Munoz Carlos, Aletti Federico, Govender Krianthan, Cabrales Pedro, Kistler Erik B
Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States.
Department of Anesthesiology and Critical Care, University of California, San Diego, La Jolla, CA, United States.
Front Med (Lausanne). 2020 Oct 27;7:585638. doi: 10.3389/fmed.2020.585638. eCollection 2020.
Microcirculatory preservation is essential for patient recovery from hemorrhagic shock. In hemorrhagic shock, microcirculatory flow and pressure are greatly reduced, creating an oxygen debt that may eventually become irreversible. During shock, tissues become hypoxic, cellular respiration turns to anaerobic metabolism, and the microcirculation rapidly begins to fail. This condition requires immediate fluid resuscitation to promote tissue reperfusion. The choice of fluid for resuscitation is whole blood; however, this may not be readily available and, on a larger scale, may be globally insufficient. Thus, extensive research on viable alternatives to blood has been undertaken in an effort to develop a clinically deployable blood substitute. This has not, as of yet, achieved fruition, in part due to an incomplete understanding of the complexities of the function of blood in the microcirculation. Hemodynamic resuscitation is acknowledged to be contingent on a number of factors other than volume expansion. The circulation of whole blood is carefully regulated to optimize oxygen delivery to the tissues shear stress modulation through blood viscosity, inherent oxygen-carrying capacity, cell-free layer variation, and myogenic response, among other variables. Although plasma expanders can address a number of these issues, hemoglobin-based oxygen carriers (HBOCs) introduce a method of replenishing the intrinsic oxygen-carrying capacity of blood. There continue to be a number of issues related to HBOCs, but recent advances in the next-generation HBOCs show promise in the preservation of microcirculatory function and limiting toxicities. The development of HBOCs is now focused on viscosity and the degree of microvascular shear stress achieved in order to optimize vasoactive and oxygen delivery responses by leveraging the restoration and maintenance of physiological responses to blood flow in the microcirculation. Blood substitutes with higher viscous properties tend to improve oxygen delivery compared to those with lower viscosities. This review details current concepts in blood substitutes, particularly as they relate to trauma/hemorrhagic shock, with a specific focus on their complex interactions in the microcirculation.
微循环的保护对于出血性休克患者的恢复至关重要。在出血性休克中，微循环血流和压力大幅降低，产生氧债，最终可能变得不可逆转。休克期间，组织会缺氧，细胞呼吸转向无氧代谢，微循环迅速开始衰竭。这种情况需要立即进行液体复苏以促进组织再灌注。复苏所用的液体选择是全血；然而，全血可能不易获得，而且从更大范围来看，全球可能供应不足。因此，人们对血液的可行替代品进行了广泛研究，以期开发出一种可临床应用的血液替代品。截至目前，这一努力尚未取得成果，部分原因是对血液在微循环中功能的复杂性认识不足。血流动力学复苏被认为取决于除扩容之外的许多因素。全血的循环受到精心调节，以通过血液粘度、固有携氧能力、无细胞层变化和肌源性反应等多种变量来优化向组织的氧输送和剪切应力调节。尽管血浆扩容剂可以解决其中一些问题，但基于血红蛋白的氧载体（HBOCs）提供了一种补充血液固有携氧能力的方法。与HBOCs相关的问题仍然存在，但新一代HBOCs的最新进展在保护微循环功能和限制毒性方面显示出前景。目前HBOCs的开发重点在于粘度以及所实现的微血管剪切应力程度，以便通过利用微循环中对血流的生理反应的恢复和维持来优化血管活性和氧输送反应。与低粘度的血液替代品相比，具有较高粘性特性的血液替代品往往能改善氧输送。本综述详细介绍了血液替代品的当前概念，特别是与创伤/出血性休克相关的概念，并特别关注它们在微循环中的复杂相互作用。
