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G D Shorten - One of the best experts on this subject based on the ideXlab platform.
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effects of Fenoldopam on renal blood flow and its function in a canine model of rhabdomyolysis
European Journal of Anaesthesiology, 2005Co-Authors: Clare Murray, F Markos, H M Snow, T B Corcoran, Nollaig A Parfrey, G D ShortenAbstract:Summary Background and objective: Our hypothesis was that Fenoldopam, a selective DA 1 agonist, would protect against rhabdomyolysis-induced renal injury. Methods: We studied the effects of intravenous Fenoldopam (0.1–1.0 μg kg −1 min −1 ) or saline on renal blood flow and function in 10 anaesthetized Labrador dogs in whom rhabdomyolysis and myoglobinuric acute renal failure had been induced by administration of glycerol 50% (10 mL kg −1 ) intramuscularly. Haemodynamic measurements including renal blood flow and derived parameters of renal function including creatinine clearance were recorded before and for the 30 min following glycerol injection, and during the 3 h following commencement of each infusion. Serum malondialdehyde concentrations were measured before and 15 min after glycerol intramuscularly, and 30 and 150 min after commencement of the infusion. Results: In the Fenoldopam group, creatinine clearance was less than placebo at 1 and 2 h after commencing the infusion (12.7 ± 11.5 versus 31.3 ± 9.9 mL min −1 , P = 0.04; 8.5 ± 5.3 versus 20.1 ± 7.4 mL min −1 , P = 0.03). A 140-fold increase in serum malondialdehyde concentration occurred in one dog (Fenoldopam group). Conclusion: Fenoldopam increased the severity of the renal injury in this canine model of myoglobinuric acute renal failure.
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effects of prophylactic Fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs
Critical Care Medicine, 2001Co-Authors: Michele Halpenny, F Markos, Henry M Snow, Patrick F Duggan, E Gaffney, Damian P Oconnell, G D ShortenAbstract:Objective: It was hypothesized that Fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of Fenoldopam (0.1 μg.kg -1 .min -1 ) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. Design: Prospective, randomized, controlled experiment. Setting: University-based animal laboratory and research unit. Subjects: Eight female beagle dogs. Interventions: Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of Fenoldopam or normal saline; b) during infusion of Fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of Fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. Measurements and Main Results: Administration of Fenoldopam (0.1 μg.kg -1 .min -1 ) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 ± 20 to 47 ± 6 mUmin and 0.26 ± 0.15 to 0.08 ± 0.05 mUmin, respectively) but not in the Fenoldopam group (75 ± 14 to 73 ± 17 mUmin and 0.3 ± 0.19 to 0.14 ± 0.05 mUmin, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 ± 0.4 to 1.8 ± 0.8 mL.kg -1 .min -1 and 1.7% ± 0.9% to 0.4% ± 0.2%, respectively) but not in the dogs that received Fenoldopam (3.0 ± 1.0 to 2.9 ± 0.5 mL.kg -1 .min -1 and 1.9% ± 1.1% to 1.7% ± 2.7%, respectively). Conclusions: Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that Fenoldopam may have a renoprotective effect in acute ischemic injury.
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the effects of Fenoldopam on renal blood flow and tubular function during aortic cross clamping in anaesthetized dogs
European Journal of Anaesthesiology, 2000Co-Authors: Michele Halpenny, F Markos, Henry M Snow, Patrick F Duggan, E Gaffney, Damian P Oconnell, G D ShortenAbstract:Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Fenoldopam, a selective dopamine agonist, may increase renal blood flow and decrease tubular oxygen consumption. The objective of this study was to quantify the effects of Fenoldopam (0.1 μg kg -1 min -1 ) on renal blood flow and renal tubular function in anaesthetized dogs that have undergone aortic cross clamping. Eight labrador dogs were selected to receive either saline or Fenoldopam (0.1 μg kg -1 min -1 ) intravenously. Arterial pressure, heart rate, renal blood flow, urinary output, fractional excretion of sodium, creatinine clearance and lithium clearance were measured (a) prior to infusions of saline or Fenoldopam (b) 1 h after commencing the infusion (c) during a 90-min period of infrarenal aortic cross-clamping with concurrent infusion of Fenoldopam or saline and (d) for 1 h after simultaneous aortic declamping and discontinuation of the infusions. There was no haemodynamic instability upon commencing the infusion of Fenoldopam (0.1 μg kg -1 min -1 ). Creatinine clearance (2.03 ± 0.5-2.45 ± 0.3 mL min -1 kg -1 (mean±SD)), urine output (0.23 ± 0.16-0.35 ± 0.23 mL min -1 (mean ± SD)), and fractional excretion of sodium (0.7 ± 0.52-1.3 ± 0.73% (mean ± SD)) increased (P < 0.05), following commencement of the Fenoldopam infusion. Fractional excretion of sodium (1.2 ± 0.7% (mean±SD)) and urine output (0.36 ± 0.21 mL min -1 (mean ± SD)) were maintained during the aortic cross-clamp period (P < 0.05). Renal blood flow increased when the Fenoldopam infusion was commenced (145 ± 43.3-161 ± 39.2 mL min -1 (mean ± SD)) and remained greater than baseline during the aortic cross-clamping period (152 ± 44 mL min -1 (mean±SD)), although these increases did not reach statistical significance. The most striking abnormalities observed by electron microscopy were marked disruption of the microvillus brush border in proximal tubules, vacuolation and separation of epithelial cells on basolateral infolds. The changes were similar in the two groups. In conclusion Fenoldopam (0.1 μg kg -1 min -1 ) may have renoprotective effects which persist during infrarenal aortic cross clamping.
Robert R Luther - One of the best experts on this subject based on the ideXlab platform.
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the effects of Fenoldopam a selective dopamine receptor agonist on systemic and renal hemodynamics in normotensive subjects
Critical Care Medicine, 1999Co-Authors: Vandana Mathur, Suzanne K Swan, Lawrence J Lambrecht, Shakeel Anjum, Jere Fellmann, Dawn Mcguire, Murray Epstein, Robert R LutherAbstract:Objective: Acute renal fallure, frequently a consequence of renal vasoconstriction and subsequent renal Ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, Fenoldopam rapidly decreases blood pressure, Increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of Fenoldopam that Increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects. Design: Randomized, double-blind, placebo-controlled, crossover study. Setting: Clinical research unit. Patients: Fourteen normal male volunteers. Interventions: Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of Fenoldopam (0.03, 0.1, and 0.3 μg/kg/min) on both high-sodium and a low-sodium diet. Measurements and Main Results: Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 ± 148 vs. 576 ± 85 mL/min at 0.03 μg/kg/min; 777 ± 172 vs. 579 ± 80 mL/min at 0.1 μg/kg/min; and 784 ± 170 vs. 592 ± 165 mL/min at 0.3 μg/kg/min (p <.05 Fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 μg/kg/min), significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate. At 0.1 and 0.3 μg/kg/ min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the Fenoldopam group than in the placebo group: 62.5 ± 6.4 vs. 63.6 ± 2.6 mm Hg, respectively, at 0.3 μg/kg/min (p <.05). None of the effects of Fenoldopam were altered by volume status. Conclusions: Fenoldopam Increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate. These findings will be useful in designing future studies exploring the role of Fenoldopam in preventing or treating renal failure in patients who are not hypertensive.
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The effects of Fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in normotensive subjects
Critical Care Medicine, 1999Co-Authors: Vandana Mathur, Suzanne K Swan, Lawrence J Lambrecht, Shakeel Anjum, Jere Fellmann, Dawn Mcguire, Murray Epstein, Robert R LutherAbstract:Objective: Acute renal fallure, frequently a consequence of renal vasoconstriction and subsequent renal Ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, Fenoldopam rapidly decreases blood pressure, Increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of Fenoldopam that Increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects. Design: Randomized, double-blind, placebo-controlled, crossover study. Setting: Clinical research unit. Patients: Fourteen normal male volunteers. Interventions: Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of Fenoldopam (0.03, 0.1, and 0.3 μg/kg/min) on both high-sodium and a low-sodium diet. Measurements and Main Results: Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 ± 148 vs. 576 ± 85 mL/min at 0.03 μg/kg/min; 777 ± 172 vs. 579 ± 80 mL/min at 0.1 μg/kg/min; and 784 ± 170 vs. 592 ± 165 mL/min at 0.3 μg/kg/min (p
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prolonged Fenoldopam infusions in patients with mild to moderate hypertension pharmacodynamic and pharmacokinetic effects
American Journal of Hypertension, 1999Co-Authors: Addison A Taylor, Robert R Luther, Roberto Mangookarim, Kevin D Ballard, Alexander M M Shepherd, William Polvino, Sarat Sunthornyothin, James L PoolAbstract:Abstract Thirty-three patients with mild-to-moderate essential hypertension received either placebo or Fenoldopam, a selective dopamine-1 agonist, by intravenous infusion at a fixed infusion rate ranging from 0.1 to 0.8 μg/kg/min for 48 h during a double-blind, placebo-controlled, randomized inpatient clinical trial. Blood pressure and heart rate were measured every 15 min for 24 h before, during, and 24 h after the 48-h drug infusion. Plasma concentrations of racemic Fenoldopam were measured at frequent intervals during and for 24 h after Fenoldopam infusion. In the 26 patients who received Fenoldopam, there were dose-dependent reductions in systolic and diastolic blood pressure, which usually reached a nadir within 2 h of beginning infusion and were significant even at the lowest dose studied ( − 9 and − 9 mm Hg for systolic and diastolic blood pressure, respectively, at 24 h for the dose of 0.04 μg/kg/min, P .05). There were associated increases in heart rate that were greater in the first than in the last 24 h of drug infusion. Compared to the average 24-h control blood pressure, maximum mean reductions in systolic and diastolic blood pressures of 33 and 21 mm Hg, respectively, were noted in patients receiving Fenoldopam at 0.8 μg/kg/min and occurred 4 and 1 h, respectively, after beginning infusion. Tolerance to the blood pressure lowering effects of the drug developed slowly during the 48 h of drug infusion; the half-life for this effect was 60 h. No serious adverse clinical effects were noted in any patient. These results demonstrate that Fenoldopam is effective in reducing blood pressure of patients with mild-to-moderate hypertension at doses as low as 0.04 μg/kg/min, is well tolerated at doses up to 0.8 μg/kg/min, maintains most of its antihypertensive efficacy throughout 48 h of continuous, constant rate infusion, and produces neither prolonged pharmacodynamic effects nor rebound hypertension when discontinued. The pharmacodynamic effects of the drug are best predicted by pharmacokinetics of racemic and R-Fenoldopam.
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Fenoldopam a new parenteral antihypertensive consensus roundtable on the management of perioperative hypertension and hypertensive crises
American Journal of Hypertension, 1999Co-Authors: Suzanne Oparil, Jerrold H Levy, Murray Epstein, Robert R Luther, Richard C Prielipp, Solomon Aronson, Michael G Deeb, Addison A TaylorAbstract:Abstract A panel of clinicians from anesthesiology, surgery, nephrology, hypertension, cardiology, and pharmacology was convened to discuss pharmacologic therapeutics in the management of hypertensive crisis and perioperative hypertension. The panel discussed the advantages and limitations of currently available parenteral drugs, and assessed the potential use of Fenoldopam mesylate, a drug in clinical development since 1981, and recently approved by the U.S. Food and Drug Administration (FDA). Fenoldopam is a dopamine receptor (DA1 selective) agonist that is a systemic and renal vasodilator. It was concluded that Fenoldopam offers significant advantages as a parenterally administered agent for the management of blood pressure in both hypertensive emergencies and in the perioperative setting.
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sustained hemodynamic effects of the selective dopamine 1 agonist Fenoldopam during 48 hour infusions in hypertensive patients a dose tolerability study
The Journal of Clinical Pharmacology, 1999Co-Authors: Addison A Taylor, Robert R Luther, Roberto Mangookarim, Kevin D Ballard, James L PoolAbstract:Eight patients with stage I-II hypertension received a continuous IV infusion of the selective dopamine-1 agonist, Fenoldopam, for up to 48 hours at rates from 0.4 to 1.9 micrograms/kg/min. Hemodynamics and clinical symptoms during infusion were compared to the same parameters in the 24-hour periods before and after infusion. Fenoldopam lowered blood pressure and increased heart rate. Greatest changes occurred during the first 12 hours of infusion and gradually returned toward preinfusion values throughout the remaining 36 hours in the six patients who completed 48 hours of infusion. Fenoldopam was discontinued within 2 hours of starting the infusion in two patients who received drug rates of 0.9 microgram/kg/min and 1.9 micrograms/kg/min because of precipitous bradycardia. Clinical symptoms noted at Fenoldopam doses higher than 0.8 microgram/kg/min were headache, dizziness, diaphoresis, nausea and vomiting, and restlessness. In this pilot study, Fenoldopam effectively reduced blood pressure in patients with stage I-II hypertension for up to 48 hours, but fixed-dose infusion rates above 0.8 microgram/kg/min were associated with a high frequency of clinically significant and often intolerable adverse effects.
Samin K Sharma - One of the best experts on this subject based on the ideXlab platform.
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changing trends in incidence and predictors of radiographic contrast nephropathy after percutaneous coronary intervention with use of Fenoldopam
American Journal of Cardiology, 2002Co-Authors: Annapoorna Kini, Cristina A Mitre, Mazullah Kamran, Javed Suleman, Mary E Duffy, Jonathan D Marmur, Samin K SharmaAbstract:showed that selective dopa-mine-1 receptor agonist Fenoldopam protects againstcontrast-mediated reduction in renal bloodfl ow com-pared with Schering 23390, a dopamine-1 receptorantagonist. Although Fenoldopam has been shown tobe a “reno-protective” agent in the setting of renalischemic injury during percutaneous coronary inter-vention (PCI),
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a protocol for prevention of radiographic contrast nephropathy during percutaneous coronary intervention effect of selective dopamine receptor agonist Fenoldopam
Catheterization and Cardiovascular Interventions, 2002Co-Authors: Annapoorna Kini, Cristina A Mitre, Mazullah Kamran, David Reich, Samin K SharmaAbstract:Radiographic contrast nephropathy (RCN), acute worsening of renal function due to contrast agents, can occur in 15%-40% of patients with baseline renal dysfunction undergoing percutaneous coronary intervention (PCI) and is associated with increased morbidity and in-hospital mortality. The purpose of this study was to evaluate whether the selective dopamine-1 (DA-1) receptor agonist Fenoldopam would be beneficial in patients with chronic renal insufficiency (CRI) undergoing PCI and also to design a protocol for prevention of RCN. We analyzed 150 consecutive patients with CRI [baseline serum creatinine (BSCr) +/- 1.5% mg] who underwent PCI and received Fenoldopam during and after the procedure, in addition to saline hydration. RCN, defined as > 25% increase of BSCr 48-72 hr after PCI, occurred in 4.7% (n = 7) of 150 PCI patients receiving Fenoldopam and 3.5% in diabetics (n = 85) vs. 6.1% in nondiabetics (n = 65; P = NS). No patients required dialysis. The observed 4.7% incidence of RCN with Fenoldopam was significantly lower than 18.8% incidence in the historical control group (P < 0.001). Our data suggest that Fenoldopam is a useful adjunct in the prevention of RCN during PCI, especially in diabetics.
Vandana Mathur - One of the best experts on this subject based on the ideXlab platform.
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differential effects between intravenous and targeted renal delivery of Fenoldopam on renal function and blood pressure in patients undergoing cardiac catheterization
American Journal of Cardiology, 2006Co-Authors: Paul S Teirstein, Vandana Mathur, Matthew J Price, Hooman Madyoon, Neil Sawhney, Donald S BaimAbstract:A randomized, controlled clinical trial demonstrated that intravenous (IV) Fenoldopam did not prevent further deterioration in renal function after contrast administration in patients with chronic renal insufficiency. This lack of effect may have been a consequence of the inability to administer an effective renal dose of IV Fenoldopam. This study sought to determine whether compared with IV administration, selective intrarenal (IR) Fenoldopam would increase local concentration, leading to a higher glomerular filtration rate (GFR), and, because of first-pass renal elimination, result in lower systemic drug levels and less decrease in systemic blood pressure (BP). A randomized, controlled, open-label, partial crossover design trial was conducted in which 33 patients who underwent coronary angiography were randomized in a 1:2 ratio to control or Fenoldopam (initially IV, then crossed over to IR through a bifurcated renal infusion catheter). Compared with IV Fenoldopam, IR administration was associated with a significantly higher GFR (73.7 ± 3.1 vs 62.6 ± 2.5 ml/min, p = 0.0007) and renal plasma flow (537.2 ± 34.0 vs 494.0 ± 35.5 ml/min, p
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Fenoldopam mesylate blocks reductions in renal plasma flow after radiocontrast dye infusion a pilot trial in the prevention of contrast nephropathy
American Heart Journal, 2002Co-Authors: J A Tumlin, Andrew Wang, P T Murray, Vandana MathurAbstract:Background Radiocontrast nephropathy (RCN) is a common source of acute renal failure in hospitalized patients and is associated with increased morbidity and mortality rates. Fenoldopam mesylate is a dopamine A1 receptor agonist that augments renal plasma flow (RPF) in patients with normotensive and hypertensive conditions. To determine whether Fenoldopam mesylate attenuates reductions in RPF after contrast infusion, we conducted a double-blind, randomized, placebo-controlled pilot trial of Fenoldopam mesylate in patients who underwent contrast angiography. Methods Fifty-one patients with chronic renal insufficiency (creatinine level, 2.0-5.0 mg/dL) who were undergoing contrast angiography were screened, and 45 patients were randomized to receive normal saline solution (1/2 NS) or 1/2 NS plus Fenoldopam mesylate at 0.1 μg/kg/min at lease 1 hour before infusion with contrast dye. Serum creatinine level was measured at baseline and at 24, 48, and 72 hours after angiography. The primary endpoint was change in RPF 1 hour after contrast infusion. The secondary endpoint was incidence of RCN, defined as a 0.5 mg/dL or a 25% rise in serum creatinine level at 48 hours. Results RPF at 1 hour after angiography was 15.8% above baseline in the Fenoldopam mesylate group compared with 33.2% below baseline in the 1/2 NS group (P <.05). The incidence rate of RCN at 48 hours was 41.0% in the 1/2 NS group versus 21% in the Fenoldopam mesylate group (P =.148). Among patients with diabetes, the incidence rate of RCN tended to be higher in the 1/2 NS group compared with the Fenoldopam mesylate group (64% vs 33%; P =.14). The peak serum creatinine level at 72 hours after contrast infusion was significantly higher at in the 1/2 NS group (creatinine level, 3.6 ± 1.0 mg/dL) compared with the Fenoldopam mesylate group (creatinine level, 2.8 ± 0.35 mg/dL; P <.05). RPF was significantly (P <.0001) reduced in patients with RCN compared with patients in whom RCN did not develop. Conclusion The results of this pilot trial suggest that Fenoldopam mesylate is a promising prophylactic agent for RCN and that larger multicenter trials should be conducted to prove its efficacy. (Am Heart J 2002;143:894-903.)
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the effects of Fenoldopam a selective dopamine receptor agonist on systemic and renal hemodynamics in normotensive subjects
Critical Care Medicine, 1999Co-Authors: Vandana Mathur, Suzanne K Swan, Lawrence J Lambrecht, Shakeel Anjum, Jere Fellmann, Dawn Mcguire, Murray Epstein, Robert R LutherAbstract:Objective: Acute renal fallure, frequently a consequence of renal vasoconstriction and subsequent renal Ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, Fenoldopam rapidly decreases blood pressure, Increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of Fenoldopam that Increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects. Design: Randomized, double-blind, placebo-controlled, crossover study. Setting: Clinical research unit. Patients: Fourteen normal male volunteers. Interventions: Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of Fenoldopam (0.03, 0.1, and 0.3 μg/kg/min) on both high-sodium and a low-sodium diet. Measurements and Main Results: Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 ± 148 vs. 576 ± 85 mL/min at 0.03 μg/kg/min; 777 ± 172 vs. 579 ± 80 mL/min at 0.1 μg/kg/min; and 784 ± 170 vs. 592 ± 165 mL/min at 0.3 μg/kg/min (p <.05 Fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 μg/kg/min), significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate. At 0.1 and 0.3 μg/kg/ min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the Fenoldopam group than in the placebo group: 62.5 ± 6.4 vs. 63.6 ± 2.6 mm Hg, respectively, at 0.3 μg/kg/min (p <.05). None of the effects of Fenoldopam were altered by volume status. Conclusions: Fenoldopam Increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate. These findings will be useful in designing future studies exploring the role of Fenoldopam in preventing or treating renal failure in patients who are not hypertensive.
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The effects of Fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in normotensive subjects
Critical Care Medicine, 1999Co-Authors: Vandana Mathur, Suzanne K Swan, Lawrence J Lambrecht, Shakeel Anjum, Jere Fellmann, Dawn Mcguire, Murray Epstein, Robert R LutherAbstract:Objective: Acute renal fallure, frequently a consequence of renal vasoconstriction and subsequent renal Ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, Fenoldopam rapidly decreases blood pressure, Increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of Fenoldopam that Increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects. Design: Randomized, double-blind, placebo-controlled, crossover study. Setting: Clinical research unit. Patients: Fourteen normal male volunteers. Interventions: Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of Fenoldopam (0.03, 0.1, and 0.3 μg/kg/min) on both high-sodium and a low-sodium diet. Measurements and Main Results: Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 ± 148 vs. 576 ± 85 mL/min at 0.03 μg/kg/min; 777 ± 172 vs. 579 ± 80 mL/min at 0.1 μg/kg/min; and 784 ± 170 vs. 592 ± 165 mL/min at 0.3 μg/kg/min (p
F Markos - One of the best experts on this subject based on the ideXlab platform.
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effects of Fenoldopam on renal blood flow and its function in a canine model of rhabdomyolysis
European Journal of Anaesthesiology, 2005Co-Authors: Clare Murray, F Markos, H M Snow, T B Corcoran, Nollaig A Parfrey, G D ShortenAbstract:Summary Background and objective: Our hypothesis was that Fenoldopam, a selective DA 1 agonist, would protect against rhabdomyolysis-induced renal injury. Methods: We studied the effects of intravenous Fenoldopam (0.1–1.0 μg kg −1 min −1 ) or saline on renal blood flow and function in 10 anaesthetized Labrador dogs in whom rhabdomyolysis and myoglobinuric acute renal failure had been induced by administration of glycerol 50% (10 mL kg −1 ) intramuscularly. Haemodynamic measurements including renal blood flow and derived parameters of renal function including creatinine clearance were recorded before and for the 30 min following glycerol injection, and during the 3 h following commencement of each infusion. Serum malondialdehyde concentrations were measured before and 15 min after glycerol intramuscularly, and 30 and 150 min after commencement of the infusion. Results: In the Fenoldopam group, creatinine clearance was less than placebo at 1 and 2 h after commencing the infusion (12.7 ± 11.5 versus 31.3 ± 9.9 mL min −1 , P = 0.04; 8.5 ± 5.3 versus 20.1 ± 7.4 mL min −1 , P = 0.03). A 140-fold increase in serum malondialdehyde concentration occurred in one dog (Fenoldopam group). Conclusion: Fenoldopam increased the severity of the renal injury in this canine model of myoglobinuric acute renal failure.
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effects of prophylactic Fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs
Critical Care Medicine, 2001Co-Authors: Michele Halpenny, F Markos, Henry M Snow, Patrick F Duggan, E Gaffney, Damian P Oconnell, G D ShortenAbstract:Objective: It was hypothesized that Fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of Fenoldopam (0.1 μg.kg -1 .min -1 ) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. Design: Prospective, randomized, controlled experiment. Setting: University-based animal laboratory and research unit. Subjects: Eight female beagle dogs. Interventions: Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of Fenoldopam or normal saline; b) during infusion of Fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of Fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. Measurements and Main Results: Administration of Fenoldopam (0.1 μg.kg -1 .min -1 ) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 ± 20 to 47 ± 6 mUmin and 0.26 ± 0.15 to 0.08 ± 0.05 mUmin, respectively) but not in the Fenoldopam group (75 ± 14 to 73 ± 17 mUmin and 0.3 ± 0.19 to 0.14 ± 0.05 mUmin, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 ± 0.4 to 1.8 ± 0.8 mL.kg -1 .min -1 and 1.7% ± 0.9% to 0.4% ± 0.2%, respectively) but not in the dogs that received Fenoldopam (3.0 ± 1.0 to 2.9 ± 0.5 mL.kg -1 .min -1 and 1.9% ± 1.1% to 1.7% ± 2.7%, respectively). Conclusions: Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that Fenoldopam may have a renoprotective effect in acute ischemic injury.
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the effects of Fenoldopam on renal blood flow and tubular function during aortic cross clamping in anaesthetized dogs
European Journal of Anaesthesiology, 2000Co-Authors: Michele Halpenny, F Markos, Henry M Snow, Patrick F Duggan, E Gaffney, Damian P Oconnell, G D ShortenAbstract:Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Fenoldopam, a selective dopamine agonist, may increase renal blood flow and decrease tubular oxygen consumption. The objective of this study was to quantify the effects of Fenoldopam (0.1 μg kg -1 min -1 ) on renal blood flow and renal tubular function in anaesthetized dogs that have undergone aortic cross clamping. Eight labrador dogs were selected to receive either saline or Fenoldopam (0.1 μg kg -1 min -1 ) intravenously. Arterial pressure, heart rate, renal blood flow, urinary output, fractional excretion of sodium, creatinine clearance and lithium clearance were measured (a) prior to infusions of saline or Fenoldopam (b) 1 h after commencing the infusion (c) during a 90-min period of infrarenal aortic cross-clamping with concurrent infusion of Fenoldopam or saline and (d) for 1 h after simultaneous aortic declamping and discontinuation of the infusions. There was no haemodynamic instability upon commencing the infusion of Fenoldopam (0.1 μg kg -1 min -1 ). Creatinine clearance (2.03 ± 0.5-2.45 ± 0.3 mL min -1 kg -1 (mean±SD)), urine output (0.23 ± 0.16-0.35 ± 0.23 mL min -1 (mean ± SD)), and fractional excretion of sodium (0.7 ± 0.52-1.3 ± 0.73% (mean ± SD)) increased (P < 0.05), following commencement of the Fenoldopam infusion. Fractional excretion of sodium (1.2 ± 0.7% (mean±SD)) and urine output (0.36 ± 0.21 mL min -1 (mean ± SD)) were maintained during the aortic cross-clamp period (P < 0.05). Renal blood flow increased when the Fenoldopam infusion was commenced (145 ± 43.3-161 ± 39.2 mL min -1 (mean ± SD)) and remained greater than baseline during the aortic cross-clamping period (152 ± 44 mL min -1 (mean±SD)), although these increases did not reach statistical significance. The most striking abnormalities observed by electron microscopy were marked disruption of the microvillus brush border in proximal tubules, vacuolation and separation of epithelial cells on basolateral infolds. The changes were similar in the two groups. In conclusion Fenoldopam (0.1 μg kg -1 min -1 ) may have renoprotective effects which persist during infrarenal aortic cross clamping.