A modified murine model for the study of reverse cardiac remodelling.

Abstract

Background: The authors previously reported a murine model of left ventricular hypertrophy (LVH) and regression using a suture technique of transverse aortic arch constriction and subsequent removal. A number of issues have limited the widespread adoption of this method. The present study assessed a modification of this model using a titanium clip.

Methods: Male C57BL/6 mice (n=95) underwent minimally invasive aortic banding for three, four or six weeks with or without subsequent band removal for one week. Hearts were evaluated both structurally and functionally using heart weight/body weight ratios, transthoracic echocardiography and direct left ventricular pressure measured using catheterization.

Results: Clip banding resulted in a threefold gradient across the transverse aortic arch. Pressure overload induced concentric LVH by three weeks that progressively decompensated. By six weeks, hearts were significantly dilated, with poor left ventricular function. Clips were removed in a minimally invasive procedure after each time point. When overloaded for either three or four weeks, removal of the clip with subsequent pressure relief enabled regression of LVH and restoration of function. When removed after six weeks of banding, mouse hearts were unable to reverse remodel and maintained elevated left ventricular end-diastolic pressures and lung congestion.

Conclusions: The application and removal of a titanium clip successfully induced pressure overload and relief associated with the serial development and reversal of LVH. Compared with similar models using suture ligation and release, this method was found to be a simple, effective (no slipped bands) and reproducible method to study murine LVH, heart failure and its regression.