NONLINEAR MODELING OF MYOCARDIAL HIGH ENERGY PHOSPHATE SYSTEM

控制三磷酸腺苷合成和水解率的过程 在冠状动脉灌注不足期间是至关重要的，因为 心肌能量代谢在死亡或死亡中起主要作用 心肌组织的存活率。心肌病的分析 光能是由一个封闭的热力学观点支配的 系统，因为高能磷酸盐化合物具有低膜 渗透性。然而，关于心肌梗死时间进程的数据 冠状动脉病变过程中的磷酸肌酸和三磷酸腺苷核磁共振波谱 血流灌注不足只能用开放的磷光能来描述 系统，在此系统中，ATP在缺血时的分解导致产生 腺苷，它是膜通透性的，从 系统。通过使用一种新的开放系统动力学 初步模型，我们得到了令人惊讶的结果，即使当 冠脉流量比基线减少了95%， 三磷酸腺苷合成和水解率与 控制条件。承认这一发现并探索 在缺血期间调节能量代谢的代谢途径，我们 提出了一种更完整的非线性开放系统模型，并将 心肌高能磷酸盐系统及其代谢途径 产生膜透性腺苷。首先，一个颂歌解算器将是 用来描述细胞内代谢，间质区域，和 一个统一的血管空间。接下来，细胞模型将嵌入到 轴向分布的对流扩散式血液组织交换 (BTEX)架构，包括氧气的血管传输和 核苷。最后，对模型进行了扩展，使之更加完善 腺苷途径的描述，包括腺苷的摄取 毛细血管内皮细胞。准确的模型和 高分辨率动力学数据将提供全新的视角 缺血时心肌能量代谢的调节。

The processes governing the rates of ATP synthesis and hydrolysis are of critical importance during coronary underperfusion, since myocardial energy metabolism plays a primary role in the death or survival of myocardial tissue. Analysis of myocardial phosphoenergetics is dominated by the thermodynamic view of a closed system, since high energy phosphate compounds have low membrane permeability. However, data on the timecourse of myocardial phosphocreatine (PCr) and ATP (NMR spectroscopy) during coronary underperfusion can only be described by an open phosphoenergetic system, in which ATP breakdown during ischemia causes the production of adenosine, which is membrane permeable and effluxes from the system. By accounting for novel open system kinetics using a preliminary model, we obtained the surprising result that even when coronary flow was reduced by 95% from baseline, the matching of the rates of ATP synthesis and hydrolysis was just as precise as under control conditions. To confir m this finding and explore the metabolic pathways that regulate energy metabolism during ischemia, we propose a more complete nonlinear open system model, linking the myocardial high energy phosphate system with the metabolic pathways producing membrane permeable adenosine. First, an ODE solver will be used to describe intracellular metabolism, an interstitial region, and a uniform vascular space. Next, the cell model will be embedded in the axially distributed convection-diffusion blood-tissue exchange (BTEX) architecture, to include vascular transport of oxygen and nucleosides. Finally, the model will be extended for a more complete description of adenosine pathways, including adenosine uptake in capillary endothelial cells. The combination of an accurate model and high resolution kinetic data will provide completely new insight on the regulation of myocardial energy metabolism during ischemia.