) was shown: by a return of these measurements to control levels when the volume loss (by diuresis) was corrected with 6 per cent Dextran; by prevention of the hemodynamic changes in chlorthiazide-treated dogs previously prepared with ureterocaval anastomosis; and by confirming these same hemodynamic effects by quantitatively equivalent hemorrhage. Thus, the immediate diuresis produced by chlorothiazide resulted in a contracted plasma volume (increased hematocrit and serum protein concentration) which, in turn, diminished cardiac venous return, central filling pressures, stroke volume, and cardiac output. There was no evidence demonstrated to indicate any direct myocardial effect or peripheral venodilation induced by thiazide.
D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000032:analysis; D002302:Cardiac Output / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D002712:Chlorides / Q000032:analysis; D002740:Chlorothiazide / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000503:physiopathology; D008297:Male; D011188:Potassium / Q000032:analysis; D012964:Sodium / Q000032:analysis; D014513:Ureter / Q000601:surgery; D014682:Vena Cava, Inferior / Q000601:surgery; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D001798:Blood Proteins; D002712:Chlorides; D002740:Chlorothiazide; D012964:Sodium; D011188:Potassium