Shebuski R J, Smith J M, Ruffolo R R
Department of Pharmacology, Smith Kline & French Laboratories, Swedeland, Pa.
Pharmacology. 1988;36(1):35-43. doi: 10.1159/000138344.
The renal and pulmonary hemodynamic effects of fenoldopam, dobutamine, dopamine and norepinephrine were compared in the pentobarbital-anesthetized dog. Animals were pretreated with propranolol (1 mg/kg, i.v.) to eliminate beta-adrenoceptor-mediated effects in the renal and pulmonary circulations. Heparinized blood was withdrawn from the right femoral artery and transferred, via a peristaltic pump, to the pulmonary arterial branch supplying the left diaphragmatic lobe of the lung. The flow rate of the pump was set so that the perfusion pressure in the lobe was equal to resting diastolic pulmonary artery blood pressure. Under these conditions of constant flow, changes in perfusion pressure reflect changes in pulmonary vascular resistance. Renal blood flow was measured in the same experiments via an electromagnetic flow probe which was placed directly on the left renal artery. Intraarterial administration of fenoldopam resulted in a marked reduction in renal vascular resistance at doses that had virtually no effect on pulmonary vascular resistance. Conversely, dobutamine increased pulmonary vascular resistance slightly, and had no effect on the renal circulation. Dopamine increased pulmonary vascular resistance at all doses, and exhibited a biphasic effect on renal vascular resistance. At low doses, dopamine produced a modest reduction in renal vascular resistance, and at higher doses, dopamine significantly increased renal vascular resistance. Norepinephrine increased both pulmonary and renal vascular resistance at all doses, as expected. These results indicate that fenoldopam may be hemodynamically favorable over dobutamine and dopamine in the management of patients with low output cardiac failure since fenoldopam improves renal hemodynamics at doses that have little or no effect on the pulmonary circulation.
在戊巴比妥麻醉的犬中比较了非诺多泮、多巴酚丁胺、多巴胺和去甲肾上腺素对肾脏和肺脏的血流动力学影响。动物预先用普萘洛尔（1毫克/千克，静脉注射）处理，以消除肾脏和肺循环中β-肾上腺素能受体介导的效应。从右股动脉抽取肝素化血液，并通过蠕动泵将其输送到供应肺左膈叶的肺动脉分支。设置泵的流速，使该叶的灌注压力等于静息舒张压肺动脉血压。在这些恒定流量条件下，灌注压力的变化反映了肺血管阻力的变化。在相同实验中，通过直接放置在左肾动脉上的电磁流量探头测量肾血流量。动脉内给予非诺多泮在对肺血管阻力几乎无影响的剂量下可导致肾血管阻力显著降低。相反，多巴酚丁胺使肺血管阻力略有增加，对肾循环无影响。多巴胺在所有剂量下均增加肺血管阻力，对肾血管阻力表现出双相作用。低剂量时，多巴胺使肾血管阻力适度降低，高剂量时，多巴胺显著增加肾血管阻力。如预期的那样，去甲肾上腺素在所有剂量下均增加肺和肾血管阻力。这些结果表明，在治疗低心输出量心力衰竭患者时，非诺多泮在血流动力学方面可能优于多巴酚丁胺和多巴胺，因为非诺多泮在对肺循环影响很小或无影响的剂量下可改善肾脏血流动力学。
