Abstract：
The widespread adoption of high-calorie, high-fat, high-sucrose diets (HFHSD) has become a global health concern, particularly due to their association with cardiovascular diseases and metabolic disorders. These comorbidities increase susceptibility to severe outcomes from viral infections and trauma, with trauma-related incidents significantly contributing to global mortality rates. This context underscores the critical need for a reliable blood supply. Recent research has focused on high molecular weight (MW) polymerized human hemoglobin (PolyhHb) as a promising alternative to red blood cells (RBCs), showing encouraging outcomes in previous studies. Given the overlap of metabolic disorders and trauma-related health issues, it is crucial to assess the potential toxicity of PolyhHb transfusions, particularly in models that represent these vulnerable populations. This study evaluated the effects of PolyhHb exchange transfusion in guinea pigs that had developed metabolic disorders due to a 12-week HFHSD regimen. The guinea pigs, underwent a 20 % blood volume exchange transfusion with either PolyhHb or the lower molecular weight polymerized bovine hemoglobin, Oxyglobin. Results revealed that both PolyhHb and Oxyglobin transfusions led to liver damage, with a more pronounced effect observed in HFHSD-fed animals. Additionally, markers of cardiac dysfunction indicated signs of cardiac injury in both the HFHSD and normal diet groups following the Oxyglobin transfusion. This study highlights how pre-existing metabolic disorders can exacerbate the potential side effects of hemoglobin-based oxygen carriers (HBOCs). Importantly, the newer generation of high MW PolyhHb showed lower cardiac toxicity compared to the earlier generation low MW PolyhHb, known as Oxyglobin, even in models with pre-existing endothelial and metabolic challenges.
摘要：
高热量的广泛采用，高脂肪,高蔗糖饮食（HFHSD）已成为全球健康问题，特别是由于它们与心血管疾病和代谢紊乱有关。这些合并症增加了对病毒感染和创伤的严重后果的易感性，与创伤相关的事件对全球死亡率有显著影响。这种情况强调了对可靠血液供应的迫切需要。最近的研究集中在高分子量（MW）聚合的人血红蛋白（PolyhHb）作为红细胞（RBC）的有希望的替代品，在以前的研究中显示出令人鼓舞的结果。鉴于代谢紊乱和创伤相关健康问题的重叠，评估PolyhHb输血的潜在毒性至关重要，特别是在代表这些弱势群体的模型中。这项研究评估了PolyhHb交换输血对由于12周HFHSD方案而发生代谢紊乱的豚鼠的影响。豚鼠,用PolyhHb或较低分子量的聚合牛血红蛋白进行20％的血液体积交换输血，氧球蛋白.结果显示，无论是PolyhHb和氧球蛋白输血导致肝损伤，在饲喂HFHSD的动物中观察到更明显的效果。此外,心功能障碍的标志物表明在输注氧球蛋白后,HFHSD和正常饮食组均有心脏损伤的迹象.这项研究强调了预先存在的代谢紊乱如何加剧基于血红蛋白的氧载体（HBOC）的潜在副作用。重要的是,与上一代低MWPolyhHb相比，新一代高MWPolyhHb显示出更低的心脏毒性，被称为氧球蛋白，即使在预先存在内皮和代谢挑战的模型中。
