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We have developed Quantitative Circulatory Physiology (QCP), a mathematical model of integrative human physiology containing over 4,000 variables of biological interactions. This model provides a teaching environment that mimics clinical problems encountered in the practice of medicine. The model structure is based on documented physiological responses(More)
Over the last 10 years, 'Systems Biology' has focused on the integration of biology and medicine with information technology and computation. The current challenge is to use the discoveries of the last 20 years, such as genomics and proteomics, to develop targeted therapeutical strategies. These strategies are the result of understanding the aetiologies of(More)
This study examined interactions between adenosine (Ado) and angiotensin II (ANG II) in controlling renal blood flow (RBF) and glomerular filtration rate (GFR). In six normal dogs, intrarenal Ado infusion (1.0 mumol/min) transiently decreased RBF, but during sustained Ado infusion RBF increased to 122 +/- 7% of control, although GFR remained at 75 +/- 6% of(More)
Time course of multiple hemodynamic changes in rats after opening an AV fistula was assessed. The fistula was made in male Sprague-Dawley rats by anastomosing the aorta and vena cava below the renal arteries. At 1 h (1H), 1 day (1D), 1 wk (1W) and 5 wk (5W) in sham controls or after opening an AV fistula, we measured cardiac output (CO) and tissue flows by(More)
Obesity, insulin resistance, dyslipidemia, and hypertension are components of the pathophysiological state known as metabolic syndrome. Adrenergic vasoconstriction is mediated through increases in cytosolic Ca2+ and the myofilaments' sensitivity to Ca2+. In many pathophysiological states, there is an enhanced role for Rho kinase (ROK)-mediated increases in(More)
Mathematical models and simulations are important tools in discovering key causal relationships governing physiological processes. Simulations guide and improve outcomes of medical interventions involving complex physiology. We developed HumMod, a Windows-based model of integrative human physiology. HumMod consists of 5000 variables describing(More)
This study was designed to determine the physiological role of endothelium-dependent nitric oxide (EDNO) in the control of arteriolar diameter during rest and muscle stimulation. Diameters of first-, second-, and third-order arterioles in the superfused hamster cremaster muscle were measured before and throughout 1 min of field stimulation before and after(More)
The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min.(More)
OBJECTIVE In vitro superoxide activates pulmonary endothelial TRPM2 channels and increases Kf . We hypothesized that pulmonary capillary Kf is increased in a model of type I diabetes due to elevated vascular superoxide and resultant TRPM2 channel activation. METHODS Type I diabetes was induced in Zucker rats using STZ. Half of the STZ animals were treated(More)
This study was designed to determine the importance of the venular endothelium in the vasodilation of adjacent arterioles during functional hyperemia. The hamster cremaster muscle was prepared for in vivo microscopy. Two silver-silver chloride electrodes were placed across the pedicle of the cremaster muscle, and a square-wave pulse (10 V amplitude, 1 ms(More)