Norepinephrine exacerbates renal medullary hypoxia in experimental septic acute kidney injury. Here we examined whether dexmedetomidine, an α2-adrenergic agonist, can restore vasopressor responsiveness, decrease the requirement for norepinephrine and attenuate medullary hypoxia in ovine gram-negative sepsis. Sheep were instrumented with pulmonary and renal artery flow probes, and laser Doppler and oxygen-sensing probes in the renal cortex and medulla. Conscious sheep received an infusion of live Escherichia coli for 30 hours. Eight sheep in each group were randomized to receive norepinephrine, norepinephrine with dexmedetomidine, dexmedetomidine alone or saline vehicle, from 24-30 hours of sepsis. Sepsis significantly reduced the average mean arterial pressure (84 to 67 mmHg), average renal medullary perfusion (1250 to 730 perfusion units), average medullary tissue pO₂ (40 to 21 mmHg) and creatinine clearance (2.50 to 0.78 mL/Kg/min). Norepinephrine restored baseline mean arterial pressure (to 83 mmHg) but worsened medullary hypoperfusion (to 330 perfusion units) and medullary hypoxia (to 9 mmHg). Dexmedetomidine (0.5 μg/kg/h) co-administration significantly reduced the norepinephrine dose (0.8 to 0.4 μg/kg/min) required to restore baseline mean arterial pressure, attenuated medullary hypoperfusion (to 606 perfusion units), decreased medullary tissue hypoxia (to 29 mmHg), and progressively increased creatinine clearance (to 1.8 mL/Kg/min). Compared with vehicle time-control, dexmedetomidine given alone significantly prevented the temporal reduction in mean arterial pressure, but had no significant effects on medullary perfusion and oxygenation or creatinine clearance. Thus, in experimental septic acute kidney injury, dexmedetomidine reduced norepinephrine requirements, attenuated its adverse effects on the renal medulla, and maintained renal function.

去甲肾上腺素在实验性脓毒性急性肾损伤中加重了肾髓质缺氧。在这里，我们检查了右旋美托咪定（一种α2-肾上腺素能激动剂）是否可以恢复血管升压药反应性，降低去甲肾上腺素的需求并减轻绵羊革兰氏阴性脓毒症的髓质缺氧。用肺和肾动脉血流探头，以及在肾皮质和髓质中用激光多普勒和氧气感应探头对绵羊进行检测。有意识的绵羊接受了活大肠杆菌的注入30小时。从败血症的24-30小时起，将每组中的八只绵羊随机接受去甲肾上腺素，去甲肾上腺素与右美托咪定，单独的右美托咪定或生理盐水载体。脓毒症显着降低了平均平均动脉压（84至67 mmHg），平均肾髓质灌注（1250至730灌注单位），平均髓质组织pO ₂（40至21 mmHg）和肌酐清除率（2.50至0.78 mL / Kg / min）。去甲肾上腺素恢复了基线平均动脉压（至83 mmHg），但髓质低灌注（至330灌注单位）和髓质缺氧（至9 mmHg）恶化。右美托咪定（0.5μg/ kg / h）共同给药可显着降低恢复基线平均动脉压所需的去甲肾上腺素剂量（0.8至0.4μg/ kg / min），减弱的髓质灌注不足（至606个灌注单位），减少的髓质组织缺氧（至29 mmHg），并逐渐增加肌酐清除率（至1.8 mL / Kg / min）。与溶媒时间控制相比，单独给予右美托咪定可以显着阻止平均动脉压的暂时降低，但对髓质灌注和充氧或肌酐清除率没有明显影响。因此，