Cardioprotection in female rats subjected to chronic volume overload: synergistic interaction of estrogen and phytoestrogens

2008 ◽  
Vol 294 (1) ◽  
pp. H198-H204 ◽  
Author(s):  
Jason D. Gardner ◽  
Gregory L. Brower ◽  
Tetyana G. Voloshenyuk ◽  
Joseph S. Janicki

Intact female rats fed a high-phytoestrogen diet are protected against adverse left ventricular (LV) remodeling induced by chronic volume overload. We hypothesized that both phytoestrogens and ovarian hormones, particularly estrogen, are necessary for this dietary-induced cardioprotection. To test this hypothesis, eight groups of female rats were studied; rats were fed either a high-phytoestrogen (+phyto) or phytoestrogen-free diet. Groups included sham-operated rats, intact rats with fistula (Fist), ovariectomized rats with fistula (Fist-OX), and Fist-OX rats treated with estrogen (EST). Myocardial function and remodeling were assessed after 8 wk of volume overload using a blood-perfused isolated heart apparatus. Fist-OX rats developed significant ventricular dilatation and increased compliance vs. intact Fist rats, which were associated with a significant decrease in contractility. Estrogen treatment prevented pulmonary edema and attenuated LV hypertrophy and dilatation but did not maintain contractility. However, dietary phytoestrogens completely prevented LV dilatation in both the Fist+phyto and Fist-OX+EST+phyto groups but had no effect on LV remodeling in the Fist-OX+phyto group. Contractility was significantly greater in the estrogen-treated rats fed the phytoestrogen diet than in those treated with estrogen alone. Dietary phytoestrogens did not affect LV or uterine mass, serum estrogen, LV estrogen receptor expression, or cardiac function in sham animals. These data indicate that estrogen is not solely responsible for the cardioprotection exhibited by intact females and that phytoestrogens can work synergistically with ovarian hormones to attenuate ventricular remodeling induced by chronic volume overload in female rats.

2005 ◽  
Vol 99 (4) ◽  
pp. 1378-1383 ◽  
Author(s):  
Jason D. Gardner ◽  
Gregory L. Brower ◽  
Joseph S. Janicki

Previously, we demonstrated that intact female rats fed a standard rodent diet containing soybean products exhibit essentially no adverse left ventricular (LV) remodeling in response to aortocaval fistula-induced chronic volume overload. We hypothesized that phytoestrogenic compounds in the diet contributed to the female cardioprotection. To test this hypothesis, four groups of female rats were studied: sham-operated (Sham) and fistula (Fist) rats fed a diet with [P(+)] or without [P(−)] phytoestrogens. Eight weeks postfistula, systolic and diastolic cardiac function was assessed by using a blood-perfused, isolated heart preparation. High-phytoestrogen diet had no effect on body, heart, and lung weights, or cardiac function in Sham rats. Fistula groups developed LV hypertrophy, which was not reduced by dietary phytoestrogens [1,184 ± 229 mg Fist-P(−) and 1,079 ± 199 mg Fist-P(+) vs. 620 ± 47 mg for combined Sham groups, P < 0.05]. Unstressed LV volume increased in Fist-P(−) rats (428 ± 16 vs. 300 ± 14 μl Sham, P < 0.0001), but it was not different from Sham for Fist-P(+) animals (286 ± 17 μl). Fist-P(−) rats developed increased ventricular compliance (5.3 ± 0.8 vs. 2.3 ± 0.3 μl/mmHg Sham, P < 0.01), whereas Fist-P(+) rats had no change in compliance (2.8 ± 0.4 μl/mmHg). Intrinsic ventricular contractility was maintained in the Fist-P(+) rats, but it was reduced ( P < 0.001) in the Fist-P(−) rats [systolic pressure-volume slope: 1.04 ± 0.03, 0.60 ± 0.06, and 0.99 ± 0.08 mmHg/μl, for Fist-P(+), Fist-P(−), and Sham, respectively]. These data indicate that dietary phytoestrogens contribute significantly to female cardioprotection against volume overload-induced adverse ventricular remodeling and that studies evaluating gender differences in cardiovascular remodeling must consider the influence of dietary phytoestrogens.


2017 ◽  
Vol 312 (1) ◽  
pp. H98-H105 ◽  
Author(s):  
M. C. El Hajj ◽  
V. K. Ninh ◽  
E. C. El Hajj ◽  
J. M. Bradley ◽  
J. D. Gardner

We have previously demonstrated the cardioprotective effects of ovarian hormones against adverse ventricular remodeling imposed by chronic volume overload. Here, we assess the estrogen receptor dependence of this cardioprotection. Four groups of female rats were studied: sham-operated (Sham), volume overloaded [aortocaval fistula (ACF)], Sham treated with estrogen receptor antagonist ICI 182,780 (Sham + ICI), and ACF treated with ICI. Cardiac function was assessed temporally using echocardiogram, and tissue samples were collected at 5 days and 6 wk postsurgery. All rats with volume overload had significantly increased cardiac output (96 ± 32 ml/min for ACF and 108 ± 11 ml/min for ACF + ICI vs. 31 ± 2 for Sham, P < 0.05). At 6 wk, volume overload induced significant left ventricular (LV) hypertrophy in both untreated and treated ACF groups. Both ACF groups developed significantly increased LV end-diastolic diameter (LVEDD), indicating LV dilatation, with the ACF + ICI group having the greatest increase (340%, relative to Sham). Ejection fraction was significantly reduced in the ACF + ICI group (23% reduction) at 6 wk postsurgery compared with untreated ACF ( P < 0.05). Interstitial collagen staining was significantly reduced by volume overload, with estrogen receptor antagonism causing greater collagen loss at both 5 days and 6 wk postsurgery. Furthermore, volume overload induced a significant increase in LV wall stress only in rats treated with estrogen antagonist. These data indicate that estrogen receptor signaling is essential for sex hormone-dependent cardioprotection against adverse remodeling. The maintenance of myocardial extracellular matrix collagen appears to play a key role in this cardioprotection. NEW & NOTEWORTHY We assessed the estrogen receptor (ER) dependence of female-specific cardioprotection using a rat model of chronic volume-overload stress. ER antagonism worsened ventricular wall stress, ventricular dilation, and cardiac dysfunction induced by volume overload. Further, blocking ERs resulted in cardiac remodeling and functional changes similar to that previously found in ovariectomized rats.


1996 ◽  
Vol 271 (5) ◽  
pp. H2071-H2078 ◽  
Author(s):  
G. L. Brower ◽  
J. R. Henegar ◽  
J. S. Janicki

The left ventricle (LV) significantly dilates and hypertrophies in response to chronic volume overload. However, the temporal responses in LV mass, volume, and systolic/diastolic function secondary to chronic volume overload induced by an infrarenal arteriovenous (A-V) fistula in rats have not been well characterized. To this end, LV end-diastolic pressure, size, and function (i.e., isovolumetric pressure-volume relationships in the blood-perfused isolated heart) were assessed at 1, 2, 3, 5, and 8 wk post-A-V fistula and compared with age-matched control animals. Progressive hypertrophy (192% at 8 wk), ventricular dilatation (172% at 8 wk), and a decrease in ventricular stiffness (257% at 8 wk) occurred in the fistula groups. LV end-diastolic pressure increased from a control value of 4.2 +/- 3.1 mmHg to a peak value of 15.7 +/- 3.6 mmHg after 3 wk of volume overload. A subsequent decline in LVEDP to 11.0 +/- 6.0 mmHg together with further LV dilation (169%) corresponded to a significant decrease in LV stiffness (222%) at 5 wk post-A-V fistula. Myocardial contractility, as assessed by the isovolumetric pressure-volume relationship, was significantly reduced in all A-V fistula groups; however, the compensatory remodeling induced by 8 wk of chronic biventricular volume overload tended to preserve systolic function.


2010 ◽  
Vol 298 (2) ◽  
pp. H497-H504 ◽  
Author(s):  
Jason D. Gardner ◽  
David B. Murray ◽  
Tetyana G. Voloshenyuk ◽  
Gregory L. Brower ◽  
Jessica M. Bradley ◽  
...  

We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload.


2004 ◽  
Vol 287 (5) ◽  
pp. H1994-H2002 ◽  
Author(s):  
Hiroshi Ashikaga ◽  
Jeffrey H. Omens ◽  
James W. Covell

To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 ± 2 wk (means ± SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 ± 0.030; P < 0.05), whereas the apical site did not [ P = not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 ± 0.003 at 2 wk and 0.054 ± 0.021 at final; both P < 0.05), which contributed to a significant increase in wall thickness at the final study (0.181 ± 0.047; P < 0.05), whereas the apical site did not ( P = NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.


Hypertension ◽  
2006 ◽  
Vol 47 (1) ◽  
pp. 128-133 ◽  
Author(s):  
Emmanuelle Souzeau ◽  
Bastien Llamas ◽  
Sonia Bélanger ◽  
Sylvie Picard ◽  
Christian F. Deschepper

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Amr Abdel Aal ◽  
Housam M. Hassan ◽  
Dina Ezzeldin ◽  
Maiy El Sayed

Abstract Background Ventricular septal defect (VSD) is the most common congenital heart disease. In patients with large VSD, left side chambers are subjected to volume overload with subsequent chambers dilatation and eccentric left ventricular hypertrophy. Percutaneous closure of VSD has been shown to be an effective method with equal safety and efficacy when compared to surgery. The effect of VSD closure on LV remodeling has been mainly assessed in patients treated with surgery and to date published data remain scarce. Therefore, we aim to evaluate the effect of percutaneous VSD closure on different LV parameters. Results Seventeen patients (median age 6 years (IQR 4.75–8 years), 70.6% females) who underwent percutaneous VSD closure were enrolled in the study. Sixteen patients (94%) had perimembranous VSD, and one patient had muscular VSD. The procedure was successful in all patients with no major complications. Nit Occlud® Lê coil device was implanted in 16 patients (94%), and one patient received Amplatzer PDA duct occlude device. At 6-months follow-up, there was a significant reduction in indexed LV dimensions [LVEDD/BSA (median 46.5 mm/m2 vs. 42.9 mm/m2, p = 0.03), LVESD/BSA (median 31.7 mm/m2 vs. 26.7 mm/m2, p = 0.02)], indexed LV volumes [LVEDV/BSA (median 52.6 ml/m2 vs. 37.3 ml/m2, p = 0.02), LVESV/BSA (median 31.7 ml/m2 vs. 23.3 ml/m2, p = 0.02)] and indexed LV mass (median 62.4 gm/m2 vs. 57.9 ml/m2, p = 0.01). There was a significant reduction in LVEDD Z-score (p = 0.01) and LVESD Z-score (p = 0.04). There was no significant change in LV EF. Conclusions Percutaneous VSD closure is associated with improvement of various LV parameters with consequential favorable LV remodeling and function.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Zhang ◽  
Y.K Guo ◽  
Z.G Yang ◽  
M.X Yang ◽  
K.Y Diao ◽  
...  

Abstract Background Cardiac magnet resonance (CMR) T1 mapping allows the quantitative characterization of the severity of tissue injury and predict functional recovery in acute myocardial infarction (AMI). Purpose The study aimed to investigate whether native T1 and ECV of infarct myocardium are influenced by microvascular obstruction (MVO) and have predictive value for adverse left ventricular (LV) remodeling post-infarction. Method A cohort of 54 patients with successfully reperfused STEMI underwent CMR imaging at a 3T scanner in AMI and 3 months post-infarction. Native T1 data was acquired using a modified Look-Locker inversion recovery (MOLLI) sequence, and ECV maps were calculated using blood sampled hematocrit. Manual regions-of-interest were drawn within the infarct myocardium to measure native T1 and ECV (native T1infarct and ECVinfarct, respectively). MVO identified as a low-intensity area within the infarct zone on LGE was eliminated. Results MVO was present in 36 patients (66.67%) in AMI. ECVinfarct in patients with MVO was different from those without (58.66±8.71% vs. 49.64±8.82%, P=0.001), while no significant difference in T1infarct was observed between patients with and without MVO (1474.7±63.5ms vs. 1495.4±98.0ms, P=0.352). ECV correlated well with the change in end-diastolic volume (all patients: r=0.564, P&lt;0.001) and predicted LV remodeling in patients with and without MVO (rMVO absent = 0.626, P=0.005; rMVO present = 0.686, P&lt;0.001; all patients: r=0.622, P&lt;0.001); Native T1 was only associated with a 3-month change in LV end-diastolic volume (rMVO absent= 0.483, P=0.042) and predicted LV remodeling in patients without MVO (rMVO absent = 0.659, P=0.003). Furthermore, ECV had an association with LV remodeling (β=0.312, P=0.007) in multivariable logistic analysis. Conclusion Absolute native T1 in infarct myocardium might be affected by MVO but ECV isn't. ECV could predict LV remodeling in MI patients with and without MVO, while native T1 predict it in MI with MVO absent. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University


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