Department of Anesthesiology and Critical Care, Medical Center, University of Freiburg, Faculty of Medicine, Germany.
Institute for Pharmacy and Food Chemistry, University of Würzburg, Germany.
J Control Release. 2018 Jun 10;279:336-344. doi: 10.1016/j.jconrel.2018.04.017. Epub 2018 Apr 12.
Carbon monoxide (CO) has demonstrated therapeutic potential in multiple inflammatory conditions including intensive care applications such as organ transplantation or sepsis. Approaches to translate these findings into future therapies, however, have been challenged by multiple hurdles including handling and toxicity issues associated with systemic CO delivery. Here, we describe a membrane-controlled Extracorporeal Carbon Monoxide Release System (ECCORS) for easy implementation into Extracorporeal Membrane Oxygenation (ECMO) setups, which are being used to treat cardiac and respiratory diseases in various intensive care applications. Functionalities of the ECCORS were investigated in a pig model of veno-arterial ECMO. By precisely controlling CO generation and delivery as a function of systemic carboxyhemoglobin levels, the system allows for an immediate onset of therapeutic CO-levels while preventing CO-toxicity. Systemic carboxyhemoglobin levels were profiled in real-time by monitoring exhaled CO levels as well as by pulse oximetry, enabling self-contained and automatic feedback control of CO generation within ECCORS. Machine learning based mathematical modeling was performed to increase the predictive power of this approach, laying foundation for high precision systemic CO delivery concepts of tomorrow.
一氧化碳（CO）在多种炎症性疾病中显示出治疗潜力，包括重症监护应用，如器官移植或败血症。然而，将这些发现转化为未来疗法的方法受到多种障碍的挑战，包括与全身 CO 输送相关的处理和毒性问题。在这里，我们描述了一种膜控体外 CO 释放系统（ECCORS），可轻松集成到体外膜氧合（ECMO）设备中，该系统用于治疗各种重症监护应用中的心脏和呼吸疾病。在静脉-动脉 ECMO 的猪模型中研究了 ECCORS 的功能。通过精确控制 CO 的产生和输送作为全身碳氧血红蛋白水平的函数，该系统允许立即达到治疗性 CO 水平，同时防止 CO 毒性。通过监测呼出的 CO 水平和脉搏血氧饱和度，实时分析系统碳氧血红蛋白水平，从而实现 ECCORS 内 CO 产生的自我包含和自动反馈控制。基于机器学习的数学建模用于提高该方法的预测能力，为未来高精度全身 CO 输送概念奠定基础。
