Unloading the failing heart: An animal model for reverse remodeling by transient transverse aortic constriction

Aims: For some patients with end-stage heart failure, the temporary therapy with a left ventricular assist device (LVAD) may be the only clinical option. LVAD support may initiate „reverse remodeling“. We developed a mouse model with a reversible transverse aortic constriction (TAC) to mimic the effects of LVAD unloading after device implantation in patients with heart failure.

Methods: Minimally invasive TAC was performed in 14 mice using a novel tourniquet technique and 5 mice underwent sham operations. The band was removed twenty-one days later. Aortic doppler velocity gradients were measured to assess the degree of aortic constriction. Transthoracic echocardiography, LV catheterization and histology were used to evaluate cardiac function and remodeling due to TAC and after removal of the stenosis.

Results: The total operative mortality was 10%. Tourniquet banding of the transverse aortic arch resulted in an increase in aortic flow velocity and caused left ventricular hypertrophy, as evidenced by an increase in left ventricular posterior wall thickness (TAC 1.43±0.09mm vs. sham 1.19±0.14mm, n=14/5). TAC led to a reduced LV fractional shortening (TAC 23±1% vs. sham 31±3%, n=14/5, p<0.01). Three weeks after TAC, the tourniquet was successfully removed by a minimally invasive procedure without a second thoracotomy.

Conclusions: We have developed a surgical tourniquet model in mice to induce a transient increase in LV afterload by transverse aortic constriction. The reversibility of this technique – avoiding the need for a second invasive surgery with thoracotomy – allows us to study the process of reverse cardiac remodeling in mice.