Abstract 15750: Neuregulin-1 Chronic Treatment Improves Right Ventricle Cardiomyocyte Function in Pulmonary Hypertension
This study evaluated the effects of neuregulin (NRG)-1 chronic treatment on intrinsic myocardial properties, namely on the modulation of active and passive force of cardiomyocytes isolated from the right ventricle (RV) of animals with pulmonary arterial hypertension (PAH).
Male Wistar rats (180-200g) randomly received monocrotaline (MCT,60mg/Kg,sc) or vehicle. After 14 days, animals were randomly assigned to receive treatment with either NRG-1 (40ug/Kg/day,ip) or vehicle. The study resulted in 4 experimental groups: control (CTRL, n=16); CTRL+NRG (n=15); MCT (n=13); MCT+NRG (n=18). Twenty one to 24 days after MCT administration, samples were collected for functional studies. RV samples were mechanically disrupted and incubated in relaxing solution supplemented with Triton (0.2%). Cardiomyocytes were subsequently attached with silicone adhesive between a force transducer and a piezoelectric motor and active and passive forces were measured. Only significant results (p<0.05) are given.
MCT-group isolated cardiomyocytes developed higher passive force when compared to CTRL-group cells at the sarcomere lengths of 2.0 (MCT vs. CTRL: 1.90±0.43 vs. 1.43±0.29N/m2), 2.2 (MCT vs. CTRL: 3.66±0.69 vs. 2.68±0.24N/m2), and 2.3μm (MCT vs.
CTRL: 5.76±1.15 vs. 3.86±0.87N/m2). NRG-1 treatment restored passive force to levels similar to the CTRL-group cardiomyocytes, at 2.0, 2.2, and 2.3μm (MCT+NRG: 1.28±0.25, 3.04±0.55, and 3.63±0.89N/m2, respectively). CTRL+NRG-group cardiomyocytes developed significantly less passive force when compared to CTRL-group cells (CTRL+NRG: 1.16±0.31, 2.27±0.38, and 3.05±0.54N/m2, at 2.0, 2.2, and 2.3μm respectively). In the MCT+NRG-group cardiomyocytes active force development was decreased when compared to MCT-group cells (MCT vs MCT+NRG: 14.14±5.94 vs 9.67±2.83N/m2).
NRG-1 chronic treatment reverses the changes in both active and passive myocardial forces that occur in the presence of PAH. Interestingly, NRG-1 chronic treatment also decreases the passive force and thus myocardial stiffness of cardiomyocytes isolated from healthy animals. These findings show that NRG-1 pathway regulates both systolic and diastolic function at the cellular level, suggesting a therapeutic role of this pathway in PAH.
- © 2013 by American Heart Association, Inc.