Abstract
Introduction
This study aims to determine whether changes in right ventricular (RV) cardiomyocyte contractile apparatus are involved in RV failure secondary to pulmonary arterial hypertension (PAH).
Methods
- Maximal force and passive stiffness were determined in membrane-permeablized RV cardiomyocytes isolated from RV tissue obtained after heart-lung transplantation of PAH-patients and non-failing donors. Maximal force was measured at maximal Ca2+-activation, while cardiomyocyte passive stiffness in relaxing solution (low Ca2+ concentration).
- The role of β-Adrenergic receptor signaling on cardiomyocyte passive stiffness was mimicked by determining passive stiffness after PKA incubation.
Results
- No significant differences were found in cardiomyocyte maximal force in PAH patients and donors.
- Passive stiffness was significantly increased at all sarcomere lengths in PAH patients compared to donors.
- PKA incubation partially restored RV cardiomyocytes passive tension in PAH patients to donor values.
Conclusions
Our study demonstrates increased RV cardiomyocytes passive stiffness in PAH patients, partially restored by PKA incubation. This finding suggests that reduced β-adrenergic receptor signaling plays an important role in the development of RV diastolic stiffness in PAH patients.
- © 2012 ERS
