Bentley G A, Cullen L K, Reynoldson J A, Widdop R E
Br J Pharmacol. 1986 May;88(1):161-71. doi: 10.1111/j.1476-5381.1986.tb09483.x.
Experiments were undertaken to investigate a possible action of clonidine on venous haemodynamics, using cats and dogs with autoperfused hindquarters. This provided an arterial input to the region independent of cardiac output. Venous capacitance in the hindquarters was indicated by blood flow in the abdominal vena cava, as measured by an electromagnetic flow probe around this vessel. It was found that in both cats and dogs, clonidine given intravenously (5 micrograms kg-1 i.v.) or into the cisterna magna (1 microgram kg-1 i.c.m.) reduced mean arterial pressure and heart rate, but did not decrease hindquarter perfusion pressure. With the exception of dogs given i.v. clonidine, this drug caused a decrease in inferior vena cava (IVC) blood flow and this closely paralleled the hypotensive effect. However, when clonidine was given i.v. to dogs, the decrease in IVC blood flow preceded the hypotension. At the doses used, the reduction in IVC blood flow was larger following i.v. than i.c.m. clonidine in both species, and in all cases, it remained below control levels for at least 30 min, in spite of the constant arterial input to the region. In cats, dose-response curves were constructed to noradrenaline and adrenaline given into the perfusion circuit (i.a.) before and after clonidine. Following i.v. and i.c.m. clonidine, there was a selective depression of the venoconstrictor actions of the catecholamines, but no change in the arterial pressor action. Radiographic and latex studies in the dog and cat respectively were performed in order to visualize collateral blood flow that could account for the persistent decreases in IVC blood flow. In both species, intraspinal collateral flows were demonstrated which returned blood to the heart after ligation of the inferior vena cava below the renal veins. However, it was not possible to demonstrate radiographically any changes produced by clonidine in the collateral flow because of technical difficulties. These results suggest that clonidine causes a selective reduction in sympathetic tone to the veins that is mediated at least partly by a central action, as well as an expansion of the collateral venous routes. This, together with the selective impairment of venoconstrictor responses to both noradrenaline and adrenaline, may account for the decrease in cardiac output that is most often reported following clonidine.
采用后肢自身灌注的猫和狗进行实验，以研究可乐定对静脉血流动力学的可能作用。这为该区域提供了独立于心输出量的动脉输入。通过围绕腹静脉的电磁血流探头测量腹静脉血流来指示后肢的静脉容量。结果发现，在猫和狗中，静脉注射（5微克/千克体重静脉注射）或注入小脑延髓池（1微克/千克体重脑池内注射）可乐定均可降低平均动脉压和心率，但不降低后肢灌注压。除静脉注射可乐定的狗外，该药物导致下腔静脉（IVC）血流减少，且这与降压作用密切平行。然而，当给狗静脉注射可乐定时，IVC血流减少先于低血压出现。在所使用的剂量下，两种动物静脉注射可乐定后IVC血流的减少幅度均大于脑池内注射，并且在所有情况下，尽管该区域的动脉输入恒定，IVC血流至少在30分钟内仍低于对照水平。在猫中，在注射可乐定前后，分别构建了向灌注回路（动脉内）注射去甲肾上腺素和肾上腺素的剂量-反应曲线。静脉注射和脑池内注射可乐定后，儿茶酚胺的静脉收缩作用出现选择性抑制，但动脉升压作用无变化。分别对狗和猫进行了放射学和乳胶研究，以观察可能解释IVC血流持续减少的侧支血流情况。在两种动物中，均证实了脊髓内的侧支血流，即在肾静脉下方结扎下腔静脉后，血液回流至心脏。然而，由于技术困难，无法通过放射学方法显示可乐定对侧支血流产生的任何变化。这些结果表明，可乐定可导致对静脉的交感神经张力选择性降低，这至少部分是由中枢作用介导的，同时侧支静脉途径也有所扩张。这与对去甲肾上腺素和肾上腺素的静脉收缩反应的选择性损害一起，可能解释了可乐定给药后最常报道的心输出量减少。
