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 microcircu lation, oxygenation, morphology, and function were investigated in ane sthetized rats, and the contribution of coexisting perturbations to my oglobin nephrotoxicity were evaluated, Myoglobin infusion (3.3 mg/min) reduced outer medullary blood flow and P-O2, whereas renal blood flow and cortical P-O2 were unaffected, Myoglobin infusion (38 mg/100 g we ight over 45 min) induced renal failure associated with collecting duc t and medullary thick ascending limb dilation and casts, with focal tu bular damage, confined mainly to the superficial cortex, Preconditioni ng with indomethacin, 1-N-monomethyl arginine, and theophylline reduce d cortical superficial damage but enhanced injury within the inner str ipe of the outer meduila and in medullary rays, the zones of lowest O- 2 supply. In preconditioned animals, tubulorrhexis was primarily obser ved in collecting ducts transversing the inner stripe, and was remarka bly reminiscent of human descriptions (J. Oliver et al., J. Clin Inves t 1951;30:1307-1440), Deterioration in kidney function closely correla ted 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 da mage, medullary hypoxic injury, and tubular obstruction.