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Hsp90 inhibition prevents monocrotaline‐induced pulmonary hypertension in rats, as revealed by high resolution echocardiography
Author(s) -
Dimitropoulou Christiana,
Meadows Louise,
Su Yunchao,
Litwin Sheldon,
Catravas John D
Publication year - 2012
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.26.1_supplement.873.17
Subject(s) - ventricle , pulmonary hypertension , medicine , cardiology , ventricular pressure , high resolution , cardiac index , cardiac output , blood pressure , remote sensing , geology
Four weeks after a single sc injection of monocrotaline (MCT; 60mg/kg), rats develop pathologic changes resembling those of human pulmonary arterial hypertension (PAH). Using high resolution echocardiography, we investigated non‐invasively, the ability of the hsp90 inhibitor 17‐AAG (10 mg, 3x weekly) to prevent the effects of MCT. PA flow velocity time integral (VTI), PA acceleration time (PAT), cardiac index (CI) and cardiac output (CO) values were reduced in rats treated with MCT alone, indicative of PAH. 4‐ or 2‐week (starting at week 3 after MCT) treatment with 17‐AAG prevented the decrease in VTI and PAT, but not in CO and CI. Right ventricle (RV) free wall (RVFW) thickness also increased with MCT, but not in the 4‐week 17‐AAG treatment group. Invasive assessment of right ventricular pressure (RVP) at the end of the 4‐week treatments confirmed increased RVP in the MCT, but not in the 17‐AAG treated animals. We conclude that treatment with hsp90 inhibitor for all or part of the 4‐week exposure to MCT effectively prevents the initiation/progression of PAH and that high resolution echocardiography is a useful tool for the non‐invasive, real‐time, repeated evaluation of cardiopulmonary changes in this model of PAH. (Supported by the AHA).