Replacement of animal models of cardiac arrest and resuscitation strategies using a computer simulation

心脏骤停可能是由各种病理和事件引起的，导致心脏停止向全身和大脑输送血液，导致意识丧失和呼吸停止。早期应用心肺复苏术(CPR)可显著改善预后。然而，胸部按压、肺部通风和复苏后护理的最佳组合尚未确定。许多人体试验试图确定最优的CPR策略；然而，伦理限制、时间尺度、混杂变量的存在、人群的异质性和样本量是主要障碍。同样，由于物种间的生理差异和缺乏方法学的严谨性，许多动物模型无法总结人类临床心脏骤停的严重程度。计算模型为研究这些难以理解的问题提供了一种新的、强大的方法。与动物模型和人类实验不同，个性化患者和疾病病理的硅胶模型可以修改为详细的验证，确保重复性和转化为人类应用。被任命的博士生Clara Daudre-Vignier正在使用并进一步开发系统医学跨学科协作(ICSM)模拟套件，这是一套集成的高保真心肺模型，由Hardman教授和他的团队开发，目的是：1.描述与人类心脏骤停相关的病理生理变化2。对心脏骤停的病理生理状态有了新的认识。开发和测试新的CPR策略4。探讨心脏骤停后的临床处理策略5。制定新的复苏内和复苏后个体化策略。

Cardiac arrest may be caused by a variety of pathologies and events, causing the heart to stop pumping blood around the body and to the brain, causing loss of consciousness and cessation of breathing. Outcome may be improved significantly by the early use of cardiopulmonary resuscitation (CPR). However, the optimal combination of chest compressions and ventilation of the lungs and post-resuscitation care have not been established. Many human trials have attempted to identify the optimal CPR strategy; however the ethical constraints, time scale, the presence of confounding variables, the heterogeneity of the population and sample size present major obstacle. Similarly, many animal models fail to summarize the severity of human clinical cardiac arrest due to interspecies physiological discrepancies and lack of methodical rigour.Computational modelling offers a novel and powerful approach to research into such inaccessible issues. In contrast to trials on animal models and humans, in-silico models of individualised patient and disease-pathology are amendable to detailed validation, assuring reproducibility and translation into human application. The PhD student appointed, Clara Daudre-Vignier, is using and further developing the Interdisciplinary Collaboration in Systems Medicine (ICSM) simulation suite, a set of integrated, high-fidelity cardiopulmonary models, developed by Prof Hardman and his team, to:1. describe the pathophysiological changes associated with cardiac arrest in-silico humans2. obtain novel understanding of the pathophysiological state of cardiac arrest3. develop and test new CPR strategies4. investigate clinical management strategies after cardiac arrest5. develop new intra- and post-resuscitation individualized strategies.