Castro C, Ortiz D, Palmer A F, Cabrales P
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA -
Minerva Anestesiol. 2014 May;80(5):537-46. Epub 2013 Nov 26.
Compared to blood transfusion, plasma expanders (PEs) are more cost effective, have a longer shelf-life, and elicit a milder immune response. High molecular weight (MW) dextrans preserve microvascular function during extreme hemodilution. Dextrans, however, evokes negative hemostatic effects, including red blood cell (RBC) aggregation and reduce platelet adhesion, that limit their clinical use. Therefore, polymerization of human serum albumin (HSA) presents a simple strategy to increase HSA's molecular size.
This study was designed to test the hypothesis that polymerized HSA (PolyHSA) biophysical properties improves systemic and microvascular hemodynamics when used as a PE under anemic conditions. The study was implemented using the hamster window chamber model. Animals were first hemodiluted to 18% hematocrit (Hct) using 6% dextran 70 kDa and then to 11% Hct using either 10% PolyHSA, 10% unpolymerized HSA, or 6% dextran 70 kDa. Systemic and microvascular hemodynamics, including cardiac output (CO), mean arterial blood pressure (MAP), functional capillary density (FCD), microvascular perfusion, and oxygen tension were measured.
Posthemodilution, PolyHSA improved MAP, CO, and oxygen delivery compared to HSA and dextran. Additionally, PolyHSA improved microvascular function in terms of blood flow and FCD. Although oxygen carrying capacity is limited at 11% Hct, tissue pO2 and oxygen delivery were higher for PolyHSA compared to HSA and dextran.
PolyHSA during extreme anemia supported systemic and microvascular hemodynamics by increasing plasma viscosity without increasing vascular resistance. These findings can aid to design of studies to understand the role of the PE biophysical properties in clinical scenarios.
与输血相比,血浆扩容剂(PEs)更具成本效益,保质期更长,且引发的免疫反应更温和。高分子量(MW)右旋糖酐在极度血液稀释期间可维持微血管功能。然而,右旋糖酐会产生负面的止血作用,包括红细胞(RBC)聚集和降低血小板黏附,这限制了它们的临床应用。因此,人血清白蛋白(HSA)的聚合提出了一种增加HSA分子大小的简单策略。
本研究旨在检验以下假设:在贫血条件下用作PE时,聚合HSA(PolyHSA)的生物物理特性可改善全身和微血管血流动力学。该研究使用仓鼠窗室模型实施。首先使用6% 70 kDa右旋糖酐将动物血液稀释至血细胞比容(Hct)为18%,然后使用10% PolyHSA、10%未聚合的HSA或6% 70 kDa右旋糖酐将其进一步稀释至Hct为11%。测量全身和微血管血流动力学,包括心输出量(CO)、平均动脉血压(MAP)、功能性毛细血管密度(FCD)、微血管灌注和氧张力。
血液稀释后,与HSA和右旋糖酐相比,PolyHSA改善了MAP、CO和氧输送。此外,PolyHSA在血流和FCD方面改善了微血管功能。尽管在Hct为11%时氧携带能力有限,但与HSA和右旋糖酐相比,PolyHSA的组织pO2和氧输送更高。
在极度贫血期间,PolyHSA通过增加血浆粘度而不增加血管阻力来支持全身和微血管血流动力学。这些发现有助于设计研究,以了解PE生物物理特性在临床场景中的作用。