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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fenoldopam (Corlopam), a new dopaminergic agent in clinical development by SmithKline Beecham Pharmaceuticals, is a dopamine-1 (DA1) agonist at post-synaptic dopamine receptors. Preclinical and clinical studies have demonstrated that it is a potent renal vasodilator as well as a peripheral vasodilator. In both normal volunteers and hypertensive patients intravenous fenoldopam causes dose-related decreases in blood pressure and important increases in renal hemodynamics and function including increased renal blood flow, diuresis and natriuresis. Fenoldopam does not alter glomerular filtration. Intravenous fenoldopam has been demonstrated to be efficacious in severe hypertensive patients in several multicenter, multinational trials. In severe hypertension efficacy trials fenoldopam was judged to be as effective as sodium nitroprusside and to produce less serious side effects. In patients with moderate to severe heart failure, fenoldopam has been demonstrated to produce dose-related acute increases in cardiac output, stroke volume and work index, decreased systemic vascular resistance but no important changes in pulmonary wedge pressure or right atrial pressure. In CHF patients fenoldopam has been demonstrated to be as efficacious as sodium nitroprusside. Fenoldopam, as a specific (DA1) agonist resulting in decreased peripheral and renal vascular resistance, diuresis, natriuresis and increases in cardiac hemodynamics on intravenous administration, appears to be an efficacious agent which offers a reasonable alternative in the treatment of severe hypertension and acute congestive heart failure.
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PMID:Clinical experience with intravenous fenoldopam. 197 40

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.
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PMID:Beneficial effects of fenoldopam on systemic and regional hemodynamics in rabbits with congestive heart failure. 245 54

Fenoldopam, a newly developed intravenous dopaminergic DA1 receptor agonist, was used in an open, prospective study for blood pressure control in 12 patients presenting with hypertensive crisis. At a dose of 0.2-0.5 microgram kg-1 min-1 fenoldopam decreased systolic blood pressure from 209 +/- 13 to 151 +/- 17 mmHg and diastolic blood pressure from 114 +/- 10 to 78 +/- 10 mmHg. Blood pressure was controlled in all 12 patients within 5-50 min. In none of the patients did rebound hypertension occur upon termination of the study medication, nor was any adverse event reported. Major hemodynamic changes induced by fenoldopam were a decrease in total peripheral resistance from 1853 +/- 611 to 1193 +/- 368 and in pulmonary vascular resistance from 252 +/- 170 to 180 +/- 74 dyne s-1 cm-5. In patients with high left ventricular filling pressure at study pulmonary capillary wedge pressure decreased while the stroke volume index and mixed venous oxygen saturation increased under fenoldopam. Thus, fenoldopam appears to be a rapid-acting, well-tolerated, and highly effective intravenous substance for the treatment of severe hypertension.
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PMID:Hemodynamic profile of intravenous fenoldopam in patients with hypertensive crisis. 790

Fenoldopam, a selective DA1-receptor agonist, infused intravenously for 24 hours (0.6 +/- 0.3 microgram/kg/min, range 0.1-1.5) in 25 patients with NYHA functional class III or IV heart failure, produced a prompt and sustained hemodynamic response. Cardiac index rose from an average preinfusion baseline value of 1.8 to 2.6/l min. Stroke volume index increased from 19 to 26 ml/m2 and stroke work index increased from 18 to 25 g M/m2. These changes were accompanied by a reduction in systemic vascular resistance from an average of 2400 to 1500 dynes sec/cm5. There was no change in the heart rate or right atrial pressure. There was a transient reduction in the left ventricular filling pressure from 25 to 20 mmHg. Urinary sodium excretion did not change significantly. Transient asymptomatic thrombocytopenia developed in four patients. The drug was well tolerated by all patients. These results suggest that continuous intravenous infusion of fenoldopam is safe and produces favorable hemodynamic responses in severe heart failure. However, unlike its effects in patients with hypertension, it failed to produce sustained natriuresis in these patients.
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PMID:Intravenous fenoldopam infusion in severe heart failure. 809 27

Patients with polycystic kidney disease (PKD) are characterized with uncontrolled hypertension. Hypertension in PKD is a ciliopathy, an abnormal function and/or structure of primary cilia. Primary cilia are cellular organelles with chemo and mechanosensory roles. In the present studies, we designed a cilia-targeted (CT) delivery system to deliver fenoldopam specifically to the primary cilia. We devised the iron oxide nanoparticle (NP)-based technology for ciliotherapy. Live imaging confirmed that the CT-Fe2O3-NPs specifically targeted primary cilia in cultured cells in vitro and vascular endothelia in vivo. Importantly, the CT-Fe2O3-NPs enabled the remote control of the movement and function of a cilium with an external magnetic field, making the nonmotile cilium exhibit passive movement. The ciliopathic hearts displayed hypertrophy with compromised functions in left ventricle pressure, stroke volume, ejection fraction, and overall cardiac output because of prolonged hypertension. The CT-Fe2O3-NPs significantly improved cardiac function in the ciliopathic hypertensive models, in which the hearts also exhibited arrhythmia, which was corrected with the CT-Fe2O3-NPs. Intraciliary and cytosolic Ca2+ were increased when cilia were induced with fluid flow or magnetic field, and this served as a cilia-dependent mechanism of the CT-Fe2O3-NPs. Fenoldopam-alone caused an immediate decrease in blood pressure, followed by reflex tachycardia. Pharmacological delivery profiles confirmed that the CT-Fe2O3-NPs were a superior delivery system for targeting cilia more specifically, efficiently, and effectively than fenoldopam-alone. The CT-Fe2O3-NPs altered the mechanical properties of nonmotile cilia, and these nano-biomaterials had enormous clinical potential for ciliotherapy. Our studies further indicated that ciliotherapy provides a possibility toward personalized medicine in ciliopathy patients.
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PMID:Ciliotherapy: Remote Control of Primary Cilia Movement and Function by Magnetic Nanoparticles. 3086 Aug 8