Open AccessIsolated heart model demonstrates evidence of contractile and diastolic dysfunction in right ventricles from rats with sugen/hypoxia‐induced pulmonary hypertension
Author(s) -
NetoNeves Evandro M.,
Frump Andrea L.,
Vayl Alexandra,
Kline Jeffrey A.,
Lahm Tim
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13438
Subject(s) - pulmonary hypertension , diastole , medicine , apelin , cardiology , hypoxia (environmental) , ventricular pressure , pulmonary artery , pressure overload , right ventricular hypertrophy , muscle hypertrophy , blood pressure , chemistry , oxygen , cardiac hypertrophy , receptor , organic chemistry
Although extensively used for the study of left ventricular function, limited experience exists with the isolated heart model in the evaluation of right ventricular ( RV ) function. In particular, no published experience exists with this tool in sugen/hypoxia‐induced pulmonary hypertension (SuHx‐ PH ), a frequently used model of severe and progressive PH . We sought to characterize markers of RV contractile and diastolic function in SuHx‐ PH and to establish their relationship with markers of maladaptive RV remodeling. Hearts were excised from anesthetized Sprague Dawley rats with or without SuHx‐ PH and perfused via the aorta using a Langendorff preparation. We explored the Frank–Starling relationship of RV function ( RV developed pressure, d P /d t max , and d P /d t min ; all normalized to RV mass) by increasing RV end‐diastolic pressure ( RVEDP ) from 0 to 40 mmHg. Functional studies were complemented by quantification of RV pro‐apoptotic signaling (bcl2/bax), procontractile signaling (apelin), and stress response signaling (p38 MAPK activation). Pearson's correlation analysis was performed for functional and biochemical parameters. SuHx‐ RV s exhibited severe RV dysfunction with marked hypertrophy and decreased echocardiographic cardiac output. For any given RVEDP , SuHx‐ RV s demonstrated less developed pressure and lower d P /d t max , as well as less pronounced d P /d t min , suggestive of decreased contractile and diastolic function. SuHx‐ RV s exhibited decreased bcl2/bax ratios, apelin expression, and p38 MAPK activation. Bcl2/bax and apelin RNA abundance correlated positively with RV developed pressure and d P /d t max and negatively with d P /d t min . p38 MAPK activation correlated positively with RV developed pressure. We conclude that SuHx‐ RV s exhibit severe contractile and diastolic dysfunction. Increased pro‐apoptotic signaling and attenuated procontractile and stress response signaling may contribute to these functional alterations.