Gender Differences in Cardiac Dysfunction and Remodeling due to Volume Overload

Background: This study examined the sex differences for hemodynamic and echocardiographic changes in hypertrophied and failing hearts induced by arteriovenous (AV) shunt. Methods and Results: Echocardiographic and hemodynamic alterations were determined in male and female rats at 4 and 16 weeks after AV shunt. Ovariectomized females treated with estrogen for 16 weeks post-AV shunt were also used. Both genders developed cardiac hypertrophy at 4 and 16 weeks post-AV shunt; however, the increase in cardiac muscle mass was greater in females than males at 16 weeks. At 4 weeks post-AV shunt, increases in ventricular dimensions and left ventricular end-diastolic pressure (LVEDP) as well as a decrease in fractional shortening occurred in males only. Unlike the females, the rates of pressure development (+dP/dt) and decay (-dP/dt) were depressed and LVEDP increased in male rats at 16 weeks post-AV shunt. An increase in cardiac output was seen in both genders, but this was more marked in the males at 4 and 16 weeks post-AV shunt. Although mRNA levels for ACE were increased in both male and female rats at 4 and 16 weeks, mRNA levels for angiotensin II type 1 receptor were increased in males at 16 weeks only. Furthermore, increases in plasma catecholamines were elevated in males but were decreased or unchanged in females at 16 weeks of AV shunt. LV internal diameters as well as depressed fractional shortening occurred in males whereas increases in posterior wall thickness were seen in the female rats at 16 weeks of AV shunt. Ovariectomy resulted in depressed +dP/dt, -dP/dt, and fractional shortening, whereas a marked increase in cardiac output as well as increased LVEDP and LV internal diameters were observed at 16 weeks post-AV shunt. Although treatment with 17-beta estradiol normalized +/- dP/dt, LVEDP remained elevated. Conclusion: Gender differences in cardiac function may be clue to differences in the type of cardiac remodeling as a consequence of AV shunt. Furthermore, estrogen appears to play an important role in preventing cardiac dysfunction and adverse ventricular remodeling in female rats. (J Cardiac Fail 2010:16439-449)