Abstract P411: Sex-based Differences In A Feline Model Of Hfpef

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Deborah M Eaton ◽  
Remus Berretta ◽  
Jacqueline E Lynch ◽  
Joshua G Travers ◽  
Kathleen C Woulfe ◽  
...  

Rationale: Heart Failure with preserved Ejection Fraction (HFpEF) accounts for approximately 50% of all HF diagnoses with no FDA approved therapies. HFpEF is more prevalent in females versus males, but the mechanisms driving the development of HFpEF as a sex-based disorder are not well understood. We have recently shown that slow progressive pressure overload (PO) in male felines induces a HFpEF phenotype but have not investigated the differences in response to the same physiological stress in females. Hypothesis: Females will develop a phenotype that is distinct from males in response to PO. Methods and Results: Male (m) and female (f) domestic short felines (age 2mo) underwent either a sham procedure (m: n=7; f: n=7) or aortic constriction (m: n=11; f: n=10) using a customized pre-shaped band. At baseline (prior to surgery), there was no difference in body weight between groups and echocardiography revealed no significant difference in the ratio of left atrium to aortic root (LA/Ao), LA ejection fraction (LA EF), left ventricle (LV) ejection fraction, LV wall-thickness, and E/A ratio. At 4mo post-surgery, both males and females developed cardiac dysfunction. Females gained significantly less weight than males throughout the study. Despite the size difference, both sexes developed comparable LV wall thickness and changes in E/A ratio vs. sham groups. There was no change in LV EF. Furthermore, there was a decrease in LA EF and increased LA/Ao, indicating LA dysfunction and enlargement. Invasive hemodynamics at 4mo post-surgery showed no differences between sexes for the systolic pressure gradient generated by the aortic banding. Banded males had a significantly higher LV end-diastolic pressure vs. banded females, but there was a trend towards prolongation of tau and lower dp/dt min in banded females, reflective of worse active relaxation. Both sexes had comparable dP/dt max . There were no differences between banded males and females in heart weight to body weight or cardiomyocyte cross-sectional area. Conclusion: Despite similar pressure gradients as a result of PO and the development of similar cardiac hypertrophy between sexes and a higher LVEDP in males, females had a trend towards worse relaxation. Other causes of HFpEF may have sex-based differences.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Joshua Oakes ◽  
Susan Hamilton

FK506 Binding Proteins (FKBPs) are a family of cis-trans prolyl isomerases that bind rapamycin and FK506. FKBP12 and 12.6 interact with ryanodine receptors (RyR), homotetrameric transmembrane ion channels that regulate Ca2+ release from the sarcoplasmic reticulum (SR). FKBP12 interacts with RyR1 in skeletal muscle and FKBP12.6 interacts with RyR2 in cardiac muscle to regulate the Ca2+ leak properties of these channels. Recently it has been suggested that FKBP12 also plays a role in regulating RyR2 activity. Using mice with a cardiac specific deficiency in FKBP12, we analyzed the role of FKBP12 in cardiac function. We found that both male and female mice with a α-MyHC Cre/Lox mediated deficiency in FKBP12 in the heart (FKBP12 KD) developed a mild dilated cardiomyopathy, with enlarged left ventricular diameter both during systole and diastole, decreased ejection fraction and decreased fractional shortening. To elucidate the mechanism for these effects we assessed Ca2+ sparks in isolated cardiomyocytes. We found an increase in both Ca2+ spark frequency and spark amplitude in FKBP12 cardiac deficient mice without a change in spark duration. Despite a mild phenotype in adult mice, we found that approximately 25% of all pregnancies (26/106) in the FKBP12 deficient mice resulted in the mothers dying following the birth. Autopsies show that these cardiac specific FKBP12 deficient mice had increased heart weight and significantly dilated ventricles compared to female Cre mice. Our data suggest that a cardiac specific deficiency in FKBP12 leads to the development of pregnancy induced cardiomyopathy. Echocardiography on FKBP12 deficient mice one day after giving birth found that there was no significant difference in ejection fraction or fractional shortening compared to α-MyHC Cre control mice. FKBP12 deficient females, however, had larger hearts and 50% (2/4) displayed heart failure and died. In conclusion, we show that FKBP12 does indeed alter Ca2+ handling in the heart and that a loss of FKBP12 leads to the development of pregnancy induced cardiomyopathies in females.


2009 ◽  
Vol 24 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Honório Sampaio Menezes ◽  
Cláudio Galeano Zettler ◽  
Alice Calone ◽  
Jackson Borges Corrêa ◽  
Carla Bartuscheck ◽  
...  

PURPOSE: To compare body weight and length, heart weight and length, heart-to-body weight ratio, glycemia, and morphometric cellular data of offspring of diabetic rats (ODR) and of normal rats (control). METHODS: Diabetes was induced in 3 pregnant Wistar rats, bearing 30 rats, on the 11th day after conception by intraperitoneal injection of 50 mg/kg of streptozotocin. Six normal pregnant Wistar rats, bearing 50 rats, made up the control group. Morphometric data were obtained using a scale for the weight, length, heart and body measurements. Morphometric cellular data were obtained by a computer assisted method applied to the measurements of myocytes. Statistical analysis utilized Student's t-test, ANOVA and Levene test. RESULTS: Control offspring had greater mean body weight and length than offspring of diabetic rats (p < 0.001). Heart weight and length and heart-to-body ratios of newborn rats differed between groups at birth (p < 0.001), but showed no difference at 21 days. Mean nuclei area and perimetric value of the myocytes decrees throughout the first 21 days of life (p < 0.01) in the diabetic group. CONCLUSIONS: Heart hypertrophy on the offspring of diabetic rats at birth was demonstrated by the significant difference between the groups. After the eleventh day, no difference was found, which confirmed regression of cardiomegaly. The significant difference between the first and the 21th day of life, for nuclei area feature, demonstrate regression of cardiac hypertrophy in the offspring of diabetic rats.


PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Si-Yu Zeng ◽  
Hui-Qin Lu ◽  
Qiu-Jiang Yan ◽  
Jian Zou

The peroxisome proliferator-activated receptor-α (PPAR-α) agonist fenofibrate ameliorates cardiac hypertrophy; however, its mechanism of action has not been completely determined. Our previous study indicated that a disintegrin and metalloproteinase-17 (ADAM17) is required for angiotensin II-induced cardiac hypertrophy. This study aimed to determine whether ADAM17 is involved in the protective action of fenofibrate against cardiac hypertrophy. Abdominal artery constriction- (AAC-) induced hypertensive rats were used to observe the effects of fenofibrate on cardiac hypertrophy and ADAM17 expression. Primary cardiomyocytes were pretreated with fenofibrate (10 μM) for 1 hour before being stimulated with angiotensin II (100 nM) for another 24 hours. Fenofibrate reduced the ratios of left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW), left ventricular anterior wall thickness (LVAW), left ventricular posterior wall thickness (LVPW), and ADAM17 mRNA and protein levels in left ventricle in AAC-induced hypertensive rats. Similarly, in vitro experiments showed that fenofibrate significantly attenuated angiotensin II-induced cardiac hypertrophy and diminished ADAM17 mRNA and protein levels in primary cardiomyocytes stimulated with angiotensin II. In summary, a reduction in ADAM17 expression is associated with the protective action of PPAR-α agonists against pressure overload-induced cardiac hypertrophy.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J W Seo ◽  
K U Choi ◽  
J Y Choi ◽  
P J Lkhagvasuren ◽  
C Y Shim ◽  
...  

Abstract Background A few studies have demonstrated bi-ventricular hypertrophy in hypertrophic cardiomyopathy (HCM). However, clinical significance of HCM with right ventricular (RV) involvement has not been fully established. Therefore, we aimed to investigate the structural characteristics and clinical significance of RV hypertrophy in patients with HCM. Methods In a single center, large HCM registry, 256 patients with HCM who underwent both cardiac magnetic resonance (CMR) and transthoracic echocardiography within 6 months were retrospectively analyzed. RV involvement was defined as increased RV wall thickness >7 mm on CMR in any segments of RV free wall and apex. Patients who had evidence of significant RV pressure overload (RV systolic pressure >50mmHg) or had undergone septal myectomy were excluded. Cardiovascular outcomes were defined as the composite of cardiovascular death and hospitalization for cardiovascular disease. Results Among 256 patients, 41 (16%) showed RV involvement. During follow-up period (median 1099 days), 32 cardiovascular outcomes (3 cardiovascular death and 29 cardiovascular hospitalization) were occurred. Patients with RV involvement showed a significantly higher left ventricular (LV) thickness (23.8±5.8 vs. 21.2±5.0 mm, p=0.004), more advanced diastolic dysfunction, and larger left atrial volume index (LAVI, 48.5±20.3 vs. 40.2±14.9 mm/m2, p=0.016) compared to those without RV involvement. In multivariate cox regression analysis, presence of RV involvement (HR: 4.21, 95% CI: 1.99–8.90, p<0.001) and LV ejection fraction <50% (HR: 4.29, 95% CI: 1.37–13.43, p=0.012) were independently associated with cardiovascular outcomes. The Kapan-Meier curve showed that there was a significant decrease in probability of cardiovascular outcomes-free survival in patients with RV involvement (p=0.007) after using 1:1 propensity score matching (n=82) to adjust for age, sex, LV ejection fraction, LV maximal wall thickness, LAVI, and RV systolic pressure than patients without RV involvement (Figure 1). Figure 1 Conclusion RV involvement in patients with HCM were not rare (16%). Patients with RV involvement showed more advanced LV structure and dysfunction, suggesting an indicator of severe HCM. RV involvement in HCM has clinical significance related to cardiovascular outcomes.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A I H Phua ◽  
S W Tara ◽  
T T Le ◽  
J A Bryant ◽  
D F K Toh ◽  
...  

Abstract Funding Acknowledgements National Medical Research Council OnBehalf National Heart Centre Singapore BACKGROUND Adverse cardiac remodelling is associated with worse cardiovascular outcomes. Development of left ventricular hypertrophy (defined as increased myocardial mass) is a complex process mediated by myocardial wall thickening and/or ventricular dilatation. Sex-related differences in the relationship between myocardial mass and wall thickening/ventricular dilatation have not been well-described. PURPOSE We examine differences in determinants and patterns of cardiac remodeling between males and females. METHODS Comprehensive cardiovascular magnetic resonance imaging was performed in 1006 participants: 316 healthy volunteers (50% males, 46 ± 14 years) and 690 asymptomatic hypertensive patients (60% males, 57 ± 11 years). Myocardial mass, ventricular volumes and maximal myocardial wall thickness (across 16 myocardial segments) were measured using standardized contouring techniques. Clinically relevant variables (age, weight, height, and adiposity) that demonstrated significant univariate association with myocardial mass (P &lt; 0.05) were selected in the multivariable linear regression model using the forward approach. RESULTS Increased body weight, lower body fat composition and higher systolic blood pressures were independently associated with increased myocardial mass in healthy volunteers (males and females) and hypertensive females. In hypertensive males, only increased body weight and elevated systolic blood pressure were independently associated with increased myocardial mass. The association between myocardial mass and ventricular volumes was almost identical between males and females (P = 0.65 for interaction; Figure). Conversely, there was a significant gender-related difference in the association between wall thickness and myocardial mass after adjusting for potential confounders (P &lt; 0.001 for interaction). Concentric remodeling was initially more evident in males; but further with increase, myocardial mass was associated with greater concentric remodeling in females (Figure). Similar results were observed when analyses were performed separately in healthy volunteers and hypertensive patients. CONCLUSION There were sex-related differences in concentric remodeling at progressive stages of myocardial hypertrophy that may explain the higher prevalence of heart failure with preserved ejection fraction reported in females. Abstract P1419 Figure


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Fathimath Naseer ◽  
Ruth Price ◽  
Adele McElroy ◽  
Carel Le Roux ◽  
Tamsyn Redpath ◽  
...  

AbstractBariatric surgery, including Gastric Bypass (GBP) Surgery, is the most efficient modality to manage severe obesity. Resting Energy Expenditure (REE) is an area of interest in the context of weight loss (WL) as it has been postulated to be an independent predictor of WL success following GBP. As such, the aim of this study is to investigate the impact of REE on WL following GBP. 31 GBP patients (77.4% females BMI 45.5 ± 7.0kg/m2 ; 47.3 ± 11.6y) and 32 weight-stable controls (46.9% females; BMI 27.0 ± 4.6kg/m2 ; 41.1 ± 13.5y) were assessed at one-month pre-surgery and at 3 and 12-months post-surgery. Fat mass (FM) and fat-free mass (FFM) were measured using dual energy X-ray absorptiometry (Lunar iDXA, GE Healthcare). REE was measured under standardised conditions using indirect calorimetry (ECAL, Metabolic Health Solutions). Statistical analyses were performed with SPSS v24.0, Armonk, NY. Multiple regression analysis showed that FM (P = 0.001), FFM (P < 0.0001) and gender (P = 0.012) significantly predicted the interindividual variability in REE. Total body weight (TBW) was removed from the model due to collinearity. Adjusted-REE values were then generated using the above predictor variables. Low-REE and high-REE groups were created using within-group adjusted-REE split. At both follow-ups (3- and 12-months post-surgery), patients had a greater reduction in TBW, FM, FFM, measured-REE and adjusted-REE values compared with controls (P < 0.0001). There was also no significant difference between measured and adjusted-REE values at all time-points (P > 0.05). Patients with high REEs at baseline lost more TBW than those in the low-REE group at 3-months post-surgery (-24.9 ± 6.5 kg vs. -16.6 ± 7.0 kg; P = 0.005) and 12-months post-surgery (-41.3 ± 12.5 kg vs. -25.8 ± 10.4.0 kg; P = 0.003). There was no significant difference in mean TBW changes for controls in the low-and high-REE groups at both follow-ups. Patients with high REEs at 3-months post-surgery did not lose more TBW than those in the low-REE group at 12-months post-surgery (-30.1 ± 12.8 kg vs. -38.6 ± 14.4 kg; P = 0.155). Similarly, there was no difference in mean TBW reduction between controls in the low- and high-REE groups (P = 0.115). Thus while patients with a high adjusted-REE value at baseline (> 9746.6kJ/day) lost more weight at 3- and 12-months post-GBP, it is plausible that from the third to the 12th month post-surgery, other key drivers of weight loss, particularly the reduction in energy intake are more important in predicting WL. Further research with a larger sample size is required to increase the chances of detecting a true effect.


1987 ◽  
Vol 252 (4) ◽  
pp. H788-H795 ◽  
Author(s):  
K. H. McDonough ◽  
V. Chen ◽  
J. J. Spitzer

Effect of a chronic excess or deficit of thyroid hormone on intrinsic myocardial performance in rats was assessed. Animals were thyroidectomized or treated with thyroid hormone or vehicle 6-7 wk before the study. Body weight and heart weight were decreased in the hypothyroid group, and heart weight was elevated in the hyperthyroid group. Hearts were removed from thyroidectomized, euthyroid or thyroid-treated animals and studied as isolated, perfused working heart preparations. Ventricular function curves were generated by increasing left atrial filling pressure, whereas outflow resistance was not varied. Coronary flow, aortic outflow (and thus cardiac output), heart rate, and peak aortic systolic pressure were measured as a function of preload. These studies showed that performance of hearts from hyperthyroid animals was similar to that of euthyroid controls. Hearts from hypothyroid rats had decreased rate, pressure, and cardiac output but normal stroke volume. Since heart weight was 55% lower than control, normalization of volume work to dry heart weight reversed the difference in cardiac output. Comparison of hearts from hypothyroid animals to control rats of similar weight showed minimal differences in pump function. Thus hyperthyroidism did not result in altered in vitro cardiac output or peak systolic pressure as a function of changing preload when compared with age-matched euthyroid controls, hypothyroidism resulted in a decreased in vitro heart rate but greater cardiac output normalized to heart weight when compared with age-matched controls and hyperthyroid animals; external pacing of hypothyroid hearts yielded myocardial work parameters that were comparable to euthyroid control rats of similar body weight; and cardiac efficiency was significantly greater in hypothyroid hearts than in hyperthyroid hearts.(ABSTRACT TRUNCATED AT 250 WORDS)


2021 ◽  
Vol 7 (2) ◽  
pp. 62-68
Author(s):  
Andreas Arie Setiawan ◽  
Fairuz Azmila Purnomo ◽  
Vega Karlowee ◽  
Noor Wijayahadi

ABSTRACTBackground: Obesity is a disorder or disease characterized by the accumulation of excess fat in the body due to an imbalance in energy intake that is used for a long time. Accumulation of fat can reduce adiponectin, causing cardiac hypertrophy, endothelial vasodilation, and other cardiovascular diseases. Black garlic have high antioxidants in the form of S-Allylcysteine(SAC) which functions to increase adiponectin. Objective: To determine the effect of Black garlic on the histopathological picture of the heart and aorta of obese rats. Methods: This study was an experimental study with a randomized post-test only design with control group design with 5 groups of male white rats Sprague Dawley (Rattus novergicus) fed High Fat Fructose. Diet (HFFD) enriched with 1.25% cholesterol and 0.5% cholic acid for 8 weeks and was given black garlic intervention at doses of 450 mg / 200BW, 900mg / 200BW and 1350mg200 / BW for 4 weeks. Results: Giving black garlic significantly reduced body weight of rats (p = 0.001), and the results did not significantly reduce heart weight (p = 0.147), aortic weight (p = 0.061), histopathological changes in heart wall thickness (p = 0.423) and aortic wall thickness (p = 0.802). The effective doses of black garlic in this study were 450 mg / 200 grams BW, 900 mg / 200 grams rat BW and 1350 mg / 200 grams BW of rats. The optimal dose is 900 mg / 200 grams BW. Conclusion: Black garlic gave a significant reduction in body weight of rats and no significant reduction in heart weight, aortic weight, cardiac and aortic histopathological features. 


2020 ◽  
Vol 33 (1) ◽  
pp. 50-55
Author(s):  
Andressa Moreira ◽  
Alessandra Nicolini ◽  
Eduardo Gaio ◽  
Fernanda Visioli ◽  
Cassiano Rösing ◽  
...  

The purpose of this study was to evaluate aortic wall thickness after periodontal disease and/or obesity induction in a Wistar rat model.Sixty male Wistar rats were randomly divided into four groups: control (CT), periodontal disease (PD), obesity (OB), and obesity plus periodontal disease (OB+PD). Groups OB and OB+PD received cafeteria diet for 17 weeks. After they had acquired obesity (week 12), periodontal disease was induced by placing a silk ligature on the maxillary right second molar of groups PD and OB+PD. During the experimental period, body weight and Lee index were assessed. Mean alveolar bone loss (ABL) was evaluated, and aortas were prepared for histometric analysis of the aortic wall by ImageJ software. Body weight and Lee index increased in rats exposed to cafeteria diet. Mean ABL was higher in Groups PD and OB+PD than in control and OB (p<0.05). ABL was 18% higher in Group OB+PD than in Group PD, with statistically significant difference (p<0.001). Aortas were thicker in Groups OB and OB+PD than in control and PD groups, respectively (2.31mm ± 0.28 and 2.33 ± 0.29 vs. 2.18 ± 0.26 and 2.14 ± 0.27). Group OB differed significantly from the control group (p=0.036), and OB+PD and OB differed significantly from PD (p=0.004 and p= 0.001, respectively). Obesity alters aortic wall thickness in Wistar rats. However, the presence of periodontal disease did not affect the aortic wall thickness under the conditions of the present study.


1962 ◽  
Vol 40 (1) ◽  
pp. 151-160 ◽  
Author(s):  
D. W. Snair

ABSTRACT The assay of corticotrophin in weanling rats, using the decrease in thymus weight as a criterion of response is described. A straight line was obtained over the range of doses of 120–1920 milliunits* when the log dose was plotted against the thymus weight per 100 g of body weight. A study of the factors affecting the assay has shown that there is no significant difference in response between males and females and that the thymus weight bears a direct relation to body weight over the range used. Multiple injections increased the sensitivity of the animals to corticotrophin but did not affect the precision of the assay. Purified corticotrophin preparations were found to have the same relative potency by the thymus involution method as by other subcutaneous injection assay methods.


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