Flaim S F, Zelis R
J Pharmacol Exp Ther. 1982 Aug;222(2):359-66.
The present study was conducted to determine the effect of a "calcium channel blocker," diltiazem (DZ), on cardiovascular dynamics and the distribution of total cardiac output in the conscious rat. Animals were instrumented for right atrial, left ventricular, arterial and venous pressure recordings and the radioactive microsphere technique was used to measure regional blood flow and cardiac output before (control) and during the intravenous infusion of either DZ at three dosage levels (0.4, 2.0, and 10.0 mg/kg/hr) or saline placebo at rates matching those of the DZ protocol (0.015, 0.1 and 0.5 ml/min). Maximum volume infusion rate equaled approximately a 2% increase in blood volume/minute. Systemic vascular resistance, stroke volume, regional vascular resistances and the regional percent distribution of total cardiac output were calculated. In the experimental group (n = 9, body weight = 404 +/- 7 g), DZ, at the highest dose, caused a nonsignificant increase in cardiac output of 61% (cardiac output decreased in one animal) and a significant drop in systemic vascular resistance (45%) while no changes occurred in the control group (n = 5, body weight = 440 +/- 9 g). The major effect of DZ was to increase blood flow and reduce vascular resistance in the coronary circulation (percent distribution of total cardiac output to the coronary circulation, control vs. maximum infusion: saline placebo, 3.9 +/- 0.5 to 4.5 +/- 0.4%; DZ, 3.5 +/- 0.5 to 6.9 +/- 0.5%, P less than .01). The results indicate that DZ does not suppress cardiac function and may actually increase cardiac output secondary to afterload reduction. DZ results in a balanced increase in regional blood flow and no major change in total cardiac output distribution in the conscious rat.
本研究旨在确定“钙通道阻滞剂”地尔硫䓬(DZ)对清醒大鼠心血管动力学及总心输出量分布的影响。对动物进行仪器植入,以记录右心房、左心室、动脉和静脉压力,并采用放射性微球技术在静脉输注三种剂量水平(0.4、2.0和10.0mg/kg/hr)的DZ或生理盐水安慰剂(输注速率与DZ方案匹配,即0.015、0.1和0.5ml/min)之前(对照)和期间测量局部血流量和心输出量。最大容量输注速率约等于血容量每分钟增加2%。计算全身血管阻力、每搏输出量、局部血管阻力和总心输出量的局部百分比分布。在实验组(n = 9,体重 = 404 ± 7g)中,最高剂量的DZ使心输出量非显著性增加61%(有一只动物的心输出量下降),全身血管阻力显著下降(45%),而对照组(n = 5,体重 = 440 ± 9g)未发生变化。DZ的主要作用是增加冠状动脉循环中的血流量并降低血管阻力(总心输出量在冠状动脉循环中的百分比分布,对照与最大输注:生理盐水安慰剂,3.9 ± 0.5至4.5 ± 0.4%;DZ,3.5 ± 0.5至6.9 ± 0.5%,P <.01)。结果表明,DZ不会抑制心脏功能,实际上可能因后负荷降低而增加心输出量。DZ可使清醒大鼠局部血流量均衡增加,总心输出量分布无重大变化。