Integrated cardiopulmonary modelling for the investigation of the management of disturbed tissue perfusion

对低心输出量状态(血液流入器官不足，导致器官损伤)的管理研究很少。这些“休克”状态是危重疾病的常见特征，并消耗了医疗保健预算的很大一部分。由于人类和动物模型的复杂性，以及测量感兴趣的结果的难度，以前研究休克状态的尝试得到了相互矛盾的结果。利用多器官的计算机模拟可以对这个问题进行更详细和深入的研究，这是我们提出的项目的基础。这项研究的结果将直接适用于危重患者，并有可能挽救许多人的生命，减少医疗支出。第一步：我们将设计和开发开创性的心脏、血管和组织的计算机模拟。我们将把这些与我们现有的、已发表的肺部模拟结合起来。由此产生的多器官模拟将包括这些器官系统的结构和功能的详细信息，并将允许对微观区域进行非常详细的询问，以确定危重患者器官系统和治疗策略之间的相互作用。第二步：我们将应用突破性的验证(测试)技术来测试和改进新的多器官模型的准确性和实用性；这些将包括来自空间和飞行控制工程的技术，以及我们实验室针对个体患者监测数据和以前的临床研究设计的“智能”验证技术。第三步：使用多器官模型，我们将研究休克状态的受扰生理学和潜在的治疗策略。首先，我们将解决对正常功能障碍知之甚少的方面，以及影响组织血流和氧合的可能性(例如，肺保护性生命支持如何影响休克期间的器官氧合？)。第四步：利用前一阶段产生的知识，我们将构建管理各种类型休克状态的简单算法，并在大量模拟受试者中测试这些算法，评估算法改善休克结果的能力。结果：该项目的成功完成将产生新的多器官模型，这些模型可重复用于研究危重疾病，更好地了解休克状态和潜在的治疗途径，最后，可用于患者护理的治疗，以优化治疗具有休克状态的危重患者的方法。

The management of low cardiac output states (where inadequate blood flows to the organs, causing organ damage) is poorly researched. These "shock" states are a common feature of critical illness, and consume a large part of the healthcare budget. Previous attempts to investigate shock states have had conflicting results because of the complexity of human and animal models, and the difficulty of measuring outcomes of interest. This issue could be investigated in great detail and depth using computer simulation of multiple organs, and this is the basis of our proposed project. Findings from this research will be directly applicable to critically ill patients, and have the potential to save many lives and reduce healthcare expenditure.Step 1: We will design and develop ground-breaking computer simulations of heart, blood vessels and tissue. We will combine these with our existing, published lung simulation. The resulting, multiple organ simulation will include great detail of the structure and function of these organ systems and will allow very detailed interrogation of microscopic areas to determine the interaction between organ systems and treatment strategies in critically ill patients.Step 2: We will apply ground-breaking validation (testing) techniques to test and improve the accuracy and usefulness of the new multi-organ models; these will include techniques from space and flight-control engineering and techniques designed in our labs for "smart" validation against individual patient monitoring data and previous clinical studies.Step 3: Using the multi-organ models we will investigate the disturbed physiology of shock states and potential treatment strategies. Initially, we will address poorly understood aspects of the disorder of normal function, and the potential to affect tissue blood flow and oxygenation (e.g. how does lung-protective life-support affect organ oxygenation during shock?). Step 4: Using the knowledge generated in the previous phase, we will construct simple algorithms for the management of various types of shock state and test these in a large population of simulated subjects, assessing the ability of the algorithms to improve outcome from shock.Outcomes: Successful completion of the project will yield novel multi-organ models that may be re-used in investigating critical illness, greater understanding of shock states and potential treatment pathways, and, finally, treatments that may be used in patient care to optimise methods of treating critically ill patients with shock states.