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Aim: Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti‐inflammatory drug, tempol, may modify these responses. Methods: Following unilateral nephrectomy, we inserted renal arterial catheters and laser‐Doppler/oxygen‐sensing probes in the renal cortex and medulla. Noanesthetized sheep were administered intravenous (IV) Escherichia coli and, at sepsis onset, IV tempol (IVT; 30 mg kg−1 h−1), renal arterial tempol (RAT; 3 mg kg−1 h−1), or vehicle. Results: Septic sheep receiving vehicle developed renal medullary hypoperfusion (76 ± 16% decrease in perfusion), hypoxia (70 ± 13% decrease in oxygenation), and AKI (87 ± 8% decrease in creatinine clearance) with similar changes during IVT. However, RAT preserved medullary perfusion (1072 ± 307 to 1005 ± 271 units), oxygenation (46 ± 8 to 43 ± 6 mmHg), and creatinine clearance (61 ± 10 to 66 ± 20 mL min−1). Plasma, renal medullary, and cortical tissue malonaldehyde and medullary 3‐nitrotyrosine decreased significantly with sepsis but were unaffected by IVT or RAT. Consistent with decreased oxidative/nitrosative stress markers, cortical and medullary nuclear factor‐erythroid‐related factor‐2 increased significantly and were unaffected by IVT or RAT. However, RAT prevented sepsis‐induced overexpression of cortical tissue tumor necrosis factor alpha (TNF‐α; 51 ± 16% decrease; p = 0.003) and medullary Thr‐495 phosphorylation of endothelial nitric oxide synthase (eNOS; 63 ± 18% decrease; p = 0.015). Conclusions: In ovine Gram‐negative sepsis, renal arterial infusion of tempol prevented renal medullary hypoperfusion and hypoxia and AKI and decreased TNF‐α expression and uncoupling of eNOS. However, it did not affect markers of oxidative/nitrosative stress, which were significantly decreased by Gram‐negative sepsis. [ABSTRACT FROM AUTHOR]

Aim: Renal tissue hypoxia during cardiopulmonary bypass could contribute to the pathophysiology of acute kidney injury. We tested whether renal tissue hypoxia can be alleviated during cardiopulmonary bypass by the combined increase in target pump flow and mean arterial pressure. Methods: Cardiopulmonary bypass was established in eight instrumented sheep under isoflurane anaesthesia, at a target continuous pump flow of 80 mL·kg−1 min−1 and mean arterial pressure of 65 mmHg. We then tested the effects of simultaneously increasing target pump flow to 104 mL·kg−1 min−1 and mean arterial pressure to 80 mmHg with metaraminol (total dose 0.25‐3.75 mg). We also tested the effects of transitioning from continuous flow to partially pulsatile flow (pulse pressure ~15 mmHg). Results: Compared with conscious sheep, at the lower target pump flow and mean arterial pressure, cardiopulmonary bypass was accompanied by reduced renal blood flow (6.8 ± 1.2 to 1.95 ± 0.76 mL·min−1 kg−1) and renal oxygen delivery (0.91 ± 0.18 to 0.24 ± 0.11 mL·O2 min−1 kg−1). There were profound reductions in cortical oxygen tension (PO2) (33 ± 13 to 6 ± 6 mmHg) and medullary PO2 (31 ± 12 to 8 ± 8 mmHg). Increasing target pump flow and mean arterial pressure increased renal blood flow (to 2.6 ± 1.0 mL·min−1 kg−1) and renal oxygen delivery (to 0.32 ± 0.13 mL·O2 min−1kg−1) and returned cortical PO2 to 58 ± 60 mmHg and medullary PO2 to 28 ± 16 mmHg; levels similar to those of conscious sheep. Partially pulsatile pump flow had no significant effects on renal perfusion or oxygenation. Conclusions: Renal hypoxia during experimental CPB can be corrected by increasing target pump flow and mean arterial pressure within a clinically feasible range. [ABSTRACT FROM AUTHOR]

Aim: Blood transfusion may improve renal oxygenation during cardiopulmonary bypass (CPB). In an ovine model of experimental CPB, we tested whether increasing blood haemoglobin concentration [Hb] from ~7 g dL−1 to ~9 g dL−1 improves renal tissue oxygenation. Methods: Ten sheep were studied while conscious, under stable isoflurane anaesthesia, and during 3 hours of CPB. In a randomized cross‐over design, 5 sheep commenced bypass at a high target [Hb], achieved by adding 600 mL donor blood to the priming solution. After 90 minutes of CPB, PlasmaLyte® was added to the blood reservoir to achieve low target [Hb]. For the other 5 sheep, no blood was added to the prime, but after 90 minutes of CPB, 800‐900 mL of donor blood was given to achieve a high target [Hb]. Results: Overall, CPB was associated with marked reductions in renal oxygen delivery (−50 ± 12%, mean ± 95% confidence interval) and medullary tissue oxygen tension (PO2, −54 ± 29%). Renal fractional oxygen extraction was 17 ± 10% less during CPB at high [Hb] than low [Hb] (P =.04). Nevertheless, no increase in tissue PO2 in either the renal medulla (0 ± 6 mmHg change, P >.99) or cortex (−19 ± 13 mmHg change, P =.08) was detected with high [Hb]. Conclusions: In experimental CPB blood transfusion to increase Hb concentration from ~7 g dL−1 to ~9 g dL−1 did not improve renal cortical or medullary tissue PO2 even though it decreased whole kidney oxygen extraction. [ABSTRACT FROM AUTHOR]