超快速反应聚合物光纤氧测定装置及其用于活体动物机械通气下动脉血氧分压连续动态变化的初步实验报告*

doi:10.12047/j.cjap.0088.2021.112

中国应用生理学杂志 ›› 2021, Vol. 37 ›› Issue (1): 104-112.doi: 10.12047/j.cjap.0088.2021.112

• 研究论文 • 上一篇

超快速反应聚合物光纤氧测定装置及其用于活体动物机械通气下动脉血氧分压连续动态变化的初步实验报告^*

孙兴国¹, 陈荣声², 王桂芝³, 杨希营³, 赵晓勇³, 于剑锋³, 张蕊³, 冀玉萍^3,4, 李军^3,4, 李浩¹, 张也¹, 马铭欣^1,5, 陈荣^1,5, 邹昱馨^1,6

1.国家心血管病中心中国医学科学院阜外医院心血管疾病国家重点实验室国家心血管疾病临床医学研究中心,北京协和医学院,北京 100037,中国;
2.牛津大学,牛津OX 1 2JD,英国;
3.潍坊医学院,山东潍坊 261053,中国;
4.潍坊市中医院,山东潍坊 261041,中国;
5.辽宁省大连儿童医院,大连 116000,中国;
6.山东省聊城市立医院儿童医院,聊城 252000,中国

收稿日期:2020-08-12 修回日期:2021-01-12 发布日期:2021-10-21
通讯作者: ^△Tel：010-88398300;E-mail: xgsun@lundquist.org
基金资助:
^*国家高技术研究发展计划（863计划）课题资助项目（2012AA021009）; 国家自然科学基金医学科学部面上项目（81470204）; 中国康复医疗机构联合重大项目基金（20160102）; 中国医学科学院国家心血管病中心阜外医院科研开发启动基金（2012-YJR02）; 首都临床特色应用研究与成果推广（Z161100000516127）; 北京康复医院2019-2021科技发展专项（2019-003）; 北京协和医学院教学改革项目（2018E-JG07）; 北京协和医学院-国家外国专家局外国专家项目（2015,2016,T2017025,T2018046,G2019001660）; 重庆市卫计委医学科研计划项目（2017MSXM090）; 重庆市科委社会事业与民生保障科技创新专项项目（cstc2017shmsA130063）

Ultra-fast response polymer optical fiber oxygen measurement device and its preliminary experimental report on continuous dynamic change of arterial oxygen partial pressure under mechanical ventilation in living animals

SUN Xing-guo¹, CHEN Rong-sheng², WANG Gui-zhi³, YANG Xi-ying³, ZHAO Xiao-yong³, YU Jian-feng³, ZHANG Rui³, JI Yu-ping^3,4, LI Jun^3,4, LI Hao¹, ZHANG Ye¹, MA Ming-xin^1,5, CHEN Rong^1,5, ZOU Yu-xin^1,6

1. Fuwai Hospital,Chinese Academy of Medical Sciences/National Center for Cardiovascular Diseases/ State Key Laboratory of Cardiovascular Diseases/Chinese Academy of Medical Sciences/Peking Union Medical College,Beijing 100037,China;
2. Oxford University, Oxford OX1 2JD, UK;
3. Weifang Medical University, Weifang 261053, China;
4. Weifang Hospital of Traditional Chinese Medicine, Weifang 261041, China;
5. T. Dalian Children's Hospital,Dalian 116000,China;
6. Liaocheng People's Hospital,Liaocheng 252000,China

Received:2020-08-12 Revised:2021-01-12 Published:2021-10-21

摘要/Abstract

摘要： 目的: 我们在中国尝试使用超快反应聚合物光纤氧感受器置入整体活体动物动脉血管,再通过光电转换测定系统以记录活体动物颈动脉PO₂（PaO₂）连续动态的快速变化,为完善整体整合生理学理论体系中循环参与呼吸调控和呼吸循环代谢一体化调控提供实验依据。方法: ①超快反应氧感受器制作、性能及其测定系统标定：在实验室加热总长2 m光纤的远端5 mm部分,拉动直到它成锥形尖端,清洁并干燥后,将1 mm锥形光纤尖端浸涂到发光体掺杂聚合物溶液中,在溶剂快速蒸发同时将其缓慢抽出来形成氧气感测尖端,室温干燥24 h。对完成制作的感受器进行性能标定,并于第37日重复标定。②动物实验：在潍坊医学院实验室对山羊全麻气管插管氧气机械通气下,切皮暴露双颈动脉和左侧股动脉,分别把超快反应氧传感器直接插入动脉中,通过光导纤维、激发与检测Y型光纤耦合器经光电转换连接到个人电脑,实现机械通气下活体山羊颈动脉PaO₂的连续动态反应,主要分析PaO₂的呼吸间波浪式交替升降和肺-颈动脉时间延迟。结果: 该置入式超快反应氧传感器在液相的响应时间为100 ms。活体山羊实验40%~60%氧气机械通气心率和血压稳定,左和右颈动脉PaO₂随着呼吸机的吸气和呼气呈现波浪式上升和下降的呼吸交替现象,幅度高达15 mmHg;左侧股动脉位置记录的信息噪音显著干扰PaO₂变化。肺-颈动脉时间延迟是在吸气和呼气开始后1.5~1.7 s左侧和右侧颈动脉PaO₂都开始上升和下降;即肺通气开始后3次心跳,左心室可把肺毛细血管后动脉化的肺静脉血液送到外周化学感受器位置中断吸气切换为呼气和中断呼气切换为吸气,如此实现吸呼周而复始。结论: 活体动物置入动脉的超快反应氧传感器及其测定系统可测定PaO₂生理性波浪式变化,能为整体整合生理学医学新理论体系中解释吸气和呼气相互切换的机制提供实验依据。

关键词: 超快反应聚合物光纤氧传感器, 整体整合生理学医学, 活体整体动物, 动脉血氧分压波动幅度, 肺-动脉时间延迟, 呼吸调节控制信号, 吸气和呼气相互切换机制

Abstract: Objective: We tried to implant the ultra-fast polymer optical fiber chemical oxygen sensor （POFCOS） into arterial blood vessel,connect with photoelectric conversion measurement system to record the continuous dynamic rapid changes of arterial PO₂(PaO₂) in whole living animals. It should be the experimental evidence for the new theory of holistic integrative physiology and medicine(HIPM) forexplain the mechanism of respiratory control and regulation in whole circusof respiration-circulation-metabolism. Methods: ①Fabrication of ultrafast POFCOS, calibration and its measuring system: The distal part of 2 m optical fiber was heated and pulled until it became a tapered tip. After cleaning and drying, the tip of 1 mm tapered optical fiber was dip-coated into the luminophore doped polymer solution, then was slowly pumped out while solvent was quickly evaporated to form an oxygen sensing tip, which was dried at room temperature for 24 hours. ②Animal experiments: Under general anesthesia and intubation, goatwas mechanically ventilated with 40%~60% oxygen. We exposed both right and left carotid arteries and the left femoral artery by skin cutting, and inserted the POFCOS directly into the arteries via indwelling catheter. The end of POFCOS were connected to the personal computer through optical fiber, excitation and detection Y-type optical fiber coupler through photoelectric conversion, so as we can realize the continuous dynamic response of living goat carotid PaO₂ under mechanical ventilation. We mainly analyzed the intra-breath wave-form alternate increase and decrease of PaO₂ and their time delay between lung and carotid arteries.We completes breathing control whole loop to explain the mechanism of mutual breathing and the switching of inspiration and exhalation. Results: The POFCOS has a very fast T90 response time was set 100 ms for liquid. When the heart rate of 40%~60% oxygen mechanical ventilated living goat was ~110 bpm, the PaO₂ of left and right carotid artery showed a same wave-sizeup and down following with the inspiration and expiration of ventilator, with a range of up to 15 mmHg. There weresignificant noises of PaO₂change recorded in the left femoral artery. The lung-carotid artery time delay is 1.5~1.7 s after inhalation and exhalation, PaO₂ at both left and right carotid arteries starts toincrease and decrease. After two-three heartbeats after the start of lung ventilation, thealternate up-down wave-form information of the arterialized pulmonary vein blood after pulmonary capillaries waspumpedby left ventricle to the position of peripheral chemoreceptors,thus realizing the whole cycle of inhalation and exhalation. It alternately interrupted inhalation, i.e. switching inhalation to exhalation, and then interrupted exhalation,i.e. switching exhalation to inhalation. Conclusion: The ultra-fast reactive implantableoxygen sensor and its measuring system can measure the physiological waveform changes of PaO₂in living animals, which can provide experimental evidence for explaining the mechanism of switching of inspiration-expiration in HIPM.

Key words: ultra-fast reaction polymer optical fiber oxygen sensor, holistic integrative physiology and medicine, living whole animal, fluctuation of arterial oxygen partial pressure, lung-artery time delay, respiratory regulation control signal, mechanism of inspiration-expiration switching

中图分类号:

R332

孙兴国, 陈荣声, 王桂芝, 杨希营, 赵晓勇, 于剑锋, 张蕊, 冀玉萍, 李军, 李浩, 张也, 马铭欣, 陈荣, 邹昱馨. 超快速反应聚合物光纤氧测定装置及其用于活体动物机械通气下动脉血氧分压连续动态变化的初步实验报告^*[J]. 中国应用生理学杂志, 2021, 37(1): 104-112.

SUN Xing-guo, CHEN Rong-sheng, WANG Gui-zhi, YANG Xi-ying, ZHAO Xiao-yong, YU Jian-feng, ZHANG Rui, JI Yu-ping, LI Jun, LI Hao, ZHANG Ye, MA Ming-xin, CHEN Rong, ZOU Yu-xin. Ultra-fast response polymer optical fiber oxygen measurement device and its preliminary experimental report on continuous dynamic change of arterial oxygen partial pressure under mechanical ventilation in living animals[J]. CJAP, 2021, 37(1): 104-112.

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超快速反应聚合物光纤氧测定装置及其用于活体动物机械通气下动脉血氧分压连续动态变化的初步实验报告^*

Ultra-fast response polymer optical fiber oxygen measurement device and its preliminary experimental report on continuous dynamic change of arterial oxygen partial pressure under mechanical ventilation in living animals

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