Effects of tempol on renal medullary tissue hypoxia in an ovine model of Gram-negative septic acute kidney injury.

Renal arterial infusion of tempol (RAT) at the onset of Gram-negative sepsis can prevent sepsis-induced medullary tissue hypoxia and acute kidney injury (AKI). However, it is not known whether treatment with tempol at a clinically relevant time point of sepsis is similarly effective. Thus, we examined whether tempol can reverse renal medullary tissue hypoxia after ovine Gram-negative septic AKI. Following right unilateral nephrectomy, the left kidney was instrumented with a renal arterial catheter and oxygen-sensing fibre-optic probes into the renal medulla. After 23 h of Escherichia coli infusion, conscious sheep were fluid resuscitated with Hartmann's solution (30 mL/kg over 0.5 h) and randomized to intravenous tempol (IVT; n = 7) at 30 mg/kg/h, RAT (3 mg/kg/h; n = 6) or vehicle (n = 5) from 24 to 31 h of sepsis. At 31 h, E. coli infusion ceased, and sheep received ceftriaxone (1 g) and were allowed a 48 h recovery period. At 23 h of E. coli infusion, septic sheep developed a 2.2 ± 0.8-fold increase in plasma creatinine and a 57% ± 6% decrease in urine output, and the renal medulla was ischaemic and hypoxic. Neither RAT nor IVT attenuated the sepsis-induced renal medullary tissue hypoxia during the 7 h intervention period. Renal medullary tissue partial pressure of O