Congenital heart disease and right ventricular failure – The passive vs. the active components in diastolic dysfunction.

Wiechen, M.P.H. van (2014) Congenital heart disease and right ventricular failure – The passive vs. the active components in diastolic dysfunction. thesis, Medicine.

Text WiechenvanM.pdf Restricted to Registered users only Download (1MB)

Abstract

Objective: Right ventricular failure/cor pulmonale (RVF) is often seen in end-stage pulmonary arterial hypertension (PAH) and has a bad prognosis. A long-existing pressure load on the right ventricle (RV) leads to hypertrophy and finally to failure. Previous results suggest that RVF is caused by diastolic dysfuncton. The goal of this study is to investigate whether diastolic dysfunction is mainly caused by a change in passive stiffness or by a change in active relaxation. Design: Tissue of 2 existing animal models was collected and used for experimental research. One of the two models consisted of rats that underwent pulmonary artery banding (PAB) leading to an increased pressure load on the RV. Rats were then assessed on clinical symptoms of failure. In the other model the influence of sildenafil treatment on PAB was investigated. With the use of RT-PCR, western blot and ELISA; mechanisms of diastolic function were investigated. We looked at the sodium-calcium transporter (NCX), phospholamban (PLN), SERCA2, titin isoforms (N2Ba, N2B) and protein kinases A and G activity. (PKA, PKG) Results: Components determining passive stiffness are changed. Less fibrosis and an increase of the N2Ba/N2B ratio: both theoretically leading to a less stiff myocardium. The active components are differentially affected: SERCA2 expression decreased and PLN expression increased with declining diastolic function, NCX remained unchanged. PKA activity was decreased in the banded animals vs. control. PKG1 activity was unchanged. Conclusion: In this study we show that diastolic dysfunction is associated with decreased active relaxation and a changed stiffness through a decrease in fibrosis and increase in the compliant titin isoform.

Item Type:	Thesis (Thesis)
Supervisor name:	Berger, Prof. dr. R.M.F. and Bartelds, Dr. B.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:38
Last Modified:	25 Jun 2020 10:38
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/26

Actions (login required)

View Item