Myoglobinuric acute renal failure in the rat: a role for medullary hypoperfusion, hypoxia, and tubular obstruction.
Myoglobin induces renal injury by mechanisms that remain incompletely defined. In this study, the effects of myoglobin upon renal microcirculation, oxygenation, morphology, and function were investigated in anesthetized rats, and the contribution of coexisting perturbations to myoglobin nephrotoxicity were evaluated. Myoglobin infusion (3.3 mg/min) reduced outer medullary blood flow and Po2, whereas renal blood flow and cortical Po2 were unaffected. Myoglobin infusion (38 mg/100 g weight over 45 min) induced renal failure associated with collecting duct and medullary thick ascending limb dilation and casts, with focal tubular damage, confined mainly to the superficial cortex. Preconditioning with indomethacin, I-N-monomethyl arginine, and theophylline reduced cortical superficial damage but enhanced injury within the inner stripe of the outer medulla and in medullary rays, the zones of lowest O2 supply. In preconditioned animals, tubulorrhexis was primarily observed in collecting ducts transversing the inner stripe, and was remarkably reminiscent of human descriptions (J. Oliver et al., J Clin Invest 1951; 30: 1307-1440). Deterioration in kidney function closely correlated with morphologic features of both tubular obstruction and necrosis. In conclusion, medullary vasoconstriction and intrarenal hypoxia may play a role in myoglobin-induced renal failure. The deterioration in kidney function appears to reflect the combined effects of cortical damage, medullary hypoxic injury, and tubular obstruction.
Heyman
S N
SN
Department of Medicine, Hadassah Hospital, Mt. Scopus, Jerusalem, Israel.
Rosen
S
S
Fuchs
S
S
Epstein
F H
FH
Brezis
M
M
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D006801:Humans; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000098:blood supply* / Q000378:metabolism; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology / Q000503:physiopathology; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008833:Microcirculation; D009211:Myoglobin / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction
D009211:Myoglobin