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Development of Capabilities for Simultaneous Measurement of Pulmonary and Systemic Pressure to Support Evaluation of Pulmonary Hypertension Therapies
Author(s) -
Zhao Huawei,
Sun ShuYu,
Shen Xiaolan,
Hong Xueninh,
Yang Liming,
Ping Xiaoli,
Wang Bo,
Davis Christopher A,
Metzger Joseph M,
Small Kersten M,
Madwed Jeffrey B
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb608
Subject(s) - medicine , sildenafil , pulmonary artery , pulmonary hypertension , tadalafil , cardiology , blood pressure , systemic inflammation , hemodynamics , hypoxia (environmental) , inflammation , chemistry , oxygen , organic chemistry
Pulmonary arterial hypertension (PAH) is a life threatening disease with few proven treatment options. It is important that new therapies directed at decreasing pulmonary pressure demonstrate vascular selectivity on the pulmonary bed over the systemic bed. Therefore, we establised methods to directly measure pulmonary arterial pressure (PAP) and systemic blood pressure (systemic BP) simultaneously in conscious freely moving rats using novel HD‐S21 dual pressure transmitters from DSI. Transmitters were implanted in normotensive male Sprague Dawley rats, with one catheter of transmitter placed in the pulmonary artery and the other in abdominal aorta. To create a more clinically relevant PAH model and to increase the assay window, rats were exposed to hypoxic conditions (10% O2) over two weeks which increased baseline sPAP from ~25 mmHg to ~80 mmHg, with minimal effects on systemic BP. Validation studies were performed using standard of care PAH therapies: Tadalafil and Sildenafil (PDE5 inhibitors). Both compounds had similar maximal effect on systolic PAP (sPAP) reduction (~18–22 mmHg) and modest effects on the systemic BP (10–15 mmHg) on hypoxia‐induced PAH. In conclusion, innovative capabilities to directly measure PAP and systemic BP simultaneously have been established in conscious freely moving rat, and these methods provide a powerful approach to directly compare pulmonary vs. systemic hemodynamic activities minimizing cross‐study variability with different cohort of animals and to identify PAH therapies that demonstrate pulmonary selectivity.