scholarly journals Cardiac hypertrophy with obesity is augmented after pregnancy in C57BL/6 mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Chen Che ◽  
Kayla Dudick ◽  
Robin Shoemaker
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Premenopausal Women ◽  
Left Ventricular ◽  
Mrna Abundance ◽  
Reproductive Age ◽  
Altered Expression ◽  
Lv Mass ◽  
Plasma Leptin

Abstract Background Over a third of reproductive-age women in the USA are obese, and the prevalence of cardiovascular disease (CVD) is rising in premenopausal women. Cardiac hypertrophy is an independent predictor of CVD. In contrast to pregnancy, where transiently increased left ventricular (LV) mass is not associated with cardiac damage, obesity-mediated cardiac hypertrophy is pathological. There is a paucity of data describing the effect of obesity during pregnancy on maternal cardiovascular health. The purpose of this study was to determine the long-term effect of obesity during pregnancy on cardiac function and structure in mice. Methods Female C57BL/6 J mice were fed a high-fat (HF) or a low-fat (LF) diet for 20 weeks. After 4 weeks, LF- and HF-fed female mice were either crossed with males to become pregnant or remained non-pregnant controls. Following delivery, pups were euthanized, and females maintained on respective diets. After 20 weeks of diet feeding, cardiac function was quantified by echocardiography, and plasma leptin and adiponectin concentrations quantified in LF- and HF-fed postpartum and nulliparous females. mRNA abundance of genes regulating cardiac hypertrophy and remodeling was quantified from left ventricles using the NanoString nCounter Analysis System. Cardiac fibrosis was assessed from picrosirius red staining of left ventricles. Results HF-fed postpartum mice had markedly greater weight gain and fat mass expansion with obesity, associated with significantly increased LV mass, cardiac output, and stroke volume compared with HF-fed nulliparous mice. Plasma leptin, but not adiponectin, concentrations were correlated with LV mass in HF-fed females. HF feeding increased LV posterior wall thickness; however, LV chamber diameter was only increased in HF-fed postpartum females. Despite the marked increase in LV mass in HF-fed postpartum mice, mRNA abundance of genes regulating fibrosis and interstitial collagen content was similar between HF-fed nulliparous and postpartum mice. In contrast, only HF-fed postpartum mice exhibited altered expression of genes regulating the extracellular matrix. Conclusions These results suggest that the combined effects of pregnancy and obesity augment cardiac hypertrophy and promote remodeling. The rising prevalence of CVD in premenopausal women may be attributed to an increased prevalence of women entering pregnancy with an overweight or obese BMI.

Abstract 314: BRaf Plays a Major Role in Gene Expression in Cardiomyocytes in Mouse Hearts in vivo

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Michelle A Hardyman ◽  
Stephen J Fuller ◽  
Daniel N Meijles ◽  
Kerry A Rostron ◽  
Sam J Leonard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Braf Mutations ◽  
Gene Markers ◽  
Lv Mass ◽  
Cardiac Volumes

Introduction: Raf kinases lie upstream of ERK1/2 with BRaf being the most highly expressed and having the highest basal activity. V600E BRaf mutations constitutively activate ERK1/2 and are common in cancer. The role of BRaf in the adult heart is yet to be established. ERK1/2 regulate cardiomyocyte gene expression, promoting cardiac hypertrophy and cardioprotection, but effects of ERK1/2 may depend on signal strength. Hypothesis: Our hypotheses are that BRaf is critical in regulating ERK1/2 signaling in cardiomyocytes and, whilst moderate ERK1/2 activity is beneficial, excessive ERK1/2 activity is detrimental to the heart. Methods: We generated heterozygote mice for tamoxifen- (Tam-) inducible cardiomyocyte-specific knockin of V600E in the endogenous BRaf gene. Mice (12 wks) received 2 injections of Tam or vehicle on consecutive days (n=4-10 per group). Kinase activities and mRNA expression were assessed by immunoblotting and qPCR. Echocardiography was performed (Vevo2100). M-mode images (short axis view) were analyzed; data for each mouse were normalized to the mean of 2 baseline controls. Results: V600E knockin did not affect overall BRaf or cRaf levels in mouse hearts, but significantly increased ERK1/2 activities within 48 h (1.51±0.05 fold). Concurrently, mRNAs for hypertrophic gene markers including BNP and immediate early genes (IEGs) increased signficantly. At 72 h, expression of BNP, Fosl1, Myc, Ereg and CTGF increased further, other IEGs (Jun, Fos, Egr1, Atf3) declined, and ANF was upregulated. In contrast, expression of α and β myosin heavy chain mRNAs was substantially downregulated (0.46/0.41±0.05 relative to controls). Within 72 h, left ventricular (LV) mass and diastolic LV wall thickness had increased (1.23±0.05 relative to controls), but cardiac function was severely compromised with significant decreases in ejection fraction and cardiac output (0.53/0.68±0.09 relative to controls) associated with increased LV internal diameters and cardiac volumes. Conclusions: Endogenous cardiomyocyte BRaf is sufficient to activate ERK1/2 in mouse hearts and induce cardiac hypertrophy associated with dynamic temporal changes in gene expression. However, excessive activation of ERK1/2 in isolation is detrimental to cardiac function.

Abstract 13810: TT-00920, a Clinical Stage Novel Phosphodiesterase 9 Inhibitor, Protects Against Heart Failure in a Rat Model of Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Zejuan Sheng ◽  
Xiaoyan Qiang ◽  
Guoyu Li ◽  
Huimin Wang ◽  
Wenxin Dong ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Rat Model ◽  
Cardiac Fibrosis ◽  
Clinical Stage ◽  
Left Ventricular ◽  
Guanosine Monophosphate ◽  
Therapeutic Effects ◽  
Dependent Manner

Introduction: Phosphodiesterase 9 (PDE9) controls natriuretic-peptide-stimulated cyclic guanosine monophosphate in cardiac myocytes and is stongly upregulated in human heart failure, suggesting its potential as a promising therapeutic target in heart failure. Here we investigated the potential effects of TT-00920, a clinical stage novel and highly selective PDE9 inhibitor, on heart failure in a rat model of myocardial infarction. Methods: Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation in male Sprague Dawley rats. After 4-week treatment of vehicle, LCZ696, TT-00920, or TT-00920/Valsartan by oral gavage, efficacy was assessed by echocardiography and cardiac histopathology. Results: TT-00920 had remarkably improved cardiac function, protected against cardiac remodeling and fibrosis in a dose-dependent manner. TT-00920/Valsartan combination showed superior beneficial efficacy when compared to TT-00920 or LCZ696 single agent.Figure 1. TT-00920 improved cardiac function and ventricular remodeling.Figure 2. TT-00920 attenuated cardiac fibrosis in peri-infarct zone. Conclusions: TT-00920 reversed LAD-induced left ventricular dysfunction and remodeling, supporting its potential as a novel therapeutic agent for heart failure. The superior efficacy of TT-00920/Valsartan combination suggests that TT-00920 and renin-angiotensin-aldosterone system inhibitors may have additive therapeutic effects in heart failure.TT-00920 is currently being evaluated in Phase 1 clinical study for safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers (NCT04364789).

Abstract 61: Ablation of BK Ca Channels Results in Cardiac Hypertrophy

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Harpreet Singh ◽  
Kajol Shah ◽  
Devsena Ponnalagu ◽  
Sanjay Chandrasekhar ◽  
Andrew R Kohut ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Structural Changes ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Interventricular Septum ◽  
Wild Type

Expression and activation of the large conductance calcium and voltage-gated potassium (BK Ca ) channels encoded by Kcnma1 gene is shown to be vital in cardioprotection from ischemia-reperfusion injury. BK Ca channels present in SA node cells regulate the heart rate, and in blood vessels play an active role in vascular relaxation. However, the role of BK Ca in regulation of structure and function of the heart is not fully-established. Using Kcnma1 -/- mice, we have observed structural changes in cardiomyocytes and compromised cardiac function as compared to wild type mice. Absence of BK Ca resulted in significant increase in size of adult cardiomyocytes (from 7.95 + 0.1 um 2 to 9.68 + 0.1 um 2 , p < 0.01, n=480 cells each) and also increased cardiac fibrosis. Further to determine underlying signaling mechanisms in cardiac hypertrophy, we performed microarray analysis of RNAs isolated from wild type and Kcnma1 -/- mice (n=3) hearts. We found up regulation of a class of cardiac hypertrophy markers (myosin variants) and changes in the expression of several mitochondrial genes (such as ND4) directly associated with heart diseases in Kcnma1 -/- mice. To evaluate the functional consequence of absence of BK Ca , we performed high-resolution echocardiography on wild type and Kcnma1 -/- mice. Under anesthesia (1.5% isoflurane), left ventricle of Kcnma1 -/- mice showed significant reduction (p < 0.05) in ejection fraction (56 + 2 %, n=7) as compared to wild type (74 + 3 %, n=6) as well as fractional shortening (23 + 3 %, n=7, and 39 + 3 %, n=6, respectively). Similarly, right ventricle had a lower ejection fraction (35.7 + 4% vs 56.9 + 5 %, n > 5) in Kcnma1 -/- as compared to wild type mice. In agreement with our histopathology and microarray data, Kcnma1 -/- mice showed increased posterior wall thickness (0.75 + 0.3 mm vs 0.62 + 0.1 mm) and interventricular septum thickness (0.83 + 0.4 mm, n=7 vs 0.68 + 0.3 mm, n=6) . Together, these data imply that BK Ca plays a direct role in cardiac hypertrophy and cardiac function.

Abstract P372: Trajectories in Fasting Glucose and Insulin Resistance During Young Adulthood and Measures of Cardiac Function and Structure in Middle Adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Michael P Bancks ◽  
Mercedes Carnethon ◽  
Lisa S Chow ◽  
David R Jacobs ◽  
Satoru Kishi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiac Function ◽  
Young Adulthood ◽  
Left Atrial ◽  
Fasting Glucose ◽  
Left Ventricular ◽  
Middle Adulthood ◽  
End Diastolic Volume ◽  
Lv Mass ◽  
Stable Trajectory

Introduction: Whether trajectories in fasting glucose (FG) and insulin resistance (HOMA-IR) during young adulthood, before the onset of diabetes, are associated with cardiac function and structure in middle adulthood is unclear. Hypothesis: We tested the hypothesis that as compared to low-stable trajectory of FG and HOMA-IR, an increasing trajectory for each would be associated with worse cardiac structure and function in middle adulthood. Methods: We determined FG and HOMA-IR for 2,198 CARDIA participants, age 18-30 years, at baseline (1985-1986) and 7, 10, 15, 20, and 25 year follow-up exams who fasted for >8 hours and were not pregnant and were free from diabetes at all exams. At year 30 (2016), Doppler echocardiography and 2D-guided M-mode echocardiography was performed, measuring left atrial dimension, relative wall thickness, left ventricular (LV) mass, LV mass indexed to height, LV ejection fraction percentage, LV end-diastolic and systolic volume, and LV mass to volume ratio. Trajectories were determined using latent class analysis (SAS Proc Traj). We used multivariable linear regression to estimate adjusted means for echo measures according to FG and HOMA-IR trajectory group after adjustment for potential confounding factors. Results: For individuals free from diabetes in midlife, we identified three trajectory groups for both FG and HOMA-IR, low-stable to increasing, moderate-increasing, and high-increasing. Compared to low-stable trajectory for FG, increasing trajectory was associated with greater LV end-diastolic volume, whereas for HOMA-IR increasing trajectory was associated with lower LV end-diastolic volume ( Table ). Increasing FG trajectory was also associated with greater left atrial dimension, while HOMA-IR was not. Conclusion: Trajectory of both FG and HOMA-IR during young adulthood, in the absence of diabetes, was most prominently and differentially associated with LV end-diastolic volume. Future research should elaborate on differential associations of FG and HOMA-IR trajectory.

scholarly journals P0254MYOCARDIAL TISSUE CHARACTERIZATION IN LIVING KIDNEY DONORS 5 YEARS AFTER NEPHRECTOMY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Price ◽  
Victoria Stoll ◽  
Ravi Vijapurapu ◽  
Kirsty McGee ◽  
Roman Wesolowski ◽  
...  
Keyword(s):  
Late Gadolinium Enhancement ◽  
T1 Mapping ◽  
Cardiac Fibrosis ◽  
Left Ventricular ◽  
Healthy Controls ◽  
Gadolinium Enhancement ◽  
Post Contrast ◽  
Kidney Donors ◽  
Living Kidney Donors ◽  
Lv Mass

Abstract Background and Aims Uraemic cardiomyopathy is characterized by left ventricular (LV) hypertrophy, diastolic dysfunction and myocardial fibrosis. Diffuse interstitial fibrosis of the myocardium, assessed using cardiac magnetic resonance imaging (CMR) techniques of native T1-mapping and extracellular volume (ECV), has been demonstrated in end stage chronic kidney disease (CKD) and in patients with stage 3 CKD and normal left ventricular mass. In living kidney donors estimated glomerular filtration rate (eGFR) declines by a third after donation, with 60% having a resultant eGFR comparable with stage 3 CKD. Recent studies have demonstrated small increases in LV mass at 12 months after donation as well as functional sequelae of reduced global circumferential strain and apical torsion. We sought to establish whether living kidney donors had CMR evidence of diffuse interstitial cardiac fibrosis which might contribute to observed functional correlates. Method A cross sectional blinded study of living kidney donors (n=50) and healthy controls (n=45) who underwent 3 Tesla CMR and blood samples for biomarkers of fibrosis. A modified look-locker inversion recovery (MOLLI) 5(3)3 sampling scheme was used for T1 mapping followed by T2 mapping sequences at the mid LV slice. Five minutes after the administration of gadolinium (Gadovist®) contrast (0.15mmol/kg), standard T1-weighted gradient echo inversion recovery images were repeated for the assessment of late gadolinium enhancement (assessment for focal fibrosis). Post contrast MOLLI images were acquired using identical slice positions as native images using a 4(1)3(1)2 sampling scheme 15 minutes after the administration of gadolinium. Native and post contrast T1 time was used to calculate ECV. Results There were no differences in demographics between groups; age (donors 54 ± 12yrs vs. healthy controls 50 ± 13yrs, p=0.128), ethnicity (89% Caucasian) or male gender (37%). LV mass and volumes were not significantly different. Forty four donors and 34 controls consented to receive gadolinium contrast. Native T1 in the septal mid LV slice was not significantly different between groups (donors 1223 ± 35ms vs. controls 1210 ± 36ms, p=0.102). There was also no difference in T2 time of the septal mid LV slice (donors 40 ± 2ms vs. controls 40 ± 4ms vs. p=0.455). Late gadolinium enhancement was seen in five living kidney donors in a right ventricular insertion point pattern but there was no mid wall or ischaemic pattern enhancement. There was no difference in septal ECV at the mid LV slice (donors 25 ± 2% vs. controls 25 ± 2%, p=0.896). There was also no corresponding difference in fibroblast growth factor-23 (RU/ml) in donors 74 [58-105] vs. controls 59 [47-75], p=0.081 or soluble α-klotho (pg/ml) in donors 610 [503-810] vs. controls 703 [550-955], p=0.061. Conclusion Septal T1 times and ECV in living kidney donors at 5 years from donation are no different from healthy controls. Biomarkers of cardiac fibrosis are also comparable to healthy controls in this small cohort. We found no CMR evidence of the ultrastructural changes reported in uraemic cardiomyopathy in the hearts of living kidney donors at 5 years from donation.

A neutralizing leptin receptor antibody mitigates hypertrophy and hemodynamic dysfunction in the postinfarcted rat heart

2008 ◽  
Vol 295 (1) ◽  
pp. H441-H446 ◽  
Author(s):  
Daniel M. Purdham ◽  
Venkatesh Rajapurohitam ◽  
Asad Zeidan ◽  
Cathy Huang ◽  
Garrett J. Gross ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Leptin Receptor ◽  
Diastolic Pressure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Receptor Blockade ◽  
Receptor Antibody ◽  
Postinfarction Remodeling

The 16 kDa adipokine leptin has been shown to exert direct hypertrophic effects on cultured cardiomyocytes although its role as an endogenous contributor to postinfarction remodeling and heart failure has not been determined. We therefore investigated the effect of leptin receptor blockade in vivo on hemodynamic function and cardiac hypertrophy following coronary artery ligation (CAL). Cardiac function and biochemical parameters were measured in rats subjected to 7 or 28 days of left main CAL in the presence and absence of a leptin receptor antibody. Animals subjected to an identical treatment in which the artery was not tied served as sham-operated controls. CAL produced myocardial hypertrophy, which was most pronounced 28 days postinfarction as demonstrated by increases in both left ventricular weight-to-body weight ratio and atrial natriuretic peptide gene expression, both of which were abrogated by leptin receptor antagonism. Leptin receptor blockade also significantly improved left ventricular systolic function, attenuated the increased left ventricular end-diastolic pressure, and reduced the expression of genes associated with extracellular matrix remodeling 28 days following CAL. In conclusion, the ability of a leptin receptor-neutralizing antibody to improve cardiac function offers evidence that endogenous leptin contributes to cardiac hypertrophy following CAL. The possibility exists that targeting the myocardial leptin receptor represents a viable and novel approach toward attenuating postinfarction remodeling.

Developmental changes of cardiac function and mass assessed with MRI in neonatal, juvenile, and adult mice

2000 ◽  
Vol 278 (2) ◽  
pp. H652-H657 ◽  
Author(s):  
Frank Wiesmann ◽  
Jan Ruff ◽  
Karl-Heinz Hiller ◽  
Eberhard Rommel ◽  
Axel Haase ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Age Groups ◽  
Left Ventricular ◽  
Cine Mri ◽  
Transgenic Mouse Models ◽  
Adult Mice ◽  
Lv Mass

Cardiovascular transgenic mouse models with an early phenotype or even premature death require noninvasive imaging methods that allow for accurate visualization of cardiac morphology and function. Thus the purpose of our study was to assess the feasibility of magnetic resonance imaging (MRI) to characterize cardiac function and mass in newborn, juvenile, and adult mice. Forty-five C57bl/6 mice from seven age groups (3 days to 4 mo after birth) were studied by MRI under isoflurane anesthesia. Electrocardiogram-gated cine MRI was performed with an in-plane resolution of (78–117 μm)2. Temporal resolution per cine frame was 8.6 ms. MRI revealed cardiac anatomy in mice from all age groups with high temporal and spatial resolution. There was close correlation between MRI- and autopsy-determined left ventricular (LV) mass ( r = 0.95, SE of estimate = 9.5 mg). The increase of LV mass (range 9.6–101.3 mg), cardiac output (range 1.1–14.3 ml/min), and stroke volume (range 3.2–40.2 μl) with age could be quantified by MRI measurements. Ejection fraction and cardiac index did not change with aging. However, LV mass index decreased with increasing age ( P < 0.01). High-resolution MRI allows for accurate in vivo assessment of cardiac function in neonatal, juvenile, and adult mice. This method should be useful when applied in transgenic mouse models.

scholarly journals Thymosin-β4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction

2014 ◽  
Vol 307 (5) ◽  
pp. H741-H751 ◽  
Author(s):  
Hongmei Peng ◽  
Jiang Xu ◽  
Xiao-Ping Yang ◽  
Xiangguo Dai ◽  
Edward L. Peterson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cell Survival ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cardiac Rupture ◽  
Gelatinolytic Activity ◽  
P53 Expression

Thymosin-β4 (Tβ4) promotes cell survival, angiogenesis, and tissue regeneration and reduces inflammation. Cardiac rupture after myocardial infarction (MI) is mainly the consequence of excessive regional inflammation, whereas cardiac dysfunction after MI results from a massive cardiomyocyte loss and cardiac fibrosis. It is possible that Tβ4 reduces the incidence of cardiac rupture post-MI via anti-inflammatory actions and that it decreases adverse cardiac remodeling and improves cardiac function by promoting cardiac cell survival and cardiac repair. C57BL/6 mice were subjected to MI and treated with either vehicle or Tβ4 (1.6 mg·kg−1·day−1 ip via osmotic minipump) for 7 days or 5 wk. Mice were assessed for 1) cardiac remodeling and function by echocardiography; 2) inflammatory cell infiltration, capillary density, myocyte apoptosis, and interstitial collagen fraction histopathologically; 3) gelatinolytic activity by in situ zymography; and 4) expression of ICAM-1 and p53 by immunoblot analysis. Tβ4 reduced cardiac rupture that was associated with a decrease in the numbers of infiltrating inflammatory cells and apoptotic myocytes, a decrease in gelatinolytic activity and ICAM-1 and p53 expression, and an increase in the numbers of CD31-positive cells. Five-week treatment with Tβ4 ameliorated left ventricular dilation, improved cardiac function, markedly reduced interstitial collagen fraction, and increased capillary density. In a murine model of acute MI, Tβ4 not only decreased mortality rate as a result of cardiac rupture but also significantly improved cardiac function after MI. Thus, the use of Tβ4 could be explored as an alternative therapy in preventing cardiac rupture and restoring cardiac function in patients with MI.

scholarly journals Cardiac Hypertrophy and Fibrosis in the Metabolic Syndrome: A Role for Aldosterone and the Mineralocorticoid Receptor

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Eric E. Essick ◽  
Flora Sam
Keyword(s):  
Metabolic Syndrome ◽  
Cardiac Hypertrophy ◽  
Cross Talk ◽  
Mineralocorticoid Receptor ◽  
Ventricular Hypertrophy ◽  
Cardiac Fibrosis ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
The Metabolic Syndrome ◽  
Increased Risk

Obesity and hypertension, major risk factors for the metabolic syndrome, render individuals susceptible to an increased risk of cardiovascular complications, such as adverse cardiac remodeling and heart failure. There has been much investigation into the role that an increase in the renin-angiotensin-aldosterone system (RAAS) plays in the pathogenesis of metabolic syndrome and in particular, how aldosterone mediates left ventricular hypertrophy and increased cardiac fibrosis via its interaction with the mineralocorticoid receptor (MR). Here, we review the pertinent findings that link obesity with elevated aldosterone and the development of cardiac hypertrophy and fibrosis associated with the metabolic syndrome. These studies illustrate a complex cross-talk between adipose tissue, the heart, and the adrenal cortex. Furthermore, we discuss findings from our laboratory that suggest that cardiac hypertrophy and fibrosis in the metabolic syndrome may involve cross-talk between aldosterone and adipokines (such as adiponectin).

Comparison of isoproterenol and dobutamine in the induction of cardiac hypertrophy and fibrosis

Perfusion ◽  
2008 ◽  
Vol 23 (4) ◽  
pp. 231-235 ◽  
Author(s):  
M Anderson ◽  
D Moore ◽  
DF Larson
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Detrimental Effect ◽  
Chronic Administration ◽  
Atrial Size ◽  
Term Administration ◽  
And Function ◽  
Induce Heart Failure

Isoproterenol (Iso) was a clinical therapeutic that is now used as a research means for the induction of cardiac hypertrophy. Currently, dobutamine (Dob) has replaced Iso as the preferred inotropic β-adrenergic agent to wean patients from cardiopulmonary bypass and to sustain adequate cardiac function during the postoperative period. We sought to compare the cardiac structural and functional effects of long-term administration (7days) of Iso with Dob at a dose of 40μg/mouse/day in 12-week-old C57BL/6 female mice. Cardiac function was determined with transthoracic echo cardiography (ECHO) 24 hours after the last dose. Cardiac wet weights increased 33% and 24% in the Iso and Dob groups compared with controls ( p < 0.05). Dob and Iso significantly increased cardiac fibrosis and decreased cardiac function with chronic administration. Administration also resulted in increased left atrial size, suggesting that both Dob and Iso decreased LV compliance, but did not induce heart failure. In conclusion, chronic administration of Dob may have a detrimental effect on cardiac structure and function.

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