Obesity is increasing at an alarming rate in the United States and is a major risk factor for a variety of cardiovascular diseases. Obese humans have an impaired ability to increase muscle blood flow in response to exercise, and the mechanisms underlying this abnormal increase in blood flow (functional hyperemia) are unclear.
An impaired functional hyperemia could potentially prevent the obese patient from adequate exercise, a therapy known to improve glucose, lipids and weight control. Therefore, a better understanding of the mechanisms underlying improved functional hyperemia by chronic exercise training in obesity is important. Our published studies suggest that hyperglycemia and/or hyperlipidemia impair functional vasodilation through attenuated arachidonic acid mediated vasodilation.
We have demonstrated that chronic exercise training improves acute functional vasodilatory responses in an animal model of obesity, the obses Zucker rat. The mechanisms responsible for the improvement in vascular responses following an exercise training period are not known. Our current research is based on determining mechanisms by which functional hyperemia is impaired in obesity, and the mechanisms by which chronic exercise treatment improves vascular function. We use combinations of in vivo and in vitro microcirculatory and biochemical techniques to determine the mechanisms for the altered vascular responses in obesity.
Mathematical models and simulations have become an important tool in understanding the key causal relationships in normal and pathophysiological human processes. We have developed a comprehensive model of integrative human physiology called HumMod consisting of about 5000 variables describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. HumMod simulates the time-dependent evolution of body systems in physiological and pathological conditions. HumMod is comprised of a series of files describing the physiological variables, the mathematical relationships between them and the display characteristics of the simulations. HumMod.exe uses numerical methods for solving algebraic and differential equations, and generates screen updates and controls the simulation.
The physiological equations, variables, parameters and quantitative relationships as well as all other model details are described in XML text files. Model structure is based upon documented physiological responses from the peer-reviewed literature. Users can view time-dependent solutions and interactively alter parameters to investigate physiological responses. Pathophysiological states can be mimicked through the use of radiobuttons and sliderbars that allow alterations in basal physiological responses, such as cardiac contractility, renal artery stenosis, or altered hormone levels.
HumMod allows the user to provide clinical treatments, including pharmacological agents, placing the patient on a ventilator, administering IV fluids, or performing a blood transfusion. HumMod allows the user to adjust many characteristics of the patient’s physical environment, such as temperature, humidity, and barometric pressure. Additionally users can determine physiological responses in a more in-depth basis, particularly expanding physiological parameters that are not directly measurable.
HumMod contains a highly detailed representation of physiological and pathophysiological mechanisms and provides a rich environment for understanding human physiology. HumMod can be downloaded at http://hummod.org.
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