Format

Send to

Choose Destination
Am J Physiol Heart Circ Physiol. 2019 Mar 1;316(3):H684-H692. doi: 10.1152/ajpheart.00573.2018. Epub 2018 Dec 21.

Right coronary artery ligation in mice: a novel method to investigate right ventricular dysfunction and biventricular interaction.

Author information

1
Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université de Montpellier, PhyMedExp, Montpellier , France.
2
Department of Anaesthesiology and Critical Care Medicine, Arnaud de Villeneuve Academic Hospital , Montpellier , France.
3
CiPharma, Escola de Farmácia, Universidade Federal de Ouro Preto , Minas Gerais , Brazil.
4
Aix-Marseille University, CNRS, Institut de Biologie du Développement de Marseille, Marseille , France.

Abstract

Right ventricular (RV) dysfunction can lead to complications after acute inferior myocardial infarction (MI). However, it is unclear how RV failure after MI contributes to left-sided dysfunction. The aim of the present study was to investigate the consequences of right coronary artery (RCA) ligation in mice. RCA ligation was performed in C57BL/6JRj mice ( n = 38). The cardiac phenotypes were characterized using high-resolution echocardiography performed up to 4 wk post-RCA ligation. Infarct size was measured using 2,3,5-triphenyltetrazolium chloride staining 24 h post-RCA ligation, and the extent of the fibrotic area was determined 4 wk after MI. RV dysfunction was confirmed 24 h post-RCA ligation by a decrease in the tricuspid annular plane systolic excursion ( P < 0.001) and RV longitudinal strain analysis ( P < 0.001). Infarct size measured ex vivo represented 45.1 ± 9.1% of the RV free wall. RCA permanent ligation increased the RV-to-left ventricular (LV) area ratio ( P < 0.01). Septum hypertrophy ( P < 0.01) was associated with diastolic septal flattening. During the 4-wk post-RCA ligation, LV ejection fraction was preserved, yet it was associated with impaired LV diastolic parameters ( E/ E', global strain rate during early diastole). Histological staining after 4 wk confirmed the remodeling process with a thin and fibrotic RV. This study validates that RCA ligation in mice is feasible and induces RV heart failure associated with the development of LV diastolic dysfunction. Our model offers a new opportunity to study mechanisms and treatments of RV/LV dysfunction after MI. NEW & NOTEWORTHY Right ventricular (RV) dysfunction frequently causes complications after acute inferior myocardial infarction. How RV failure contributes to left-sided dysfunction is elusive because of the lack of models to study molecular mechanisms. Here, we created a new model of myocardial infarction by permanently tying the right coronary artery in mice. This model offers a new opportunity to unravel mechanisms underlying RV/left ventricular dysfunction and evaluate drug therapy.

KEYWORDS:

cardiomyocytes; diastolic dysfunction; right ventricular infarction model

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center