Validation of intraosseous delivery of valproic acid in a swine model of polytrauma.
Validation of intraosseous delivery of valproic acid in a swine model of polytrauma.
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DOI：
10.1136/tsaco-2021-000683
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发表时间：
2021
影响因子：
2
通讯作者：
Alam HB
中科院分区：
文献类型：
--
作者：
Biesterveld BE;O'Connell R;Kemp MT;Wakam GK;Williams AM;Pai MP;Alam HB
在无法获得静脉通路的紧急情况下，可能需要骨内 (IO) 药物输送。丙戊酸 (VPA) 是一种组蛋白脱乙酰酶抑制剂，此前已被证明可以提高致死性多发伤临床前模型的生存率。在本研究中，我们试图比较静脉注射和 IO 递送的 VPA 的血清水平，并分析 IO 递送的 VPA 的效果。猪遭受40%血容量出血、脑损伤、股骨骨折、直肌挤压伤和肝脏撕裂伤。休克1小时后，动物随机（n=3/组）接受生理盐水复苏（对照）、生理盐水+静脉VPA 150 mg/kg（静脉组）或生理盐水+IO VPA 150 mg/kg（IO组）。评估各组之间的 VPA 血清水平，并对 IO 组和对照组的心脏、肺和肝脏样本进行蛋白质组学分析。开始输注后 1、3、5 和 7 小时，静脉内和 IO 血清 VPA 水平相似 (p>0.05)。 IO 递送的 VPA 在心脏、肺和肝脏中引起显着的蛋白质组学变化，其中在肺中最为明显。受影响的生物过程包括炎症、新陈代谢以及转录和翻译机制。到实验结束时，对照组的存活率为 0%，静脉注射组和 IO 组的存活率为 100%（p<0.05）。 IO 递送的 VPA 并不劣于静脉注射，并且在无法进行静脉注射的紧急情况下是一种可行的选择。不适用（动物研究）。
Intraosseous (IO) drug delivery may be necessary in emergency situations when intravenous access is unattainable. Valproic acid (VPA) is a histone deacetylase inhibitor that has previously been shown to improve survival in preclinical models of lethal polytrauma. In this study, we sought to compare serum levels of intravenously and IO-delivered VPA, and to analyze the effect of IO-delivered VPA. Swine were subjected to 40% blood volume hemorrhage, brain injury, femur fracture, rectus crush injury and liver laceration. After 1 hour of shock, animals were randomized (n=3/group) to receive normal saline resuscitation (control), normal saline+intravenous VPA 150 mg/kg (intravenous group) or normal saline +IO VPA 150 mg/kg (IO group). Serum levels of VPA were assessed between groups, and proteomics analyses were performed on IO and control groups on heart, lung and liver samples. Intravenous and IO serum VPA levels were similar at 1, 3, 5 and 7 hours after starting the infusion (p>0.05). IO-delivered VPA induced significant proteomics changes in the heart, lung and liver, which were most pronounced in the lung. Biologic processes affected included inflammation, metabolism and transcriptional & translational machinery. The control group had 0% survival, and the intravenous and IO group both had 100% survival to the end of the experiment (p<0.05). IO-delivered VPA is noninferior to intravenous administration and is a viable option in emergent situations when intravenous access is unattainable. Not applicable (animal study).
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DOI：
10.1097/ta.0000000000001765
发表时间：
2018-03
期刊：
The journal of trauma and acute care surgery
影响因子：
--
作者：
Nikolian VC;Dennahy IS;Higgins GA;Williams AM;Weykamp M;Georgoff PE;Eidy H;Ghandour MH;Chang P;Alam HB
通讯作者：
Alam HB
影响因子：
3.4
作者：
Georgoff, Patrick E.;Nikolian, Vahagn C.;Alam, Hasan B.
通讯作者：
Alam, Hasan B.
影响因子：
--
作者：
Holloway, Cpt Monica M;Jurina, Cpt Shannan L;Johnson, Don
通讯作者：
Johnson, Don
影响因子：
37.8
作者：
Link, Mark S.;Berkow, Lauren C.;Donnino, Michael W.
通讯作者：
Donnino, Michael W.
影响因子：
6.5
作者：
Mody, Purav;Brown, Siobhan P.;Idris, Ahamed H.
通讯作者：
Idris, Ahamed H.