Department of Plastic and Hand Surgery, University Hospital Rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany; Division of Plastic, Reconstructive and Aesthetic Surgery, Ospedale Regionale di Lugano (ORL), Sede Italiano, Ente Ospedaliero Cantonale (EOC), Via Capelli, 6962 Viganello-Lugano, Lugano, Switzerland.
Department of Plastic and Hand Surgery, University Hospital Rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany.
J Plast Reconstr Aesthet Surg. 2019 Apr;72(4):590-599. doi: 10.1016/j.bjps.2019.01.003. Epub 2019 Jan 9.
It has been shown that pre- and postconditioning of ischemically challenged tissue with erythropoietin (EPO) is able to reduce necrosis in a dose-dependent manner. The aim of this study was to determine the tissue-protective effects of different EPO dosages and administration regimes. Three groups of six C57Bl/6-mice each were analyzed: (1) pre- and postconditioning with initial high doses of EPO (starting at 2500 I.U./kg bw i.p.) followed by low doses of EPO (125 I.U./kg bw i.p.) (EPO-high-dose); (2) pre- and postconditioning with low doses of EPO (125 I.U./kg bw i.p.) (EPO-low-dose); and (3) untreated control group. Randomly perfused musculocutaneous flaps were mounted on dorsal skinfold chambers undergoing acute persistent ischemia and developing ∼50% necrosis without treatment. Intravital epifluorescence microscopy was performed at days 1, 3, 5, 7, and 10 after surgery, assessing flap necrosis, microcirculation, and angiogenesis. The hematocrit was measured at days 0, 3, 7, and 10. Only the EPO-low-dose regimen was associated with a significant reduction of necrosis when compared to untreated controls. EPO-low-dose showed a higher increase in both arteriolar diameter and velocity, thereby resulting in a significantly increased arteriolar blood flow and a hence higher functional capillary density (FCD) of the critically perfused zone. EPO-induced angiogenesis was significantly increased in EPO-low-dose at days 7 and 10. Only EPO-high-dose reached a significant hematocrit increase by day 10. Tissue pre- and postconditioning with low doses of EPO protects the critically perfused musculocutaneous tissue by maintaining capillary perfusion because of increased arteriolar blood flow mediated by nitric oxide (NO) expression.
已经表明，用促红细胞生成素 (EPO) 对缺血性挑战组织进行预处理和后处理能够以剂量依赖的方式减少坏死。本研究的目的是确定不同 EPO 剂量和给药方案的组织保护作用。分析了三组每组六只 C57Bl/6 小鼠：(1) 用初始高剂量 EPO（起始剂量为 2500 I.U./kg bw i.p.）进行预处理和后处理，然后用低剂量 EPO（125 I.U./kg bw i.p.）进行预处理和后处理（EPO-高剂量）；(2) 用低剂量 EPO（125 I.U./kg bw i.p.）进行预处理和后处理（EPO-低剂量）；(3) 未治疗的对照组。随机灌注的皮瓣安装在背部皮肤褶皱室上，这些皮瓣经历急性持续性缺血，在未治疗的情况下发展为约 50%的坏死。手术后第 1、3、5、7 和 10 天进行活体荧光显微镜检查，评估皮瓣坏死、微循环和血管生成。在第 0、3、7 和 10 天测量血细胞比容。只有 EPO-低剂量方案与未治疗的对照组相比，可显著减少坏死。EPO-低剂量方案表现出动脉直径和速度的显著增加，从而导致动脉血流显著增加，因此临界灌注区的功能性毛细血管密度 (FCD) 更高。EPO-低剂量方案在第 7 和 10 天观察到 EPO 诱导的血管生成显著增加。只有 EPO-高剂量方案在第 10 天达到显著的血细胞比容增加。低剂量 EPO 的组织预处理和后处理通过增加一氧化氮 (NO) 表达介导的动脉血流来维持毛细血管灌注，从而保护临界灌注的肌肉皮肤组织。
