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

Right ventricular (RV) dysfunction can lead to complications following acute inferior myocardial infarction (MI). However, it is unclear how RV failure after MI contributes to left-sided dysfunction is unclear. The aim of this 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 weeks post-RCA ligation. Infarct size was measured using 2,3,5-triphenyltetrazolium chloride (TTC)-staining 24h post-RCA ligation and the extent of the fibrotic area was determined 4 weeks after MI. RV dysfunction was confirmed 24h 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 RV free wall. RCA permanent ligation increased RV/LV area ratio (p<0.01). Septum hypertrophy (p<0.01) was associated with diastolic septal flattening. During the 4 weeks post-RCA ligation, the 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 weeks confirmed the remodelling process with a thin and fibrotic RV. This study validates that RCA ligation in mice is feasible and induces right ventricular heart failure associated with development of LV diastolic dysfunction. Our model offers a new opportunity to study mechanisms and treatments of RV/LV dysfunction after MI.