Wilken Silvana N, Rodrigues Diego V Santos, Price Colin, Jacobs Julia, Nelson Jack, Walker Patrick F, Morrison Jonathan J
Department of Surgery, Mayo Clinic, 200 1 Street, Rochester, MN 55905, USA.
Division of Vascular and Endovascular Surgery, Mayo Clinic, 200 1 Street, Rochester, MN 55905, USA.
Surg Pract Sci. 2025 May 17;21:100286. doi: 10.1016/j.sipas.2025.100286. eCollection 2025 Jun.
Acute mesenteric ischemia (AMI) is a surgical emergency requiring prompt revascularization with resection of unsalvageable bowel. Despite successful revascularization, ongoing organ damage can persist from ischemia-reperfusion injury (IRI) and there is a need for adjunct therapies to ameliorate this ongoing insult.
Sprague-Dawley rats ( = 36) were divided into five groups: control, heparin (HEP), HEP + verapamil (VER), HEP + valproic acid (VPA), HEP+VER+VPA. The animals were subjected to 45 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Upon reperfusion, therapies were administered. Plasma samples were collected before occlusion and at end-of-study for intestinal fatty acid binding protein (I-FABP) and pro-inflammatory cytokines. The full length of the small intestine was collected, stained with H&E and scored according to the Park/Chiu score for intestinal ischemia damage.
Twenty-three of 36 rats survived 4 h of reperfusion and there was no difference in survival between the groups. I-FABP levels was significantly lower in HEP+VER vs. control (3.8 ± 1.5 vs. 6.18 ± 1.0ng/ml; = 0.0040). IL-1beta, IL-6 and TNF-alpha showed the lowest mean values in the HEP+VER group compared to all groups. The histological analysis revealed the lowest score of intestinal damage in the HEP+VER group, however, the difference to control was not significant.
Administering heparin and verapamil at the time of revascularization may mitigate intestinal IRI without causing detrimental systemic effects. Further studies in large animal models and in the setting of local administration are needed to investigate the potential of this approach.
急性肠系膜缺血（AMI）是一种外科急症，需要迅速进行血管再通并切除无法挽救的肠段。尽管血管再通成功，但缺血再灌注损伤（IRI）仍可导致持续的器官损伤，因此需要辅助治疗来减轻这种持续的损伤。
将36只Sprague-Dawley大鼠分为五组：对照组、肝素（HEP）组、HEP+维拉帕米（VER）组、HEP+丙戊酸（VPA）组、HEP+VER+VPA组。对动物进行45分钟的肠系膜上动脉闭塞，随后再灌注4小时。再灌注时给予相应治疗。在闭塞前和研究结束时采集血浆样本，检测肠道脂肪酸结合蛋白（I-FABP）和促炎细胞因子。收集小肠全长，用苏木精-伊红染色，并根据Park/Chiu评分对肠道缺血损伤进行评分。
36只大鼠中有23只存活至再灌注4小时，各组间生存率无差异。HEP+VER组的I-FABP水平显著低于对照组（3.8±1.5 vs. 6.18±1.0ng/ml；P = 0.0040）。与所有组相比，HEP+VER组的IL-1β、IL-6和TNF-α均值最低。组织学分析显示HEP+VER组肠道损伤评分最低，但与对照组的差异不显著。
血管再通时给予肝素和维拉帕米可能减轻肠道IRI，且不会引起有害的全身效应。需要在大型动物模型和局部给药的情况下进行进一步研究，以探讨这种方法的潜力。
