Microvascular Consequences of Methemoglobin Compared to Reduced Hemoglobin in the Microcirculation

IF 2 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2025-08-26 DOI:10.1111/micc.70022

Jacinda Martinez, Carlos Munoz, Daniela Lucas, Cynthia Muller, Krianthan Govender, Xiangming Gu, Andre F. Palmer, Pedro Cabrales

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引用次数: 0

Abstract

Objectives

The development of hemoglobin-based oxygen carriers (HBOCs) offers a promising alternative to traditional blood transfusions, addressing critical limitations such as the need for cold storage, blood type matching, and a short ex vivo shelf life. HBOCs mimic the oxygen-carrying function of red blood cells without the risk of transfusion-related complications. However, hemoglobin is prone to oxidation when freely circulating in the vasculature, resulting in methemoglobin formation. In this oxidized state, Hb does not transport oxygen, scavenges less nitric oxide, but it is more toxic. As continued research tries to develop effective HBOCs for use in emergency medicine, there needs to be an understanding of the microvascular and toxicological effects of the reduced and oxidized forms of Hb.

Materials and Methods

The study involved Golden Syrian Hamsters instrumented with a dorsal skin window chamber model to observe the acute effects resulting from a hypervolemic infusion (10% of the animal's blood volume) of human Hb [HbFe²⁺ (hHb)] or methemoglobin [HbFe³⁺ (met-hHb)] and lactated Ringer's solution as a volume control. Microhemodynamics, mean arterial pressure, heart rate, blood gases, and blood properties were measured.

Results

Mean arterial pressure (MAP) and heart rate (HR) were both altered; animals infused with hHb saw a significant increase in MAP and a decrease in HR, while animals infused with met-hHb saw a significant decrease in MAP and a decrease in HR. Infusion of hHb induced vasoconstriction and hypertension. However, infusion of met-hHb resulted in increased microvascular diameters compared to baseline, but a reduction in functional capillary density compared to baseline, alongside significant increases in inflammation, specifically in systemic and cardiac markers.

Conclusion

This study illuminates the complex impact of Hb oxidation on microvascular function and inflammation, pivotal to understanding the safety and efficacy of HBOC formulations. Future research should focus on strategies to regulate Hb oxidation to enhance therapeutic benefit and minimize detrimental effects in emergency medicine settings.

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与微循环中血红蛋白减少相比，高铁血红蛋白对微血管的影响

基于血红蛋白的氧载体（HBOCs）的发展为传统输血提供了一个有希望的替代方案，解决了诸如需要冷藏、血型匹配和较短的离体保质期等关键限制。hboc模拟红细胞的携氧功能，而没有输血相关并发症的风险。然而，当血红蛋白在血管中自由循环时，容易氧化，导致高铁血红蛋白的形成。在这种氧化状态下，Hb不运输氧气，清除较少的一氧化氮，但毒性更大。随着持续的研究试图开发用于急诊医学的有效血红蛋白，需要了解血红蛋白还原和氧化形式的微血管和毒理学作用。材料与方法采用背侧皮肤窗室模型，观察高容量输注（动物血容量的10%）人血红蛋白[HbFe2+ (hbb)]或高铁血红蛋白[HbFe3+ (met- hbb)]和乳酸林格氏液作为体积控制引起的急性效应。测量微血流动力学、平均动脉压、心率、血气和血液特性。结果平均动脉压（MAP）和心率（HR）均有改变；注射hbb的动物MAP显著升高，HR显著降低，而注射met- hbb的动物MAP显著降低，HR显著降低。hbb输注引起血管收缩和高血压。然而，与基线相比，输注met- hbb导致微血管直径增加，但与基线相比，功能性毛细血管密度降低，同时炎症显著增加，特别是全身和心脏标志物。结论本研究阐明了Hb氧化对微血管功能和炎症的复杂影响，对了解HBOC制剂的安全性和有效性至关重要。未来的研究应侧重于调节血红蛋白氧化的策略，以提高治疗效益，并尽量减少急诊医学环境中的有害影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.