Estep Timothy N
Chart Biotech Consulting, LLC, Erie, CO, United States.
Front Physiol. 2025 Apr 15;16:1551932. doi: 10.3389/fphys.2025.1551932. eCollection 2025.
Development of hemoglobin-based oxygen carriers (HBOCs) for use as temporary blood replacement solutions and treatment of hemorrhagic shock has been hindered because of evidence HBOC infusion increases the risk of myocardial infarction (MI).
To gain insight into potential toxicity mechanisms, MI incidence from later stage clinical testing of five HBOCs was compared to pharmacokinetic and biochemical parameters to identify correlations suggestive of cause-and-effect hypotheses.
There are positive correlations between MI incidence and HBOC dose, size, intravascular half-life and area under the plasma concentration versus time curve (AUC). Furthermore, MI incidence is positively correlated with initial rates of HBOC autoxidation, oxidation by nitric oxide, and AUCs estimated for these HBOC oxidation products.
These observations imply that increased MI risk after HBOC infusion is due to intravascular reactions which exacerbate oxidative stress.
基于血红蛋白的氧载体（HBOCs）作为临时血液替代溶液和治疗失血性休克的开发一直受到阻碍，因为有证据表明输注HBOCs会增加心肌梗死（MI）的风险。
为了深入了解潜在的毒性机制，将五种HBOCs后期临床试验中的MI发生率与药代动力学和生化参数进行比较，以确定暗示因果假设的相关性。
MI发生率与HBOC剂量、大小、血管内半衰期以及血浆浓度-时间曲线下面积（AUC）之间存在正相关。此外，MI发生率与HBOC自氧化的初始速率、一氧化氮氧化以及这些HBOC氧化产物的估计AUC呈正相关。
这些观察结果表明，输注HBOCs后MI风险增加是由于血管内反应加剧了氧化应激。
