Protective effects of hemoglobin vesicles on intestinal ischemia-reperfusion injury in a rat model of thoracic aortic occlusion

IF 2.3 Q3 Medicine

JVS-vascular science Pub Date : 2026-01-01 Epub Date: 2026-03-12 DOI:10.1016/j.jvssci.2026.100418

Keisuke Tsuruta PhD, MD , Hidetada Fukushima PhD, MD , Hiromi Sakai PhD

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Abstract

Intestinal ischemia-reperfusion (I/R) injury is a major complication of aortic occlusion during resuscitative thoracotomy or resuscitative endovascular balloon occlusion of the aorta. We investigated whether targeted intra-arterial delivery of hemoglobin vesicles (HbVs) attenuates intestinal I/R injury in a rat thoracic aortic cross-clamping model. Male Wistar rats underwent 60 minutes of thoracic aortic occlusion followed by 60 minutes of reperfusion. Animals received intra-arterial HbV (1.25 mL/kg every 10 minutes; n = 5) or saline (n = 5) via the femoral artery; sham animals (n = 3) underwent instrumentation only. Compared with saline controls, HbV-treated rats demonstrated higher postreperfusion systolic blood pressure (56 ± 4 mm Hg vs 34 ± 8 mm Hg; P = .002) and lower plasma lactate levels (2.7 ± 0.4 mmol/L vs 7.5 ± 0.4 mmol/L; P < .001). Intestinal injury was significantly attenuated in the HbV group, with lower Chiu scores (median 2.0 vs 4.0; P = .018), reduced terminal deoxynucleotidyl transferase dUTP nick end labeling-positive area fraction (P = .003), and decreased inducible nitric oxide synthase-positive area fraction (P = .006). Targeted intra-arterial HbV administration significantly reduced early intestinal I/R injury in this exploratory proof-of-concept model and may represent a promising adjunctive oxygen-carrying strategy to protect distal organs during prolonged aortic occlusion.

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血红蛋白囊泡对大鼠胸主动脉闭塞模型肠缺血再灌注损伤的保护作用

肠缺血再灌注（I/R）损伤是复苏开胸术或复苏血管内球囊主动脉闭塞术中主动脉闭塞的主要并发症。在大鼠胸主动脉交叉夹持模型中，我们研究了靶向动脉内输送血红蛋白囊泡（HbVs）是否能减轻肠I/R损伤。雄性Wistar大鼠进行60分钟的胸主动脉阻断，然后进行60分钟的再灌注。经股动脉注射HbV（每10分钟注射1.25 mL/kg, n = 5）或生理盐水（n = 5）；假动物（n = 3）仅接受仪器检查。与生理盐水对照组相比，hbv治疗大鼠表现出更高的灌注后收缩压（56±4 mm Hg vs 34±8 mm Hg; P = 0.002）和更低的血浆乳酸水平（2.7±0.4 mmol/L vs 7.5±0.4 mmol/L; P < 0.001）。HbV组肠道损伤明显减轻，Chiu评分较低（中位数2.0 vs 4.0, P = 0.018），末端脱氧核苷酸转移酶dUTP缺口末端标记阳性面积分数降低（P = 0.003），诱导型一氧化氮合酶阳性面积分数降低（P = 0.006）。在这个探索性概念验证模型中，靶向动脉内HbV给药显著减少了早期肠道I/R损伤，可能代表了一种有前途的辅助载氧策略，可以在长时间主动脉闭塞期间保护远端器官。

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