A physiological model of the inflammatory‐thermal‐pain‐cardiovascular interactions during an endotoxin challenge
A physiological model of the inflammatory‐thermal‐pain‐cardiovascular interactions during an endotoxin challenge
复制标题
内毒素挑战期间炎症-热-疼痛-心血管相互作用的生理模型
DOI：
10.1113/jp280883
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Olufsen, Mette S.
中科院分区：
文献类型：
--
作者：
Dobreva, Atanaska;Brady‐Nicholls, Renee;Larripa, Kamila;Puelz, Charles;Mehlsen, Jesper;Olufsen, Mette S.
细菌内毒素引起的炎症反应会影响生理功能，包括心血管、热动力学和疼痛动力学，尽管机制尚不清楚。我们开发了一个创新的数学模型，结合了内毒素挑战反应中炎症和生理过程之间的相互作用途径。我们将模型校准为来自20名受试者的人体炎症和内毒素生理反应实验研究中的个人数据，并根据来自独立研究的人体数据验证模型。使用该模型来模拟患者对不同治疗方式的反应，揭示了多模式治疗结合几种治疗策略可以获得最佳的恢复结果。来自免疫细胞和创伤组织的促炎介质不受控制的过量产生可引起全身性炎症，如败血症，败血症是美国十大死亡原因之一，也是重症监护病房的三大死亡原因之一。了解炎症如何影响生理过程，包括心血管、热和疼痛动力学，可以提高患者在手术或严重感染引起的炎症事件后恢复的机会。尽管自主神经反应对炎症系统的影响是众所周知的，但对其反向相互作用的了解还很缺乏。本研究建立了一个数学模型，分析炎症系统在应对细菌内毒素挑战时与热、疼痛和心血管动力学的相互作用。我们使用来自20名健康年轻男性一次性内毒素治疗的炎症和生理反应实验研究的个人数据校准模型，并根据独立内毒素研究的数据验证模型。我们使用模拟来探索各种治疗方法如何帮助暴露于持续病理输入的患者。探索的治疗方法包括细菌内毒素吸附、解热药和血管加压药，以及这些药物的组合。我们的研究结果表明，最有利的恢复结果是通过多模式策略实现的，将所有三种干预措施结合起来，同时从体内清除内毒素并减轻免疫系统在对抗感染时引起的症状。
Key pointsInflammation in response to bacterial endotoxin challenge impacts physiological functions, including cardiovascular, thermal and pain dynamics, although the mechanisms are poorly understood.We develop an innovative mathematical model incorporating interaction pathways between inflammation and physiological processes observed in response to an endotoxin challenge.We calibrate the model to individual data from 20 subjects in an experimental study of the human inflammatory and physiological responses to endotoxin, and we validate the model against human data from an independent study.Using the model to simulate patient responses to different treatment modalities reveals that a multimodal treatment combining several therapeutic strategies gives the best recovery outcome.AbstractUncontrolled, excessive production of pro‐inflammatory mediators from immune cells and traumatized tissues can cause systemic inflammatory conditions such as sepsis, one of the ten leading causes of death in the USA, and one of the three leading causes of death in the intensive care unit. Understanding how inflammation affects physiological processes, including cardiovascular, thermal and pain dynamics, can improve a patient's chance of recovery after an inflammatory event caused by surgery or a severe infection. Although the effects of the autonomic response on the inflammatory system are well‐known, knowledge about the reverse interaction is lacking. The present study develops a mathematical model analyzing the inflammatory system's interactions with thermal, pain and cardiovascular dynamics in response to a bacterial endotoxin challenge. We calibrate the model with individual data from an experimental study of the inflammatory and physiological responses to a one‐time administration of endotoxin in 20 healthy young men and validate it against data from an independent endotoxin study. We use simulation to explore how various treatments help patients exposed to a sustained pathological input. The treatments explored include bacterial endotoxin adsorption, antipyretics and vasopressors, as well as combinations of these. Our findings suggest that the most favourable recovery outcome is achieved by a multimodal strategy, combining all three interventions to simultaneously remove endotoxin from the body and alleviate symptoms caused by the immune system as it fights the infection.
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影响因子：
16.8
作者：
Pinho-Ribeiro FA;Verri WA Jr;Chiu IM
通讯作者：
Chiu IM
急性高热对颈动脉压力反射控制心率的影响
影响因子：
3.2
作者：
F. Yamazaki;S. Sagawa;R. Torii;Y. Endo;K. Shiraki
通讯作者：
K. Shiraki
影响因子：
3.1
作者：
S. Chesrown;J. Monnier;G. Visner;H. Nick
通讯作者：
S. Chesrown;J. Monnier;G. Visner;H. Nick
DOI：
10.1097/mss.0b013e31803349c6
发表时间：
2007-05-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Gellish, Ronald L.;Goslin, Brian R.;Moudgil, Virinder K.
通讯作者：
Moudgil, Virinder K.
影响因子：
4.6
作者：
J. D. Scheff;P. D. Mavroudis;S. Calvano;S. Lowry;I. Androulakis
通讯作者：
J. D. Scheff;P. D. Mavroudis;S. Calvano;S. Lowry;I. Androulakis