Modeling the cardiopulmonary-arterial baroreflexes

The objective of this project is to develop a physiologically based mathematical model of the cardiovascular system (CVS) that can be applied to study the short-term control of hypovolemic stress. The primary goal will be to develop a model that can quantitatively reflect the interaction of the cardiopulmonary and arterial baroreflexes which are key elements in the response to hypovolemic stress. These interactions which include an influence on the recruitment of unstressed volume, have not been adequately described quantitatively. Such a quantitative description would allow for the identification of key mechanisms and parameters in CVS short-term control and make possible the design of optimal algorithms to stabilize the CVS when a hypovolemic challenge occurs. This model will be directly applicable to the problem of developing strategies for analyzing and treating clinical problems that arise in CVS short-term control. During acute hypovolemia (due either to reduced or sequestered blood volume), venous return falls, affecting CVS function and leading to a drop in arterial pressure. A number of quick acting interdependent control mechanisms are recruited to maintain CVS function and restore pressure and their independent effects are not always consistent nor are their interactions always mutually supportive. This short-term control is the first stage of overall CVS system control. As hypovolemic stress persist mid-term and long-term (time-wise) controls are recruited as well. Control problems that arise that are closely connected to the mechanisms of blood volume and pressure control include stabilization of blood pressure during orthostasis, hemodialysis, and after acute hemorrhage. This project will utilize a wide range of clinical data reflecting a number of conditions. With our National Partners (NP) we plan to carry out a set of experiments to validate the model for healthy individuals. We also will have access to a large data base of CVS measurements reflecting dysfunction in various aspects of short-term control. This data provided by our NP will allow for the study of various interactions or isolation of control mechanisms. Such data provides the necessary data base for model validation and the model developed should represent an important improvement over current models that do not adequately address the nature of the interaction of the various control loops. Clinical application of the model revolves around a cluster of problems the common feature of which is short-term low blood volume challenge to cardiovascular stability. These include Orthostatic Intolerance and Postural Tachycardia Syndrome. The model developed in this project will quantify short-term blood volume and pressure control, and provide the analytical basis for a sensitivity analysis to reveal key parameters which will aid in devising submodels which will have direct near term clinical applications.

The objective of this project is to develop a physiologically based mathematical model of the cardiovascular system (CVS) that can be applied to study the short-term control of hypovolemic stress. The primary goal will be to develop a model that can quantitatively reflect the interaction of the cardiopulmonary and arterial baroreflexes which are key elements in the response to hypovolemic stress. These interactions which include an influence on the recruitment of unstressed volume, have not been adequately described quantitatively. Such a quantitative description would allow for the identification of key mechanisms and parameters in CVS short-term control and make possible the design of optimal algorithms to stabilize the CVS when a hypovolemic challenge occurs. This model will be directly applicable to the problem of developing strategies for analyzing and treating clinical problems that arise in CVS short-term control. During acute hypovolemia (due either to reduced or sequestered blood volume), venous return falls, affecting CVS function and leading to a drop in arterial pressure. A number of quick acting interdependent control mechanisms are recruited to maintain CVS function and restore pressure and their independent effects are not always consistent nor are their interactions always mutually supportive. This short-term control is the first stage of overall CVS system control. As hypovolemic stress persist mid-term and long-term (time-wise) controls are recruited as well. Control problems that arise that are closely connected to the mechanisms of blood volume and pressure control include stabilization of blood pressure during orthostasis, hemodialysis, and after acute hemorrhage. This project will utilize a wide range of clinical data reflecting a number of conditions. With our National Partners (NP) we plan to carry out a set of experiments to validate the model for healthy individuals. We also will have access to a large data base of CVS measurements reflecting dysfunction in various aspects of short-term control. This data provided by our NP will allow for the study of various interactions or isolation of control mechanisms. Such data provides the necessary data base for model validation and the model developed should represent an important improvement over current models that do not adequately address the nature of the interaction of the various control loops. Clinical application of the model revolves around a cluster of problems the common feature of which is short-term low blood volume challenge to cardiovascular stability. These include Orthostatic Intolerance and Postural Tachycardia Syndrome. The model developed in this project will quantify short-term blood volume and pressure control, and provide the analytical basis for a sensitivity analysis to reveal key parameters which will aid in devising submodels which will have direct near term clinical applications.