Noémi Vida, Zoltán Varga, Antal Szabó-Biczók, Gábor Bari, Gyöngyvér Vigyikán, Ádám Hodoniczki, Ámos Gajda, Attila Rutai, László Juhász, Szabolcs Péter Tallósy, Sándor Túrkevi-Nagy, Anett Bársony, Nándor Öveges, Andrea Szabó, Mihály Boros, Gabriella Varga, Dániel Érces
{"title":"在24小时静脉-静脉体外膜氧合猪模型中，氧合期间给药甲烷可减轻急性肾损伤。","authors":"Noémi Vida, Zoltán Varga, Antal Szabó-Biczók, Gábor Bari, Gyöngyvér Vigyikán, Ádám Hodoniczki, Ámos Gajda, Attila Rutai, László Juhász, Szabolcs Péter Tallósy, Sándor Túrkevi-Nagy, Anett Bársony, Nándor Öveges, Andrea Szabó, Mihály Boros, Gabriella Varga, Dániel Érces","doi":"10.1097/SHK.0000000000002586","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Severe respiratory failure often requires veno-venous extracorporeal membrane oxygenation (v-v ECMO) treatment, a procedure frequently associated with acute kidney injury (AKI). Preclinical studies have demonstrated the anti-inflammatory properties of inhaled methane (CH4). This experimental protocol aimed to investigate whether CH4 gas administration could mitigate the development of AKI in a clinically relevant large animal model of v-v ECMO.</p><p><strong>Methods: </strong>Anesthetized miniature pigs were divided into three groups (n = 6 each). Following cannulation of the right femoral and internal jugular veins, v-v ECMO was initiated and maintained for 24 hours, followed by a 6-hour post-ECMO observation. The control group underwent cannulation without ECMO, while the v-v ECMO+CH4 group received a 2% CH4-air mixture via the oxygenator. Urine output was recorded, and kidney injury was assessed using plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) levels. Inflammatory activation was evaluated through plasma interleukin-1β (IL-1β) and interleukin-8 (IL-8) levels. Kidney tissue samples were analyzed for histopathological changes, xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) activities, and nitrite/nitrate (NOx) levels.</p><p><strong>Results: </strong>The CH4-treated group exhibited significantly higher post-ECMO renal arterial flow (244.7 ± 70 vs 96.3 ± 21 mL/min) and increased average urine output (5.75 ± 1.6 vs 3.25 ± 0.4 mL/h/kg) compared to the v-v ECMO group. CH4 administration reduced urine and plasma NGAL levels and demonstrated lower histological damage scores (0.8 ± 0.3 vs 3.3 ± 0.8). Furthermore, CH4 treatment decreased XOR and MPO activities and reduced inflammatory mediators, including IL-1β, IL-8, and NOx.</p><p><strong>Conclusion: </strong>CH4 admixture significantly mitigates inflammatory activation and renal injury associated with v-v ECMO. 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引用次数: 0
摘要
背景：严重呼吸衰竭通常需要静脉-静脉体外膜氧合（v-v ECMO）治疗，这一过程通常与急性肾损伤（AKI）相关。临床前研究已经证明了吸入甲烷（CH4）的抗炎特性。本实验方案旨在探讨CH4气体管理是否可以减轻临床相关的v-v ECMO大型动物模型中AKI的发展。方法：将麻醉后的小型猪分为3组，每组6头。在右股静脉和颈内静脉插管后，开始v-v ECMO并维持24小时，随后进行6小时ECMO后观察。对照组不进行ECMO插管，v-v ECMO+CH4组通过氧合器给予2% CH4-空气混合物。记录尿量，用血浆和尿液中性粒细胞明胶酶相关脂钙蛋白（NGAL）水平评估肾损伤。通过血浆白细胞介素-1β (IL-1β)和白细胞介素-8 （IL-8）水平评估炎症活化。分析肾脏组织样本的组织病理学变化、黄嘌呤氧化还原酶（XOR）和髓过氧化物酶（MPO）活性以及亚硝酸盐/硝酸盐（NOx）水平。结果：与v-v ECMO组相比，ch4治疗组ECMO后肾动脉血流明显增加（244.7±70 vs 96.3±21 mL/min），平均尿量增加（5.75±1.6 vs 3.25±0.4 mL/h/kg）。CH4可降低尿和血浆NGAL水平，组织学损伤评分降低（0.8±0.3 vs 3.3±0.8）。此外，CH4处理降低了XOR和MPO活性，减少了炎症介质，包括IL-1β、IL-8和NOx。结论：CH4可显著减轻v-v ECMO相关的炎症激活和肾损伤。这些发现提示CH4可作为减少v-v ECMO治疗肾脏并发症的有效辅助手段。
Methane administration during oxygenation mitigates acute kidney injury in a pig model of 24-hour veno-venous extracorporeal membrane oxygenation.
Background: Severe respiratory failure often requires veno-venous extracorporeal membrane oxygenation (v-v ECMO) treatment, a procedure frequently associated with acute kidney injury (AKI). Preclinical studies have demonstrated the anti-inflammatory properties of inhaled methane (CH4). This experimental protocol aimed to investigate whether CH4 gas administration could mitigate the development of AKI in a clinically relevant large animal model of v-v ECMO.
Methods: Anesthetized miniature pigs were divided into three groups (n = 6 each). Following cannulation of the right femoral and internal jugular veins, v-v ECMO was initiated and maintained for 24 hours, followed by a 6-hour post-ECMO observation. The control group underwent cannulation without ECMO, while the v-v ECMO+CH4 group received a 2% CH4-air mixture via the oxygenator. Urine output was recorded, and kidney injury was assessed using plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) levels. Inflammatory activation was evaluated through plasma interleukin-1β (IL-1β) and interleukin-8 (IL-8) levels. Kidney tissue samples were analyzed for histopathological changes, xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) activities, and nitrite/nitrate (NOx) levels.
Results: The CH4-treated group exhibited significantly higher post-ECMO renal arterial flow (244.7 ± 70 vs 96.3 ± 21 mL/min) and increased average urine output (5.75 ± 1.6 vs 3.25 ± 0.4 mL/h/kg) compared to the v-v ECMO group. CH4 administration reduced urine and plasma NGAL levels and demonstrated lower histological damage scores (0.8 ± 0.3 vs 3.3 ± 0.8). Furthermore, CH4 treatment decreased XOR and MPO activities and reduced inflammatory mediators, including IL-1β, IL-8, and NOx.
Conclusion: CH4 admixture significantly mitigates inflammatory activation and renal injury associated with v-v ECMO. These findings suggest that CH4 may serve as an effective adjunctive means to reduce renal complications of v-v ECMO therapy.
期刊介绍：
SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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