Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload

Abstract

Objectives: To identify gender differences in left ventricular remodeling, hypertrophy, and function in response to pressure overload due to ascending aortic banding in rats.

Background: Gender may influence the adaptation to pressure overload, as women with aortic stenosis have greater degrees of left ventricular hypertrophy and better left ventricular function than men.

Methods: Fifty-two weanling rats underwent ascending aortic banding (16 males, 18 females), or sham surgery (9 males, 9 females). At 6 and 20 weeks, rats underwent transthoracic echo Doppler studies, and closed-chest left ventricular pressures with direct left ventricular puncture. Perfusion-fixed tissues from eight rats were examined morphometrically for myocyte cross-sectional area and percent collagen volume.

Results: At 6 weeks after aortic banding, left ventricular remodeling, extent of hypertrophy, and function appeared similar in male and female rats. At 20 weeks, male but not female rats showed an early transition to heart failure, with onset of cavity dilatation (left ventricular diameter=155% vs. 121% of same-sex sham), loss of concentric remodeling (relative wall thickness=102% vs. 139% of sham), elevated wall stress (systolic stress=266% vs. 154% of sham), and diastolic dysfunction (deceleration of rapid filling=251% vs. 190% of sham). Left ventricular systolic pressures were higher in female compared with male rats (186+/-20 vs. 139+/-13 mm Hg), while diastolic pressures tended to be lower (14+/-4 vs. 17+/-4 mm Hg).

Conclusions: Gender significantly influences the evolution of the early response to pressure overload, including the transition to heart failure in rats with aortic stenosis.