Risks of Impaired Organ Protection with Inhibiting Transient Receptor Potential Vanilloid 1.
Risks of Impaired Organ Protection with Inhibiting Transient Receptor Potential Vanilloid 1.
复制标题
抑制瞬时受体电位香草醛导致器官保护受损的风险 1。
DOI：
10.1097/aln.0000000000002293
复制
发表时间：
2018
期刊：
影响因子：
8.8
通讯作者：
Qian,Jinqiao
中科院分区：
文献类型：
--
作者：
Wu,Yu;Gross,EricR;Qian,Jinqiao
我们最近怀着极大的兴趣阅读了Garami等人的手稿，说明瞬时受体电位香草酸1（TRPV 1）拮抗剂AMG 517和ABT-102如何预防麻醉诱导的体温过低，同时降低啮齿动物术后痛觉过敏的阿片类药物需求。这些临床前数据表明，TRPV 1拮抗剂可用作术中和术后镇痛的阿片类药物保留方式，同时还提供高热以抵消麻醉诱导的体温过低。这一发现非常新颖，可能会导致开发新的阿片类药物用于围手术期。然而，如果作者能评论我们在手术中使用TRPV 1拮抗剂的一些潜在缺点以及克服这些障碍的潜在策略，我们将受益匪浅。例如，静脉注射TRPV 1拮抗剂也可能阻断器官保护的内源性机制。重要的是要认识到，与野生型（WT）TRPV 1小鼠相比，未处理的TRPV 1敲除小鼠或使用分离的心脏模型经受缺血-再灌注损伤的用TRPV 1抑制剂处理的小鼠产生受损的功能恢复。2此外，在醋酸脱氧皮质酮（DOCA）-盐高血压模型中，与对照组相比，C57 BL/6小鼠中TRPV 1基因的消融加重了肾损伤。
With great interest we recently read the manuscript by Garami et al., 1 illustrating how the transient receptor potential vanilloid 1 (TRPV1) antagonists, AMG 517 and ABT-102, prevent anesthesia-induced hypothermia and simultaneously decrease opioid requirements for postoperative hyperalgesia in rodents. These preclinical data suggest that TRPV1 antagonists may be useful as opioid-sparing modalities for analgesia intraoperatively and postoperatively while also providing hyperthermia to pharmacologically counteract anesthetic-induced hypothermia. This finding is pretty novel and may lead the way to developing new opioid sparing drugs to be used perioperatively. However, it would be of benefit if the authors may comment on some of the potential shortcomings we see of using TRPV1 antagonists during surgery and potential strategies to overcome these barriers we outline below.For example, intravenous administration of TRPV1 antagonists may also block endogenous mechanisms of organ protection. It is important to recognize that untreated TRPV1 knockout mice or mice treated with a TRPV1 inhibitor subjected to ischemia-reperfusion injury using an isolated heart model produce impaired functional recovery compared to wild type (WT) TRPV1 mice. 2 Further, in a deoxycorticosterone acetate (DOCA)-salt hypertension model, ablation of TRPV1 gene in the C57BL/6 mice exacerbates renal damage compared to