Effects of prophylactic fenoldopam infusion on renal blood flow and venal tubular function during acute hypovolemia in anesthetized dogs

Objective: It was hypothesized that fenoldopam mesylate, a selective dopami ne agonist, may preserve renal perfusion and decrease tubular oxygen consum ption during states of hypoperfusion, such as hypovolemic shock. The object ive of this study was to quantify the effects of fenoldopam (0.1 mug.kg(-1) .min(-1)) on renal blood flow, urine output, creatinine clearance, and sodi um 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 b lood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of fe noldopam or normal saline; b) during infusion of fenoldopam or normal salin e (1 hr); c) during a 90-min period of hypovolemia (induced by acute partia l exsanguination), with concurrent infusion of fenoldopam or normal saline; and d) during a l-hr period after retransfusing the dogs. Measurements and Main Results: Administration of fenoldopam (0.1 mug.kg(-1) .min(-1)) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p < .01) during th e hypovolemic period in the placebo group (72 <plus/minus> 20 to 47 +/- 6 m L/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in t he fenoldopam group (75 +/- 14 to 73 +/- 17 mL/min and 0.3 +/- 0.19 to 0.14 +/- 0.05 mL/min, respectively). Creatinine clearance and fractional excret ion of sodium decreased significantly from baseline (p < .01) in the placeb o group during the hypovolemic period (3.0 <plus/minus> 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 h ypovolemia 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.