METHODS: Sixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8).
RESULTS: Empagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes.
CONCLUSIONS: In a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.
方法:对16只健康的美利诺母羊进行外科手术,以测量平均动脉压,心输出量,肾血流量,肾皮质和髓质灌注,和氧合。经过5天的恢复期,脓毒症是通过缓慢和连续静脉输注活大肠杆菌诱导的。二十三小时后,绵羊随机接受静脉推注0.2mg/kg依帕列净(n=8)或液体匹配载体(n=8).
结果:Empagliflozin治疗并没有显著减少肾髓质灌注不足或缺氧,改善肾功能,或诱导组织学变化。干预期间,依帕列净组的肾皮质氧合为47.6±5.9mmHg,而安慰剂组为40.6±8.2mmHg(P=0.16)。empagliflozin的肾脏髓质氧合为28.0±18.5mmHg,而25.7±16.3mmHg(P=0.82)。Empagliflozin治疗并没有导致肾血流量的显著组间差异,肾功能,或肾组织病理学改变。
结论:在脓毒症AKI的大型哺乳动物模型中,单剂量的依帕列净并不能改善肾脏微循环灌注,氧合,肾功能,或组织病理学。