Genét Gustav Folmer, Bentzer Peter, Hansen Morten Bagge, Ostrowski Sisse Rye, Johansson Pär Ingemar
From the Section for Transfusion Medicine (G.F.G., M.B.H., S.R.O., P.I.J.), Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Anesthesia and Intensive Care (P.B.), Helsingborg Hospital, Helsingborg and Lund University, Lund, Sweden; and Department of Surgery (P.I.J.), Center for Translational Injury Research, CeTIR, University of Texas Medical School at Houston, Texas.
J Trauma Acute Care Surg. 2018 Jan;84(1):89-96. doi: 10.1097/TA.0000000000001708.
Traumatic brain injury causes a disruption of the vascular endothelial glycocalyx layer that is associated with an overactivation of the sympathoadrenal system. We hypothesized that early and unselective beta-blockade with propranolol alone or in combination with the alfa2-agonist clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma.
We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal motor function.
We found no difference in brain water content (mean ± SD) between propranolol (80.8 ± 0.3%; 95% confidence interval [CI], 80.7-81.0) and vehicle (81.1 ± 0.6%; 95% CI, 80.8-81.4) (p = 0.668) or between propranolol/clonidine (80.8 ± 0.3%; 95% CI, 80.7-81.0) and vehicle (p = 0.555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels.
This study does not provide any support for unselective beta-blockade with propranolol or the combination of propranolol and the alfa2-agonist clonidine on brain water content. The novel finding of an increase in plasma concentrations of epinephrine and syndecan-1 after propranolol treatment in traumatic brain injury is of unclear significance and should be investigated further.
创伤性脑损伤会导致血管内皮糖萼层破坏，这与交感肾上腺系统的过度激活有关。我们假设，在创伤后24小时，单独使用普萘洛尔或与α2激动剂可乐定联合进行早期非选择性β受体阻滞，会减轻脑水肿、血脑屏障通透性和糖萼破坏。
我们将53只成年雄性Sprague-Dawley大鼠进行侧方液体冲击性脑损伤，并随机给予普萘洛尔（n = 16）、普萘洛尔 + 可乐定（n = 16）、赋形剂（n = 16）或假手术（n = 5），持续24小时。主要结局是24小时时的脑含水量。次要结局是血脑屏障通透性和syndecan-1（糖萼破坏）的血浆水平、细胞损伤（组蛋白复合DNA片段）、肾上腺素、去甲肾上腺素和动物运动功能。
我们发现普萘洛尔组（80.8 ± 0.3%；95%置信区间[CI]，80.7 - 81.0）与赋形剂组（81.1 ± 0.6%；95% CI，80.8 - 81.4）之间的脑含水量无差异（p = 0.668），普萘洛尔/可乐定组（80.8 ± 0.3%；95% CI，80.7 - 81.0）与赋形剂组之间也无差异（p = 0.555）。我们发现普萘洛尔和普萘洛尔/可乐定对血脑屏障通透性和动物运动评分没有影响。出乎意料的是，普萘洛尔和普萘洛尔/可乐定导致肾上腺素和syndecan-1水平升高。
本研究不支持使用普萘洛尔进行非选择性β受体阻滞或普萘洛尔与α2激动剂可乐定联合使用对脑含水量的影响。创伤性脑损伤患者使用普萘洛尔治疗后肾上腺素和syndecan-1血浆浓度升高这一新发现的意义尚不清楚，应进一步研究。
