Lohmöller G, Lohmöller R, Pfeffer M A, Pfeffer J M, Frohlich E D
Am Heart J. 1975 Apr;89(4):487-92. doi: 10.1016/0002-8703(75)90156-8.
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.
在22只麻醉开胸犬中研究了静脉注射氯噻嗪（每千克25毫克）的即刻血流动力学效应机制。给药后20分钟内，心输出量和每搏输出量显著下降；这与中心静脉压和左心室舒张末期压力降低有关。这些血流动力学效应是由利尿导致的血容量减少（尿量增加八倍）引起的，并依赖于此，这一点通过以下方式得以证明：当用6%的右旋糖酐纠正血容量减少（通过利尿）时，这些测量值恢复到对照水平；通过预防先前进行输尿管腔静脉吻合术的氯噻嗪治疗犬的血流动力学变化；以及通过定量等量出血证实相同的血流动力学效应。因此，氯噻嗪产生的即刻利尿导致血浆容量收缩（血细胞比容和血清蛋白浓度升高），进而减少心脏静脉回流、中心充盈压、每搏输出量和心输出量。没有证据表明噻嗪类药物有任何直接的心肌效应或外周静脉扩张作用。
