Effects of the Kv7 voltage-activated potassium channel inhibitor linopirdine in rat models of haemorrhagic shock.
Effects of the Kv7 voltage-activated potassium channel inhibitor linopirdine in rat models of haemorrhagic shock.
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DOI：
10.1111/1440-1681.12958
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发表时间：
2018-04-27
影响因子：
2.9
通讯作者：
Majetschak M
中科院分区：
文献类型：
--
作者：
Nassoiy SP;Babu FS;LaPorte HM;Byron KL;Majetschak M
最近，我们证明 Kv7 电压激活钾通道抑制剂可减少短期失血性休克大鼠模型的液体复苏需求。本研究的目的是进一步描述 Kv7 通道阻滞剂利诺吡啶在临床相关时间段内各种严重失血性休克大鼠模型中的治疗潜力和副作用。在40%血容量出血之前（1或3 mg/kg）或之后（3 mg/kg）静脉注射利诺吡啶，不会影响不进行液体复苏的致死性出血模型中的血压和存活率。失血性休克后液体复苏开始时单次推注利诺吡啶 (3 mg/kg) 可暂时减少复苏 3.5 小时的自主呼吸动物的早期液体需求。当失血性休克后机械通气大鼠用生理盐水 (NS) 或补充利诺吡啶 (10、25 或 50 μg/mL) NS 复苏 4.5 小时时，利诺吡啶显着且剂量依赖性地分别使液体需求量减少 14%、45% 和 55%。利诺吡啶 (25/50 μg/mL) 降低了肺和结肠的湿/干重量比。根据血浆和组织匀浆中常规实验室参数和炎症标志物的测量，没有证据表明存在毒性或不良反应。我们的研究结果支持这样的观点，即补充复苏液中的利诺吡啶是减少失血性休克复苏过程中液体需求和组织水肿形成的安全有效的方法。
Recently, we demonstrated that Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements in short-term rat models of hemorrhagic shock. The aim of the present study was to further delineate the therapeutic potential and side effect profile of the Kv7 channel blocker linopirdine in various rat models of severe hemorrhagic shock over clinically relevant time periods. Intravenous administration of linopirdine, either before (1 or 3 mg/kg) or after (3 mg/kg) a 40% blood volume hemorrhage, did not affect blood pressure and survival in lethal hemorrhage models without fluid resuscitation. A single bolus of linopirdine (3 mg/kg) at the beginning of fluid resuscitation after hemorrhagic shock transiently reduced early fluid requirements in spontaneously breathing animals that were resuscitated for 3.5 hours. When mechanically ventilated rats were resuscitated after hemorrhagic shock with normal saline (NS) or with linopirdine-supplemented (10, 25 or 50 μg/mL) NS for 4.5 hours, linopirdine significantly and dose-dependently reduced fluid requirements by 14%, 45% and 55%, respectively. Lung and colon wet/dry weight ratios were reduced with linopirdine (25/50 μg/mL). There was no evidence for toxicity or adverse effects based on measurements of routine laboratory parameters and inflammation markers in plasma and tissue homogenates. Our findings support the concept that linopirdine-supplementation of resuscitation fluids is a safe and effective approach to reduce fluid requirements and tissue edema formation during resuscitation from hemorrhagic shock.
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DOI：
10.1097/ta.0b013e3181622bb6
发表时间：
2008-02-01
影响因子：
--
作者：
Madigan, Michael C.;Kemp, Clinton D.;Cotton, Bryan A.
通讯作者：
Cotton, Bryan A.
蛋白酶体抑制可延长大鼠致死性出血性休克期间的生存。
DOI：
10.1097/ta.0b013e31827d5db2
发表时间：
2013-02
期刊：
The journal of trauma and acute care surgery
影响因子：
--
作者：
Bach HH 4th;Laporte HM;Wong YM;Gamelli RL;Majetschak M
通讯作者：
Majetschak M
DOI：
10.1016/j.bbrc.2009.10.067
发表时间：
2009-12-25
影响因子：
3.1
作者：
Geng, Qing;Romero, Jacqueline;Saini, Vikas;Baker, Todd A.;Picken, Maria M.;Gamelli, Richard L.;Majetschak, Matthias
通讯作者：
Majetschak, Matthias
影响因子：
3.7
作者：
Chen X;Li W;Hiett SC;Obukhov AG
通讯作者：
Obukhov AG
影响因子：
3.7
作者：
Collier, Bryan;Dossett, Lesly;Morris, John
通讯作者：
Morris, John