Diffusion Modeling and Device Development for Peritoneal Membrane Oxygenation

Diffusion Modeling and Device Development for Peritoneal Membrane Oxygenation
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腹膜氧合的扩散建模和设备开发

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发表时间:
2016
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通讯作者:
Liana Hatoum
Liana Hatoum
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作者:
Liana Hatoum

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急性呼吸窘迫综合征(ARDS)是一种引起低氧血症和呼吸衰竭的肺部疾病。ARDS的死亡率在27%到45%之间。目前的治疗包括机械通气和体外膜肺氧合(ECMO)通常与高风险并发症相关,包括气压伤、感染、血栓形成和出血。需要替代的肺支持技术来提高ARDS患者的生存率。先前的研究将纯O2气体、全氟化碳和红细胞引入腹膜内(IP)腔中,报告没有影响或仅轻度增加氧合。在这里,我们报告腹膜氧合(PMO)使用磷脂涂层氧气微泡(OMBs)。OMB是具有独特物理和化学性质的氧载体。我们假设IP输注OMB可以为患有ARDS和低氧血症的大鼠提供补充氧合,从而为肺的基本恢复提供时间。我们设计了一种推注输送装置,自动和定期输注OMB到大鼠的IP腔。此外,该装置用盐水冲洗腔体,清除灌注液,保持安全的腹腔内压力,并将灌注液温度调节至体温。为了了解腹膜内OMB输注改善全身氧合的机制,我们在理论和体内两方面研究了从OMB到健康大鼠毛细血管的氧转运动力学。一个一维的数学模型,使用菲克定律预测氧气扩散率通过腹膜。在大鼠IP腔中停留20分钟后OMB气体含量的体内测量进一步用于确定氧扩散速率,发现其在预测范围内。此外,我们能够在体内证明OMB不仅可以为身体提供O2,还可以从身体吸收CO2和其他气体,如N2。PMO代表了一种替代肺外氧合和通气技术,是未来急性呼吸衰竭的潜在治疗方法。特别感谢我的顾问和委员会主席Benjamin Terry博士,感谢他给我机会成为他实验室的研究助理,感谢他在研究过程中的指导、领导和及时的建议。我在他的实验室里学习并获得了宝贵的经验。我要感谢我的论文委员会的其他成员,基利·布辛博士和安吉拉·帕尼尔博士,他们非常慷慨地......
Acute respiratory distress syndrome (ARDS) is a pulmonary disease that causes hypoxemia and respiratory failure. The mortality rate for ARDS ranges between 27% and 45%. Current treatments including mechanical ventilation and extracorporeal membrane oxygenation (ECMO) are often associated with high risk complications including barotrauma, infection, thrombosis, and hemorrhage. Alternative pulmonary support techniques are needed to improve the survival rate of patients suffering from ARDS. Previous studies introducing pure O2 gas, perfluorocarbons and red blood cells into the intraperitoneal (IP) cavity have reported no effect or only a mild increase in oxygenation. Here we report peritoneal membrane oxygenation (PMO) using phospholipid-coated oxygen microbubbles (OMBs). OMBs are oxygen carriers that have unique physical and chemical properties. We hypothesize that IP infusion of OMBs can provide supplementary oxygenation for rats with ARDS and hypoxemia, thus allowing time for essential recovery of the lungs. We designed a bolus delivery device that automatically and periodically infuses OMBs to the rat's IP cavity. In addition, the device flushes the cavity with saline, scavenges the perfusate, maintains safe intra-abdominal pressure, and regulates perfusate temperatures to body temperature. In order to understand the mechanism by which intraperitoneal OMB infusion improves systemic oxygenation, we examined, both in theory and in vivo, the kinetics of oxygen transport from OMBs to blood capillaries of healthy rats. A 1D mathematical model was developed using Fick's laws to predict the oxygen diffusion rate across the peritoneum. In vivo measurements of the gas content of OMBs after 20 minutes of dwell time in the IP cavity of rats were further used to determine the oxygen diffusion rate, which was found to be within the predicted range. Also, we are able to demonstrate in vivo that OMBs not only can provide O2 to the body, but also can absorb CO2 and possibly other gases, such as N2, from the body. PMO represents an alternative extrapulmonary technique of oxygenation and ventilation that is a potential treatment for acute respiratory failure in the future. iv Acknowledgements A special thanks to my adviser and committee chairman Dr. Benjamin Terry for giving me the opportunity to become a research assistant in his lab and for his guidance, leadership, and timely advice over the course of the study. I learned and gained valuable experience in his lab. I wish to thank the rest of my thesis committee, Dr. Keely Buesing and Dr. Angela Pannier, who were more than generous with …
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