Dilken Olcay, Ince Can, Kapucu Aysegul, Heeman Paul M, Ergin Bülent
Laboratory of Translational Intensive Care, Department of Intensive Care Adult, Erasmus MC, University Medical Center Rotterdam, Erasmus University, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
Department of Intensive Care, Faculty of Medicine, University of Istanbul-Cerrahpasa, Istanbul, Turkey.
Intensive Care Med Exp. 2023 May 1;11(1):25. doi: 10.1186/s40635-023-00509-3.
Perioperative acute kidney injury (AKI) caused by ischemia-reperfusion (IR) is a significant contributor to mortality and morbidity after major surgery. Furosemide is commonly used in postoperative patients to promote diuresis and reduce tissue edema. However, the effects of furosemide on renal microcirculation, oxygenation and function are poorly understood during perioperative period following ischemic insult. Herein, we investigated the effects of furosemide in rats subjected IR insult.
24 Wistar albino rats were divided into 4 groups, with 6 in each; Sham-operated Control (C), Control + Furosemide (C + F), ischemia/reperfusion (IR), and IR + F. After induction of anesthesia (BL), supra-aortic occlusion was applied to IR and IR + F groups for 45 min followed by ongoing reperfusion for 15 min (T1) and 2 h (T2). Furosemide infusion was initiated simultaneously in the intervention groups after ischemia. Renal blood flow (RBF), vascular resistance (RVR), oxygen delivery (DO) and consumption (VO), sodium reabsorption (TNa), oxygen utilization efficiency (VO/TNa), cortical (CμO) and medullary (MμO) microvascular oxygen pressures, urine output (UO) and creatinine clearance (Ccr) were measured. Biomarkers of inflammation, oxidative and nitrosative stress were measured and kidneys were harvested for histological analysis.
IR significantly decreased RBF, mainly by increasing RVR, which was exacerbated in the IR + F group at T2 (2198 ± 879 vs 4233 ± 2636 dyne/s/cm, p = 0.07). CμO (61.6 ± 6.8 vs 86 ± 6.6 mmHg) and MμO(51.1 ± 4.1 vs 68.7 ± 4.9 mmHg, p < 0.05) were both reduced after IR and did not improve by furosemide. Moreover, VO/TNaincreased in the IR + F group at T2 with respect to the IR group (IR: 3.3 ± 2 vs IR + F: 8.2 ± 10 p = 0.07) suggesting a possible deterioration of oxygen utilization. Ccr did not change, but plasma creatinine increased significantly in IR + F groups. Histopathology revealed widespread damage both in the cortex and medulla in IR, IR + F and C + F groups.
Renal microvascular oxygenation, renal function, renal vascular resistance, oxygen utilization and damage were not improved by furosemide administration after IR insult. Our study suggests that furosemide may cause additional structural and functional impairment to the kidney following ischemic injury and should be used with caution.
缺血再灌注（IR）引起的围手术期急性肾损伤（AKI）是大手术后死亡率和发病率的重要因素。呋塞米常用于术后患者以促进利尿并减轻组织水肿。然而，在缺血性损伤后的围手术期，呋塞米对肾微循环、氧合和功能的影响尚不清楚。在此，我们研究了呋塞米对遭受IR损伤的大鼠的影响。
将24只Wistar白化大鼠分为4组，每组6只；假手术对照组（C）、对照组+呋塞米（C+F）、缺血/再灌注（IR）组和IR+F组。麻醉诱导后（基线），对IR组和IR+F组进行主动脉上阻断45分钟，随后持续再灌注15分钟（T1）和2小时（T2）。缺血后干预组同时开始输注呋塞米。测量肾血流量（RBF）、血管阻力（RVR）、氧输送（DO）和消耗（VO）、钠重吸收（TNa）、氧利用效率（VO/TNa）、皮质（CμO）和髓质（MμO）微血管氧分压、尿量（UO）和肌酐清除率（Ccr）。测量炎症、氧化和亚硝化应激的生物标志物，并采集肾脏进行组织学分析。
IR主要通过增加RVR显著降低RBF，在T2时IR+F组这种情况加剧（2198±879 vs 4233±2636达因/秒/厘米，p=0.07）。IR后CμO（61.6±6.8 vs 86±6.6 mmHg）和MμO（51.1±4.1 vs 68.7±4.9 mmHg，p<0.05）均降低，且呋塞米未使其改善。此外，与IR组相比，IR+F组在T2时VO/TNa增加（IR：3.3±2 vs IR+F：8.2±10，p=0.07），提示氧利用可能恶化。Ccr未改变，但IR+F组血浆肌酐显著升高。组织病理学显示，IR组、IR+F组和C+F组的皮质和髓质均有广泛损伤。
IR损伤后给予呋塞米并不能改善肾微血管氧合、肾功能、肾血管阻力、氧利用和损伤。我们的研究表明，呋塞米可能在缺血性损伤后对肾脏造成额外的结构和功能损害，应谨慎使用。
