Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-10T17:31:05.062Z Has data issue: false hasContentIssue false

Effects of fenoldopam on renal blood flow and its function in a canine model of rhabdomyolysis

Published online by Cambridge University Press:  11 July 2005

C. Murray
Affiliation:
Cork University Hospital and University College Cork, Departments of Anaesthesia and Intensive Care Medicine, Ireland
F. Markos
Affiliation:
University College Cork, Department of Physiology, Cork, Ireland
H. M. Snow
Affiliation:
University College Cork, Department of Physiology, Cork, Ireland
T. Corcoran
Affiliation:
Cork University Hospital and University College Cork, Departments of Anaesthesia and Intensive Care Medicine, Ireland
N. Parfrey
Affiliation:
Cork University Hospital, Department of Histopathology, Cork, Ireland
G. D. Shorten
Affiliation:
Cork University Hospital and University College Cork, Departments of Anaesthesia and Intensive Care Medicine, Ireland
Get access

Extract

Summary

Background and objective: Our hypothesis was that fenoldopam, a selective DA1 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.

Type
Original Article
Copyright
© 2003 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Slater MS, Mullins RJ. Rhabdomyolysis and myoglobinuric renal failure in trauma and surgical patients: A review. J Am Coll Surg 1998; 186: 693716.Google Scholar
Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine 1982; 61: 141152.Google Scholar
Zager RA. Rhabdomyolysis and myohemoglobinuric acute renal failure. Kidney Int 1996; 49: 314326.Google Scholar
Paller MS. Hemoglobin- and myoglobin-induced acute renal failure in rats: role of iron in nephrotoxicity. Am J Physiol 1988; 255: F539F544.Google Scholar
Shah SV, Walker PD. Evidence suggesting a role for hydroxyl radical in glycerol-induced acute renal failure. Am J Physiol 1988; 255: F438F443.Google Scholar
Maree A, Peer G, Schwartz D, et al. Role of nitric oxide in glycerol-induced acute renal failure in rats. Nephrol Dial Transplant 1994; 9 (Suppl 4): 7881.Google Scholar
Valdivielso JM, Lopez-Novoa JM, Eleno N, Perez-Barriocanal F. Role of glomerular nitric oxide in glycerol-induced acute renal failure. Can J Physiol Pharmacol 2000; 78: 476482.Google Scholar
Gomez-Garre DN, Lopez-Farre A, Eleno N, Lopez-Novoa JM. Comparative effects of dopexamine and dopamine on glycerol-induced acute renal failure in rats. Ren Fail 1996; 18: 5968.Google Scholar
Shimazu T, Yoshioka T, Nakata Y, et al. Fluid resuscitation and systemic complications in crush syndrome: 14 Hanshin-Awaji earthquake patients. J Trauma 1997; 42: 641646.Google Scholar
Hahn RA, Wardell JR, Sarau HM, Ridley PT. Characterization of the peripheral and central effects of SK&F 52623, a novel dopamine receptor agonist. J Pharmacol Exp Ther 1982; 223: 305311.Google Scholar
Mathur VS, Swan SK, Lambrecht LJ, et al. The effects of fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in normotensive subjects. Crit Care Med 1999; 27: 18321837.Google Scholar
Dlewati A, Lokhwandala F. Dose–response analysis of the effects of fenoldopam, a dopamine-1 receptor agonist, on renal function. Drug Dev Res 1991; 22: 5968.Google Scholar
Brooks DP, Goldstein R, Koster PF, et al. Effect of fenoldopam in dogs with spontaneous renal insufficiency. Eur J Pharmacol 1990; 184: 195199.Google Scholar
Halpenny M, Markos F, Snow HM, et al. The effects of fenoldopam on renal blood flow and tubular function during aortic cross-clamping in anaesthetized dogs. Eur J Anaesthesiol 2000; 17: 491498.Google Scholar
Halpenny M, Rushe C, Breen P, Cunningham AJ, Boucher-Hayes D, Shorten GD. The effects of fenoldopam on renal function in patients undergoing elective aortic surgery. Eur J Anaesthesiol 2002; 19: 3239.Google Scholar
Thiel G, Wilson DR, Arce ML, Oken DE. Glycerol induced hemoglobinuric acute renal failure in the rat. II. The experimental model, predisposing factors, and pathophysiologic features. Nephron 1967; 4: 276297.Google Scholar
Better OS, Stein JH. Early management of shock and prophylaxis of acute renal failure in traumatic rhabdomyolysis. N Engl J Med 1990; 322: 825829.Google Scholar
Bull AW, Marnett LJ. Determination of malondialdehyde by ion-pairing high-performance liquid chromatography. Anal Biochem 1985; 149: 284290.Google Scholar
Csallany AS, Der Guan M, Manwaring JD, Addis P. Free malondialdehyde determination in tissues by high-performance liquid chromatography. Anal Biochem 1984; 142: 277283.Google Scholar
Zager RA, Burkhart K. Myoglobin toxicity in proximal human kidney cells: Roles of Fe, Ca2+, H2O2, and terminal mitochondrial electron transport. Kidney Int 1997; 51: 728738.Google Scholar
Moore K, Roberts LJ II. Measurement of lipid peroxidation. Free Radic Res 1998; 28: 659671.Google Scholar
Kien ND, Moore PG, Jaffe RS. Cardiovascular function during induced hypotension by fenoldopam or sodium nitroprusside in anesthetized dogs. Anesth Analg 1992; 74: 7278.Google Scholar
Ketterer B. Glutathione S-transferases and prevention of cellular free radical damage. Free Radic Res 1998; 28: 647658.Google Scholar
Baez S, Segura-Aguilar J, Widersten M, Johansson A, Mannervik B. Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes. Biochem J 1997; 324: 2528.Google Scholar
Boppana VK, Heineman FC, Lynn RK, Randolph WC, Ziemniak JA. Determination of fenoldopam (SK&F 82526) and its metabolites in human plasma and urine by high-performance liquid chromatography with electrochemical detection. J Chromatogr 1984; 28: 463474.Google Scholar
Southard JH, Marsh DC, McAnulty JF, Belzer FO. Oxygen-derived free radical damage in organ preservation: activity of superoxide dismutase and xanthine oxidase. Surgery 1987; 101: 566570.Google Scholar
Gluck Z, Jossen L, Weidmann P, Gnadinger MP, Peheim E. Cardiovascular and renal profile of acute peripheral dopamine-1-receptor agonism with fenoldopam. Hypertension 1987; 10: 4354.Google Scholar
Stote RM, Dubb JW, Familiar RG, Erb BB, Alexander F. A new oral renal vasodilator, fenoldopam. Clin Pharmacol Ther 1983; 34: 309315.Google Scholar
Allison NL, Dubb JW, Ziemniak JA, Alexander F, Stote RM. The effect of fenoldopam, a dopaminergic agonist, on renal hemodynamics. Clin Pharmacol Ther 1987; 41: 282288.Google Scholar
Baker SL, Dodds EC. Obstruction of the renal tubules during the excretion of haemoglobin. Br J Exp Pathol 1925; 6: 247260.Google Scholar
Perri GC, Gerini P. Uraemia in the rabbit after injection of crystalline myoglobin. Br J Exp Pathol 1952; 33: 440444.Google Scholar