Microvascular stasis in course of sepsis might be a consequence of hemolysis
There are various studies demonstrating that hemolysis or the presence of cell-free hemoglobin and heme causes microvascular stasis (Figure 1). Buurman and his team of researchers already showed that acute hemolysis (with plasma levels of cfHb ~20–30 μmol/L) – induced by infusion of water or pre-lysed red blood cells – was associated with an impaired renal, hepatic and intestinal microvasculature.² They further showed that intraoperative hemolysis (with plasma levels of cfHb ~20 μmol/L) during major aortic surgery was associated with postoperative acute kidney injury.³ The offset times between occurring hemolysis and intestinal microvascular changes or renal microvascular changes were approximately 15–30 mins² respective 120 mins³. Moreover, Vinchi and co-workers could reduce liver damage in a mouse model of heme overload in wild-type mice compared to hemopexin-null mice.⁴ They concluded that hemopexin prevents from hemolysis-induced hepatic microvascular stasis.⁴ Belcher et al compared different treatments to induce hemolysis and heme overload (eg, infusion of water, hemoglobin or heme) in transgenic sickle mice and found a relationship between microvascular stasis and total plasma heme concentrations (with plasma levels of heme ~25–80 μmol/L).⁵ They further proved that intravascular hemolysis during sickle cell disease elicits microvascular stasis via Toll-like receptor 4 signaling.⁵ Further studies of the researchers around Belcher and Vercellotti showed inhibition of hemoglobin-induced microvascular stasis in transgenic sickle mice by hemopexin and haptoglobin supplementation,⁶ overexpression of hemopexin⁷ or overexpression of ferritin heavy chain ferrioxidase.⁸





中文翻译：

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微血管淤积和溶血：巧合还是因果关系？

败血症过程中的微血管淤积可能是溶血的结果。
有多项研究表明溶血或无细胞血红蛋白和血红素的存在会导致微血管淤积（图1）。Buurman和他的研究人员的研究小组已经表明，由输注水或预先溶解的红细胞引起的急性溶血（血浆水平为cfHb〜20–30μmol/ L）与肾，肝和肠道微脉管系统受损有关。²他们进一步表明，在主动脉手术期间术中溶血（血浆cfHb〜20μmol/ L）与术后急性肾损伤有关。³发生的溶血与肠道微血管变化或肾脏微血管变化之间的抵消时间分别为15分钟至30分钟²和120分钟³。而且，与不含血红素的小鼠相比，在野生型小鼠血红素超负荷的小鼠模型中，Vinchi及其同事可以减少肝脏损伤。⁴他们得出的结论是，血红蛋白可预防溶血引起的肝微血管淤积。⁴ Belcher等人比较了转基因镰刀小鼠中引起溶血和血红素超负荷（例如输注水，血红蛋白或血红素）的不同治疗方法，发现微血管滞留与血浆总血红素浓度（血浆血红素水平约为25-80）之间存在关联。 μmol/ L）。⁵他们进一步证明，镰状细胞病期间的血管内溶血可通过Toll样受体4信号传导引起微血管淤滞。⁵有关Belcher和Vercellotti的研究人员的进一步研究表明，通过添加血红蛋白和触珠蛋白，⁶血红蛋白^7的过表达或铁蛋白重链亚铁氧化酶的过高表达，可以抑制转基因镰刀中的血红蛋白诱导的微血管淤积。⁸