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Mathematical Model of NO and O2 Transport in an Arteriole Facilitated by Hemoglobin Based O2 Carriers

机译：血红蛋白基O2载体促进小动脉中NO和O2传输的数学模型

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The increasing demand for donated human blood has spurred research to develop hemoglobin-based O2 carriers (HBOCs) that can be used as red blood cell (RBC) substitutes. However, in vivo studies of acellular HBOCs have shown an increase in mean arterial pressure following transfusion that has been attributed to the HBOC’s ability to scavenge NO (an important vasodilator that is synthesized by endothelial cells in the blood vessel wall that signals neighboring smooth muscle cells to relax). In this study, a mathematical model was developed to describe NO and O2 transport in an arteriole containing a mixture of acellular HBOCs and RBCs. The acellular HBOCs studied in this work possessed a wide range of O2 affinities, O2 dissociation rate constants and NO reactivities in order to evaluate their effect on O2 tension and NO concentration in the arteriole tissue region. By focusing on the concentration of NO that is localized in the arteriole smooth muscle cell region, the model can predict the vasopressor response of HBOCs. The results of this study confirmed that acellular HBOCs scavenge large amounts of NO from the entire arteriole (∼ 50% or more NO compared to RBCs only). A recombinant Hb, rHb3011, displayed the least NO reactivity and consequently left the most NO remaining in the arteriole. The NO concentration in the arteriole with respect to the other HBOCs studied was proportional to their NO reactivity. Therefore, the results of this study demonstrate that NO scavenging is an unavoidable consequence of transfusing HBOCs. To prevent or reduce vasodilatation, we suggest administration of NO by either inhaling NO or transfusing nitrite into the blood stream followed by transfusion of HBOC.
机译：对捐赠人血的需求不断增加，促使人们研究开发基于血红蛋白的O2载体（HBOC），可以将其用作红细胞（RBC）的替代品。但是，对脱细胞HBOC的体内研究表明，输血后平均动脉压升高，这归因于HBOC清除NO（血管壁内皮细胞合成的重要血管扩张剂，该信号向邻近的平滑肌细胞发出信号）放松）。在这项研究中，开发了一个数学模型来描述在包含无细胞HBOC和RBC混合物的小动脉中NO和O2的运输。在这项工作中研究的脱细胞HBOC具有广泛的O2亲和力，O2解离速率常数和NO反应性，以评估它们对小动脉组织区域中O2张力和NO浓度的影响。通过关注位于小动脉平滑肌细胞区域中的NO浓度，该模型可以预测HBOC的血管升压反应。这项研究的结果证实，脱细胞的HBOC从整个小动脉中清除了大量的NO（与仅RBC相比，NO约为5​​0％或更多）。重组Hb rHb3011显示最低的NO反应性，因此留在小动脉中的NO最多。相对于所研究的其他HBOC，小动脉中的NO浓度与其NO反应性成正比。因此，这项研究的结果表明，清除NO是清除HBOC的不可避免结果。为了预防或减少血管舒张，我们建议通过吸入NO或将亚硝酸盐输入血流，然后输注HBOC来给予NO。

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