NONLINEAR MODELING OF MYOCARDIAL HIGH ENERGY PHOSPHATE SYSTEM

心肌高能磷酸盐系统的非线性建模

• 批准号: 6119771
• 负责人: HONG QIAN
• 金额: $ 0.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-16 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6119771
• 关键词: Mammalia; bioengineering /biomedical engineering; biomedical resource; cardiovascular system; human tissue; technology /technique

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.

控制ATP合成和水解速率的过程 在冠状动脉灌注不足时至关重要，因为 心肌能量代谢在死亡中起主要作用， 心肌组织的存活。 心肌分析 磷能学是由热力学观点占主导地位的封闭 系统，因为高能量磷酸盐化合物具有低膜 磁导率 然而，关于心肌缺血时间进程的数据 磷酸肌酸（PCr）和ATP（NMR光谱） 灌注不足只能用开放的磷能 系统，其中缺血期间ATP分解导致产生 腺苷，这是膜渗透性和流出，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 冠状动脉血流从基线减少了95%， ATP合成和水解的速率与 控制条件 为了证实这一发现， 在缺血期间调节能量代谢的代谢途径，我们 提出了一个更完整的非线性开放系统模型， 心肌高能磷酸盐系统与代谢途径 产生膜可渗透的腺苷。 首先，ODE求解器将 用于描述细胞内代谢，间隙区域， 均匀的血管空间。 接下来，细胞模型将被嵌入到 轴向分布对流扩散血液组织交换 （BTEX）架构，以包括氧的血管运输和 核苷 最后，将模型进行了扩展， 腺苷途径的描述，包括 毛细血管内皮细胞 精确的模型和 高分辨率动力学数据将提供关于 缺血时心肌能量代谢的调节。