Unveiling gender differences in demand ischemia: a study in a rat model of genetic hypertension

Abstract

In the pressure overload model of the Dahl salt-sensitive rat, female gender is associated with a more pronounced concentric hypertrophy, whereas male hearts develop a more eccentric type of remodeling. Although present at baseline, after ischemia/reperfusion systolic function is gender-independent but more determined by hypertrophy. In contrast, diastolic function is gender-dependent and aggravated by hypertrophy, leading to pronounced diastolic dysfunction. We can conclude that in the malignant setting of demand ischemia/reperfusion gender differences in hypertrophied hearts are unmasked: female hypertrophied hearts are more susceptible to ischemia/reperfusion than males. To determine whether in female hypertensive patients with acute coronary syndromes, diastolic dysfunction could contribute to the worse clinical course, further experimental and clinical studies are needed.

Salt loading exacerbates diastolic dysfunction and cardiac remodeling in young female Ren2 rats

“…Others have shown similar findings in regards to sex-specific effects on hypertrophy in models of pressure overload, post-ischemic models, and Ang II-infused models [37–39]. In the model of ascending aortic banding of gradually induced pressure overload, female rats demonstrated a concentric hypertrophy with preservation of LV mass and systolic function not seen in males [38].…”

“…This, coupled with differences in sex-specific biomechanical properties such as pulsatile arterial loading and increases in wave reflection due to increases in body size contribute directly to differences in adaptation to increases in afterload on LVH in obese women [35,36]. Work done in the Dahl salt-sensitive rat suggests that development of diastolic dysfunction in female rats was dependent on a hypertrophied left ventricle, whereas males under the same conditions did not exhibit any impairments in the pressure-volume relationship [37]. This suggests sex-specifics effects on LVH and remodeling that precondition for diastolic dysfunction.…”

The Effects of Biological Sex and Diet on the Development of Heart Failure

“…Although the degree of cardiac hypertrophy is similar in both females and males, females undergo concentric hypertrophy with no additional cavity dilation, whereas males experience eccentric hypertrophy and ventricular cavity dilation. 29,30 Accordingly, these females demonstrate elevated contractile function compared with males. Moreover, using a high-salt diet to induce pressure overload illustrates how dietary intake can influence cardiac remodeling and the development of heart failure in a sex-dependent manner.…”

Basic and applied research at the department of cardio-thoracic surgery: work in progress

“…The third area of research, gender differences in cardiovascular disease, has caught our attention, when we realized that female gender is associated with higher mortality in ischemic cardiomyopathy. In a recent publication we were able to show that already during compensated hypertrophy female gender is more susceptible to ischemia and reperfusion [38,39]. In current studies we have been following gender differences in the development of heart failure at different stages of disease.…”