William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
Life Sci. 2012 Oct 29;91(17-18):852-9. doi: 10.1016/j.lfs.2012.08.036. Epub 2012 Sep 13.
Lumbricus terrestris (earthworm) erythrocruorin (LtEc) is a naturally occurring extracellular hemoglobin (Hb) with high molecular weight (3.6MDa), low autoxidation rate, and limited nitric oxide (NO) dioxygenation activity. These properties make LtEc a potential candidate for use as red blood cell (RBC) substitute, i.e. Hb-based oxygen carrier (HBOC). Previous studies have shown that small amounts of LtEc can be safely transfused into mice, rats, and hamsters without eliciting major side effects. Therefore, this study was designed to understand oxygen (O(2)) transport to tissues and systemic/microvascular hemodynamics induced by LtEc during anemic conditions.
Hamsters fitted with dorsal window chambers were hemodiluted to 18% hematocrit (Hct) using 6g/dL dextran 70kDa (Dex70). Hemodilution was then continued to 11% Hct using 10g/dL LtEc, 6g/dL Dex70 or 10g/dL human serum albumin (HSA). Blood pressure, heart rate, blood gas parameters, microvascular hemodynamics, microvascular blood flow, functional capillary density (FCD), intravascular pO(2) and perivascular pO(2) were studied.
LtEc maintained blood pressure without inducing vasoconstriction while increasing microvascular perfusion and FCD relative to Dex70 and HSA. LtEc increased blood O(2) carrying capacity and maintained systemic and microvascular parameters without decreasing arteriolar diameter or increasing vascular resistance with during extreme anemia. LtEc increased O(2) delivery compared to conventional plasma expanders.
LtEc or synthetic molecules that replicate the characteristics of LtEc could be effective O(2) carriers with potential to be used in transfusion medicine to prevent tissue anoxia resulting from severe anemia.
蚯蚓血晶蛋白（LtEc）是一种天然存在的细胞外血红蛋白（Hb），具有高分子量（3.6MDa）、低自氧化率和有限的一氧化氮（NO）双加氧酶活性。这些特性使 LtEc 成为一种有潜力的红细胞（RBC）替代品，即血红蛋白基氧载体（HBOC）。先前的研究表明，少量 LtEc 可以安全地输注到小鼠、大鼠和仓鼠体内，而不会引起主要的副作用。因此，本研究旨在了解 LtEc 在贫血状态下向组织输送氧气（O(2)）和引起全身/微血管血液动力学变化的情况。
在背部窗口室中安装的仓鼠通过使用 6g/dL 葡聚糖 70kDa（Dex70）将血细胞比容（Hct）稀释至 18%。然后继续使用 10g/dL LtEc、6g/dL Dex70 或 10g/dL 人血清白蛋白（HSA）将血细胞比容稀释至 11%。研究了血压、心率、血气参数、微血管血液动力学、微血管血流、功能性毛细血管密度（FCD）、血管内 pO(2)和血管周 pO(2)。
与 Dex70 和 HSA 相比，LtEc 维持血压而不引起血管收缩，同时增加微血管灌注和 FCD。LtEc 增加血液 O(2)携载能力，并在不降低小动脉直径或增加血管阻力的情况下维持全身和微血管参数，在极度贫血时不降低组织缺氧。与常规血浆扩张剂相比，LtEc 增加了 O(2)的输送。
LtEc 或复制 LtEc 特征的合成分子可能是有效的 O(2)载体，有潜力在输血医学中用于预防严重贫血引起的组织缺氧。
