An Optimized Model of Hypertrophic Preconditioning Confers Cardioprotection in the Mouse

Abstract

Background: Conventional models of hypertrophic preconditioning (C-HP) can be established surgically through transverse aortic constriction (TAC) → deconstriction (De-TAC) → reconstriction (Re-TAC) characterized by dynamic afterload while it exerts technical difficulty on operators and poses high mortality during perioperative period in mice. We aimed to introduce an optimized method for obtaining a hypertrophic preconditioning (O-HP) model for further study on cardiac hypertrophy.

Methods: Ninety mice were divided into four groups: sham, TAC, C-HP, and O-HP. The sham group was exerted on three-time thoracotomies. The TAC group experienced twice thoracotomies and one TAC operation. C-HP and O-HP groups were given TAC, De-TAC, and Re-TAC operation at day 0, day 3, and day 7 in conventional and optimized method, respectively. We optimized the operating procedure in O-HP mice compared with the C-HP group by (1) leaving a ∼3-cm suture fixed in the subcutaneous layer after aortic constriction in TAC surgery (2) using two small forceps to untie the constriction knot instead of cutting it in the De-TAC operation. Ultrasound biomicroscopy was used for hemodynamics and cardiac function detection. Four weeks after the third surgery, all mice were sacrificed and pathology was analyzed among four groups.

Results: Four weeks after Re-TAC, the survival of O-HP mice was 63.3% while that of C-HP was 26.7%. Ultrasound biomicroscopy showed a successful establishment of HP models. C-HP and O-HP mice had improved cardiac structure and function indicated by left ventricular end-systolic diameter, left ventricular end-systolic posterior wall thickness, left ventricular ejection fraction, and left ventricular fractional shortening than the TAC group. Pathological analysis showed O-HP as well as C-HP had less hypertrophy than the TAC mice.

Conclusions: Our results provide a rapid, safe, efficient, and reproducible method for optimized establishment of the HP model, which will facilitate studies for early intervention and prevention of left ventricular hypertrophy and heart failure.

Keywords: Cardiac hypertrophy; Hypertrophic preconditioning; Optimized model; Transverse aortic constriction; Ultrasound biomicroscopy.