Shallie Philemon, Carpenter Nathan, Anamthathmakula Prashanth, Kinsey Danielle, Moncure Michael, Honaryar Houman, Ghazali Hanieh Sadat, Niroobakhsh Zahra, Rodriguez Juan, Simpkins Cuthbert O
Department of Surgery, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
Department of Surgery, University Health Truman Medical Center, Kansas City, MO 64108, USA.
Biomedicines. 2024 Dec 12;12(12):2824. doi: 10.3390/biomedicines12122824.
: Exsanguination is a leading cause of preventable death in military and civilian settings due to extensive blood loss and hemorrhagic shock, which trigger systemic effects such as impaired tissue perfusion, hypoxia, inflammation, and multi-organ dysfunction. Standard resuscitation restores blood volume but fails to address critical aspects of hemorrhagic shock, including inflammation, coagulopathy, and reperfusion injury. To address these limitations, novel phospholipid nanoparticle (PNP)-based resuscitative fluids, VBI-S and VBI-1, were developed to modulate nitric oxide (NO) levels, improving hemodynamic stability, tissue oxygenation, and reducing inflammatory injury. This study assessed the potential of novel phospholipid nanoparticle fluids, VBI-S and VBI-1, as resuscitative agents for severe hemorrhagic shock by evaluating their ability to regulate nitric oxide, restore blood pressure, and mitigate ischemia-reperfusion injury. This study involved two phases with Sprague Dawley rats (n = 6 per group). Phase one, lasting 4 h, included four groups: blood, Ringer's lactate, VBI-S, and VBI-1. Phase two, lasting 12 h, comprised sham, blood, and VBI-1 groups. Under anesthesia, one femoral artery was catheterized for blood pressure monitoring, and blood withdrawal from the other induced apnea. Reanimation was performed using an intra-arterial infusion of shed blood, Ringer's lactate, VBI-S, or VBI-1. Tissue samples were analyzed histologically and for oxidative DNA damage via immunofluorescence. Chemiluminescence and rheology assessed nitric oxide interactions and viscosity. Data were analyzed using ANOVA. : VBI-1 and shed blood increased mean arterial pressure (MAP) from <10 mmHg to survivable levels sustained for 12 h, with VBI-1 showing significantly higher MAP at 3-4 h. Rats treated with Ringer's lactate died within 30 min. Histology revealed reduced organ damage in VBI-1-treated rats compared to shed blood. Immunohistochemistry indicated significantly less oxidative DNA damage ( < 0.001) in VBI-1-treated rats. VBI-1 exhibited superior viscosity and nitric oxide binding. VBI-1 demonstrates strong potential as a resuscitative fluid, offering blood pressure restoration, reduced oxidative damage, and enhanced tissue perfusion, with significant implications for use in resource-limited and pre-hospital settings.
因大量失血和失血性休克导致的放血是军事和民用环境中可预防死亡的主要原因，失血性休克会引发全身性影响，如组织灌注受损、缺氧、炎症和多器官功能障碍。标准复苏可恢复血容量，但无法解决失血性休克的关键问题，包括炎症、凝血病和再灌注损伤。为解决这些局限性，研发了新型基于磷脂纳米颗粒（PNP）的复苏液VBI-S和VBI-1，以调节一氧化氮（NO）水平，改善血流动力学稳定性、组织氧合并减少炎症损伤。本研究通过评估新型磷脂纳米颗粒液VBI-S和VBI-1调节一氧化氮、恢复血压和减轻缺血再灌注损伤的能力，来评估其作为严重失血性休克复苏剂的潜力。本研究涉及两个阶段，使用Sprague Dawley大鼠（每组n = 6）。第一阶段持续4小时，包括四组：血液、乳酸林格液、VBI-S和VBI-1。第二阶段持续12小时，包括假手术组、血液组和VBI-1组。在麻醉状态下，一根股动脉插入导管用于监测血压，从另一根股动脉放血诱导呼吸暂停。使用动脉内输注自体血、乳酸林格液、VBI-S或VBI-1进行复苏。对组织样本进行组织学分析，并通过免疫荧光分析氧化DNA损伤。通过化学发光和流变学评估一氧化氮相互作用和粘度。数据采用方差分析进行分析。VBI-1和自体血将平均动脉压（MAP）从<10 mmHg提高到可存活水平并维持12小时，VBI-1在3至4小时时MAP显著更高。用乳酸林格液治疗的大鼠在30分钟内死亡。组织学显示，与自体血相比，VBI-1治疗的大鼠器官损伤减轻。免疫组织化学表明，VBI-1治疗的大鼠氧化DNA损伤明显更少（<0.001）。VBI-1表现出优异的粘度和一氧化氮结合能力。VBI-1作为一种复苏液显示出强大的潜力，可恢复血压、减少氧化损伤并增强组织灌注，对在资源有限和院前环境中的应用具有重要意义。
