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Development of Capabilities for Simultaneous Assessment of Pulmonary and Systemic Hemodynamics in Conscious Rat to Identify Therapies with Pulmonary Selectivity
Author(s) -
Zhao Huawei,
Shen Xiaolan,
Hong Xuening,
Small Kersten,
Madwed Jeffrey
Publication year - 2015
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.29.1_supplement.647.7
Subject(s) - medicine , pulmonary artery , tadalafil , pulmonary hypertension , vascular resistance , cardiac output , hemodynamics , ascending aorta , cardiology , pulmonary artery catheter , aorta , sildenafil
Novel therapies for pulmonary arterial hypertension (PAH) that specifically dilate the pulmonary vasculature are desired. Our aim was to establish capabilities to monitor pulmonary and systemic pressures and cardiac output simultaneously in a conscious rat model of PAH to identify those therapies that show pulmonary selectivity. To achieve this capability, HD‐S21 dual pressure transmitters from Data Science International were surgically implanted to male Sprague‐Dawley rats with one catheter placed in the pulmonary artery and other in the abdominal aorta to measure pulmonary and systemic arterial pressure (PAP, SBP) simultaneously. Rats were also instrumented with flow probes (Transonic Systems Inc) around the ascending aorta to monitor cardiac output (CO) and to calculate intra‐rat pulmonary and systemic vascular resistance (PVR, SVR). Rats were exposed to hypoxia (10% O 2 ) for two weeks to create a clinically relevant PAH disease model. The increase in mean PAP was 18 ± 1 to 50 ± 2 mmHg which was mainly due to the increase in PVR (0.14 ± 0.01 to 0.57 ± 0.06) mmHg/ml/min. The methods were validated using Tadalafil, a standard PAH therapy inhibiting PDE 5 at 1, 3 and 10 mg/kg which showed dose dependent decreases in PAP and PVR to a greater extent than the SBP and SVR. In conclusion, innovative capabilities to determine PVR and SVR simultaneously have been established in conscious rodent which allows us to directly compare pulmonary and systemic hemodynamic activities in the same animal minimizing cross‐study variability with different cohort of animals. These methods have provided us with a powerful approach to identify therapies for PAHs with pulmonary selectivity.