Longitudinal Cardiovascular Magnetic Resonance Evaluation of Progressive Pressure Overload Due to O-ring Induced Ascending Aortic Constriction in Rats.

Abstract

Background: Aortic stenosis is a debilitating disease characterized by pressure overload and development of myocardial fibrosis. Animal models that mimic this disease are crucial for translational research. Aortic constriction in rats is commonly used to induce pressure overload, but the precise disease progression in the O-ring induced model of ascending aortic constriction has not been thoroughly evaluated. Additionally, identifying early imaging biomarkers that can predict fibrosis could enhance the model's translational relevance. This study aims to evaluate a rat model of progressive pressure overload using cardiovascular magnetic resonance imaging (CMR) by investigating the degree of constriction at different time points and identifying early imaging biomarkers predicting myocardial fibrosis at later stages.

Methods: Sprague Dawley rats (n=14) underwent aortic banding with O-rings (inner diameter of 1.5mm or 1.3mm). Sham-operated rats (n=8) served as controls. CMR was performed every fourth week until 20 weeks post-surgery, followed by tissue harvesting and measurements of fibrosis with histology.

Results: All banding groups gradually developed left ventricular (LV) hypertrophy, impaired LV diastolic function (increased E/SRe), increased left atrial (LA) size, and impaired LA function (reduced LA ejection fraction and peak LA strain), but preserved LV ejection fraction during the course of study. The tightest constriction exhibited increased LV fibrosis at 20 weeks. LA diameter at 4 weeks independently predicted LV myocardial fibrosis.

Conclusion: This animal model mimics the gradual progression of stenosis seen in humans, highlighting its translational potential. Early LA diameter predicted myocardial fibrosis. These findings underscore the model's relevance for studying disease progression in LV pressure overload.