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11,12 Two retrospective studies of the use of sildenafil in dogs with pulmonary hypertension indicate that sildenafil has potential http://www.selleckchem.com/products/bay-57-1293.html therapeutic efficacy.4,13 The aim of this study is to prospectively evaluate the effect of sildenafil on pulmonary arterial pressure, exercise capacity, and QOL (as assessed by owners) in dogs with PAH. This was a randomized, placebo controlled, double-blind, crossover study. Dogs with PAH were eligible for enrollment after informed client consent had been obtained. Echocardiography was performed by a board certified or board eligible cardiologist (E.D. or M.M.S.) using a Sonos 7500 (Philips Medical Imaging; Andover, MA). A complete echocardiogram was obtained at each time point, including 2D, M-mode, and Doppler echocardiography. The tricuspid valve was imaged in the short and long axis views as well as obliquely to find the optimal (most parallel to the transducer beam) signal for Doppler measurement. The systolic pressure gradient (PGs) was estimated using the modified Bernoulli equation (PGs = 4V2 where V is the maximal flow velocity across the tricuspid valve). Dogs were included if their PGs was at least 60?mmHg. The pulmonic valve was also interrogated to be certain that there was no evidence of pulmonic stenosis. Dogs were excluded if they had concurrent radiographic evidence of pulmonary edema consistent with left-sided congestive heart failure, or they had systemic hypertension/hypotension (>180?mmHg or http://www.selleck.cn/products/CAL-101.html made before the study were permitted, dogs were excluded if angiotensin converting enzyme inhibitors or phosphodiesterase inhibitors had been added to the treatment regimens within the prior 4 weeks. This study was approved by the Animal Care and Use Committee at the University of Pennsylvania. Dogs were evaluated 3 times during the study: a baseline evaluation at enrollment (0 weeks), a 2nd evaluation after the 1st treatment phase (4 weeks), and a 3rd evaluation after the 2nd treatment phase (8 weeks). At the baseline evaluation the following were performed: echocardiogram, thoracic radiographs, arterial blood gas analysisa (including electrolytes, http://www.selleckchem.com/products/gsk2126458.html lactate concentration, and hematocrit) and systemic arterial blood pressure (SABP; as measured by Doppler). A watch-sized activity monitorb was placed on a collar and positioned ventrally on the neck of each dog for the duration of the study. The monitor continuously measured the intensity, frequency, and duration of movement by generation of a voltage from a piezoelectric sensor that is then converted to a raw activity value. Data was downloaded from the monitor after each phase of the study and converted to an activity count per minute using associated computer software. A detailed description of this device can be found elsewhere.14,15 QOL was assessed with a questionnaire (QOL1) at each of the 3 patient evaluations.