Effects of prophylactic fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs.
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 microg x kg(-1) x 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.


METHODS
Prospective, randomized, controlled experiment.


METHODS
University-based animal laboratory and research unit.


METHODS
Eight female beagle dogs.


METHODS
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.


RESULTS
Administration of fenoldopam (0.1 microg x kg(-1) x 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 mL/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in the 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 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 x kg(-1) x 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 x kg(-1) x 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.
Halpenny
M
M
Department of Anesthesia and Intensive Care Medicine, Mercy Hospital and University College Cork, Wilton, Cork, Ireland.
Markos
F
F
Snow
H M
HM
Duggan
P F
PF
Gaffney
E
E
O'Connell
D P
DP
Shorten
G D
GD
D058186:Acute Kidney Injury / Q000188:drug therapy*; D000704:Analysis of Variance; D000818:Animals; D003404:Creatinine / Q000097:blood; D004285:Dogs; D005260:Female; D018818:Fenoldopam / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D020896:Hypovolemia / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007684:Kidney Tubules / Q000187:drug effects* / Q000648:ultrastructure; D012079:Renal Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D003404:Creatinine; D018818:Fenoldopam