Department of Neurosurgery, University of New Mexico School of Medicine, Albuquerque, NM, USA.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Adv Exp Med Biol. 2018;1072:39-43. doi: 10.1007/978-3-319-91287-5_7.
Traumatic brain injury (TBI) is frequently accompanied by hemorrhagic shock (HS) which significantly worsens morbidity and mortality. Existing resuscitation fluids (RF) for volume expansion inadequately mitigate impaired microvascular cerebral blood flow (mvCBF) and hypoxia after TBI/HS. We hypothesized that nanomolar quantities of drag reducing polymers in resuscitation fluid (DRP-RF), would improve mvCBF by rheological modulation of hemodynamics.
TBI was induced in rats by fluid percussion (1.5 atm, 50 ms) followed by controlled hemorrhage to a mean arterial pressure (MAP) = 40 mmHg. DRP-RF or lactated Ringer (LR-RF) was infused to MAP of 60 mmHg for 1 h (pre-hospital), followed by blood re-infusion to a MAP = 70 mmHg (hospital). Temperature, MAP, blood gases and electrolytes were monitored. In vivo 2-photon laser scanning microscopy was used to monitor microvascular blood flow, hypoxia (NADH) and necrosis (i.v. propidium iodide) for 5 h after TBI/HS followed by MRI for CBF and lesion volume.
TBI/HS compromised brain microvascular flow leading to capillary microthrombosis, tissue hypoxia and neuronal necrosis. DRP-RF compared to LR-RF reduced microthrombosis, restored collapsed capillary flow and improved mvCBF (82 ± 9.7% vs. 62 ± 9.7%, respectively, p < 0.05, n = 10). DRP-RF vs LR-RF decreased tissue hypoxia (77 ± 8.2% vs. 60 ± 10.5%, p < 0.05), and neuronal necrosis (21 ± 7.2% vs. 36 ± 7.3%, respectively, p < 0.05). MRI showed reduced lesion volumes with DRP-RF.
DRP-RF effectively restores mvCBF, reduces hypoxia and protects neurons compared to conventional volume expansion with LR-RF after TBI/HS.
颅脑损伤(TBI)常伴有失血性休克(HS),这显著增加了发病率和死亡率。现有的复苏液(RF)在TBI/HS 后不能充分缓解受损的微血管脑血流(mvCBF)和缺氧。我们假设,复苏液中的纳米级数量的减阻聚合物(DRP-RF)将通过血流动力学的流变调节来改善 mvCBF。
通过液体冲击(1.5 atm,50 ms)诱导大鼠 TBI,然后将平均动脉压(MAP)降至 40 mmHg 进行控制性出血。DRP-RF 或乳酸林格氏液(LR-RF)输注至 MAP 为 60 mmHg 持续 1 小时(院前),然后再将 MAP 输血至 70 mmHg(院内)。监测体温、MAP、血气和电解质。在 TBI/HS 后进行 5 小时的活体双光子激光扫描显微镜监测微血管血流、缺氧(NADH)和坏死(静脉注射碘化丙啶),然后进行 MRI 监测 CBF 和病变体积。
TBI/HS 损害脑微血管血流,导致毛细血管微血栓形成、组织缺氧和神经元坏死。与 LR-RF 相比,DRP-RF 减少了微血栓形成,恢复了塌陷的毛细血管血流,改善了 mvCBF(分别为 82 ± 9.7% vs. 62 ± 9.7%,p < 0.05,n = 10)。DRP-RF 与 LR-RF 相比降低了组织缺氧(77 ± 8.2% vs. 60 ± 10.5%,p < 0.05)和神经元坏死(21 ± 7.2% vs. 36 ± 7.3%,分别,p < 0.05)。MRI 显示 DRP-RF 可减少病变体积。
与传统的 LR-RF 容量扩张相比,DRP-RF 可有效恢复 TBI/HS 后 mvCBF,减少缺氧并保护神经元。