Jover B F, McGrath B P
Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
J Cardiovasc Pharmacol. 1988 Apr;11(4):483-8. doi: 10.1097/00005344-198804000-00016.
Fenoldopam (SKF 82526 J) is a selective DA-1 receptor agonist and thus of a potential benefit for promoting afterload reduction, renal vasodilatation, and diuresis in congestive heart failure. To examine the acute effects of fenoldopam in heart failure, studies were performed in control rabbits (n = 6) and in rabbits with chronic congestive heart failure (CHF, n = 6) induced by adriamycin treatment. Cardiovascular variables and regional blood flows were determined before and after an infusion of fenoldopam (150 micrograms/kg total dose). Resting hemodynamics differed in CHF and control groups. In the CHF group, mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) were reduced and right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP), and total peripheral resistance (TPR) were increased. Renal blood flow was much reduced in the CHF as compared with the control group (5.1 +/- 0.8 vs. 9.1 +/- 0.6 ml/min.g, p less than 0.05). Similar falls in MAP were noted after fenoldopam in CHF (-13 +/- 2%) and control rabbits (-12 +/- 3%) due to falls in TPR. An increase in CO was observed in both groups, the rise being more pronounced in the CHF group (22 vs. 12%). Heart rate was unchanged by fenoldopam in CHF rabbits but increased in controls. After fenoldopam, CHF rabbits exhibited significantly greater increases in blood flow to each of the three vascular beds studied: renal (113 +/- 27% vs. 7 +/- 13%), mesenteric (249 +/- 60% vs. 15 +/- 19%) and cerebral (145 +/- 13% vs. 12 +/- 12%). Plasma renin and norepinephrine (NE) levels increased after fenoldopam in both control and CHF rabbits. These results show that acute administration of fenoldopam produces favourable systemic and regional hemodynamic responses in rabbits with low output heart failure. However, long-term benefit remains to be demonstrated, particularly considering the hormonal responses.
非诺多泮（SKF 82526 J）是一种选择性DA-1受体激动剂，因此对于促进充血性心力衰竭患者的后负荷降低、肾血管舒张和利尿可能有益。为了研究非诺多泮在心力衰竭中的急性作用，对对照组家兔（n = 6）和经阿霉素治疗诱导的慢性充血性心力衰竭（CHF，n = 6）家兔进行了研究。在输注非诺多泮（总剂量150微克/千克）前后测定心血管变量和局部血流量。CHF组和对照组的静息血流动力学不同。在CHF组中，平均动脉压（MAP）、心输出量（CO）和每搏量（SV）降低，右心房压（RAP）、左心室舒张末期压力（LVEDP）和总外周阻力（TPR）升高。与对照组相比，CHF组的肾血流量显著减少（5.1±0.8对9.1±0.6毫升/分钟·克，p<0.05）。由于TPR下降，CHF家兔（-13±2%）和对照家兔（-12±3%）在输注非诺多泮后MAP出现类似下降。两组均观察到CO增加，CHF组的升高更为明显（22%对12%）。非诺多泮对CHF家兔的心率无影响，但使对照家兔的心率增加。输注非诺多泮后，CHF家兔所研究的三个血管床中的每一个的血流量均显著增加：肾（113±27%对7±13%）、肠系膜（249±60%对15±19%）和脑（145±13%对12±12%）。在对照和CHF家兔中，输注非诺多泮后血浆肾素和去甲肾上腺素（NE）水平均升高。这些结果表明，急性给予非诺多泮可在低输出量心力衰竭家兔中产生有利的全身和局部血流动力学反应。然而，长期益处仍有待证实，尤其是考虑到激素反应。
