INTRODUCTION Pulmonary vascular input impedance has been increasingly promoted as an important diagnostic for pulmonary arterial hypertension (PAH) The human studies noted above have understandably not examined detailed associations between impedance and vascular behavior and structure, since the latter data are obtainable only through focused drug studies or ex-vivo measurements. Mechanical changes to a vascular network should be reflected in its input impedance; thus, such investigation should be useful in determining how impedance varies with changes in vascular condition, such as chronic stiffening due to vascular remodeling or acute stiffening due to smooth muscle cell response and/or pressure-induced strain-stiffening. Naturally, clinical identification of such stiffness changes on a routine basis could greatly impact diagnosis. Here, we demonstrate simple-toimplement impedance measurements in two animal models as part of a larger effort to establish said links between clinically-viable diagnostics, such as impedance, and physiological changes that occur to the vasculature as part of the progression of PAH. METHODS Animal Preparation: The two animal models examined here develop PAH due to chronic exposure to a hypoxic environment. The first model consisted of 10 male Sprague-Dawley rats (300-400g), half exposed to hypoxia via hypobaric chamber for 3-4 weeks (barometric pressure ≈ 410 mmHg) and half retained at standard conditions in Denver, CO (barometric pressure ≈ 630 mmHg). The second model utilized 4 male Holstein calves (70-110lb), again with half exposed to hypoxia for two weeks (barometric pressure ≈ 460 mmHg) and the other half remaining normoxic. Both models were exposed to a 12:12-h light-dark cycle, and water and appropriate food were made available ad libitum. Animal care and use committees at both the University of Colorado Health Science Center (rat) and Colorado State University (calf) approved all protocols and procedures. Animal Data Collection and Analysis: The measurements obtained from each animal are identical; the main differences between collection methods are equipment size and type. For all measurements, rats are anesthetized with ketamine hydrochloride (40 mg/kg) and xylazine (10 mg/kg) intraperitoneally, while cows remain conscious. Right jugular access is then obtained in each animal, and a fluid filled catheter, consisting of PV1 tubing for the rat or a commercial Swan-Ganz catheter for the calf, is inserted into the main pulmonary artery (MPA) for pressure measurements. During collection of MPA pressure, blood velocity at the midline of the MPA is obtained with pulse-wave Doppler echocardiography using an FPA probe on a commercial ultrasound scanner (Vivid 5, GE Medical Systems Inc). The imaging depth dictates the probe frequency
