Mathematical Modeling Study Of Vascular Regulation In Microcirculatory Network

Cardiovascular diseases(CVDs)are global leading cause of death.The prevention,diagnosis and treatment of CVDs are great challenges.The study of cardiovascular physiological and pathological properties plays an essential role in the research of CVDs.Microcirculation is an important component of cardiovascular systems,and its functional characteristics is one of the key issues in research of cardiovascular physiology and pathology.The main function of microcirculation is to supply adequate oxygen and other metabolites to meet the needs of tissues and organs.Furthermore,the microcirculation must possess the ability of vascular regulation to adapt structurally to the changes in functional needs.The vascular regulation in microcirculation is extremely complex,but fortunately the mathematical models provide a quantitative and effective way for studying the mechanisms of vascular regulation in microcirculation.At present,most of the models were based on ideal network of micro-vessels,neglecting the heterogeneity of vascular structure,blood flow distribution and the functions in the realistic vascular networks,which limits the application of the models.The models based on realistic vascular networks can reflect the heterogeneous flow distribution and network functions,which improves the authenticity of the model simulation and benefits the practical application of vascular regulation models in relevant physiological and clinical studies.However,the models based on realistic vascular networks have defects in regulation mechanism modeling,parameter optimization and model stability,in particular,the coupled modeling of short-term and long-term vascular regulation mechanism.This dissertation aims to study the key modeling technologies of regulation mechanism modeling,parameter optimization and model stability,and then develop the models of short-term regulation,long-term regulation and their interaction based on the realistic data of experimental microcirculatory network.Accordingly,these mechanisms of vascular regulation and their impact on the occurrence and development of CVDs were investigated.The main contributions of this study are summarized as follows:1.A structural adaptation model focusing on the long-term regulation of vessels was constructed.Numerical computing techniques were applied to improve the computational stability on hemodynamics and the efficiency of adaptive parameters optimization.Based on this model,the synergistic effect of multiple adaptive signals and the abnormal functions of network in the absence of adaptive signals were investigated.The result indicates the importance of synergistic effect of multiple adaptive signals on long-term vascular regulation in microcirculation.2.A pulsatile flow-mediated vascular tone regulation model was proposed based on the mechanism of pulsatile flow-endothelial nitric oxide(NO)-diameter regulation.With the help of the model,it is discovered that frequency and amplitude of inlet pulsatile flow have different effects on the damping of blood flow pulsatility and the consequent vascular regulation.3.The structural adaptation model and vascular tone regulation model were coupled.By the coupled model the interaction between short-term and long-term regulation in vascular network was investigated.4.The application of above models in the simulation of pathological conditions was assessed,and the interaction between vascular regulation and network structure/function was analyzed under hypertension and ischemia condition.The simulation explored that abnormal vascular regulation will lead to hypertension and aggravate ischemia in microcirculation.This result is consistent with the clinical findings,verifying the validation of these models in pathological simulation.The main innovations of the dissertation are:1.An improved quantum particle swarm optimization(QPSO)algorithm was proposed,which effectively solved the problem of parameter optimization in vascular regulation model of microcirculation,and thus enhanced the applicability of the model.2.A pulsatile flow related vascular tone regulation model was proposed.This model enables the simulation of pulsatile flow and its regulation mechanism in vascular network,which provides a novel method for studying the pulsatility in microcirculation.3.A coupled model of short-term and long-term regulation was proposed based on the parameter of nitric oxide.The model fills the gap of methodology in studying the interaction between short-term and long-term regulation in complex vascular network.Moreover,it provides a useful technical exploration and model framework for promoting the multi-scale and multi-mechanism coupling research in the vascular regulation modeling of microcirculation.In conclusion,the proposed vascular regulation models involving the short-term and long-term changes of vascular network structure provide an effective tool for quantitative study of vascular regulation mechanisms in microcirculation.With further improvement,the models are potential to benefit the fundamental CVDs research and facilitate the prevention and treatment of CVDs.