Echocardiographic assessment of cardiac function in diabeticdb/db and transgenic db/db-hGLUT4 mice

2002 ◽  
Vol 283 (3) ◽  
pp. H976-H982 ◽  
Author(s):  
Lisa M. Semeniuk ◽  
Albert J. Kryski ◽  
David L. Severson
Keyword(s):  
Cardiac Function ◽  
Diastolic Dysfunction ◽  
Glucose Transporter ◽  
Contractile Function ◽  
Systolic Function ◽  
Cardiac Metabolism ◽  
Flow Measurements ◽  
Echocardiographic Assessment ◽  
Fractional Shortening

Control db/+ and diabetic db/ db mice at 6 and 12 wk of age were subjected to echocardiography to determine whether contractile function was reduced in vivo and restored in transgenic db/ db-human glucose transporter 4 (hGLUT4) mice (12 wk old) in which cardiac metabolism has been normalized. Systolic function was unchanged in 6-wk-old db/ db mice, but fractional shortening and velocity of circumferential fiber shortening were reduced in 12-wk-old db/ db mice (43.8 ± 2.1% and 8.3 ± 0.5 circs/s, respectively) relative to db/+ control mice (59.5 ± 2.3% and 11.8 ± 0.4 circs/s, respectively). Doppler flow measurements were unchanged in 6-wk-old db/ db mice. The ratio of E and A transmitral flows was reduced from 3.56 ± 0.29 in db/+ mice to 2.40 ± 0.20 in 12-wk-old db/ dbmice, indicating diastolic dysfunction. Thus a diabetic cardiomyopathy with systolic and diastolic dysfunction was evident in 12-wk-old diabetic db/ db mice. Cardiac function was normalized in transgenic db/ db-hGLUT4 mice, indicating that altered cardiac metabolism can produce contractile dysfunction in diabetic db/ db hearts.

Long-term levosimendan treatment improves systolic function and myocardial relaxation in mice with cardiomyocyte-specific disruption of the Serca2 gene

2013 ◽  
Vol 115 (10) ◽  
pp. 1572-1580 ◽  
Author(s):  
Vigdis Hillestad ◽  
Frank Kramer ◽  
Stefan Golz ◽  
Andreas Knorr ◽  
Kristin B. Andersson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Function ◽  
Diastolic Dysfunction ◽  
Systolic Function ◽  
Cytosolic Calcium ◽  
Left Ventricular ◽  
Pressure Measurements ◽  
Human Heart Failure

In human heart failure (HF), reduced cardiac function has, at least partly, been ascribed to altered calcium homeostasis in cardiomyocytes. The effects of the calcium sensitizer levosimendan on diastolic dysfunction caused by reduced removal of calcium from cytosol in early diastole are not well known. In this study, we investigated the effect of long-term levosimendan treatment in a murine model of HF where the sarco(endo)plasmatic reticulum ATPase ( Serca) gene is specifically disrupted in the cardiomyocytes, leading to reduced removal of cytosolic calcium. After induction of Serca2 gene disruption, these mice develop marked diastolic dysfunction as well as impaired contractility. SERCA2 knockout (SERCA2KO) mice were treated with levosimendan or vehicle from the time of KO induction. At the 7-wk end point, cardiac function was assessed by echocardiography and pressure measurements. Vehicle-treated SERCA2KO mice showed significantly diminished left-ventricular (LV) contractility, as shown by decreased ejection fraction, stroke volume, and cardiac output. LV pressure measurements revealed a marked increase in the time constant (τ) of isovolumetric pressure decay, showing impaired relaxation. Levosimendan treatment significantly improved all three systolic parameters. Moreover, a significant reduction in τ toward normalization indicated improved relaxation. Gene-expression analysis, however, revealed an increase in genes related to production of the ECM in animals treated with levosimendan. In conclusion, long-term levosimendan treatment improves both contractility and relaxation in a heart-failure model with marked diastolic dysfunction due to reduced calcium transients. However, altered gene expression related to fibrosis was observed.

Abstract 791: A Critical Role for Bmper (BMP-binding Endothelial cell precursor-derived Regulator) in Cardiac Muscle Mass Regulation during Development and Pressure Overload Induced Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monte Willis ◽  
Rongqin Ren ◽  
Cam Patterson
Keyword(s):  
Cardiac Function ◽  
Cardiac Muscle ◽  
Muscle Mass ◽  
Cardiac Development ◽  
Critical Role ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Fractional Shortening

Bone morphogenetic proteins (BMPs) of the TGF-beta superfamily, have been implicated in multiple processes during cardiac development. Our laboratory recently described an unprecedented role for Bmper in antagonizing BMP-2, BMP-4, and BMP-6. To determine the role of Bmper on cardiac development in vivo, we created Bmper null (Bmper −/−) mice by replacing exons 1 and 2 with GFP. Since Bmper −/− mice are perinatally lethal, we determined pre-natal cardiac function of Bmper −/− mice in utero just before birth. By echocardiography, E18.5 Bmper −/− embryos had decreased cardiac function (24.2 +/− 8.1% fractional shortening) compared to Bmper +/− and Bmper +/+ siblings (52.2 +/− 1.6% fractional shortening) (N=4/group). To further characterize the role of Bmper on cardiac function in adult mice, we performed echocardiography on 8-week old male and female Bmper +/− and littermate control Bmper +/+. Bmper +/− mice had an approximately 15% decrease in anterior and posterior wall thickness compared to sibling Bmper +/+ mice at baseline (n=10/group). Cross-sectional areas of Bmper +/− cardiomyocytes were approximately 20% less than wild type controls, indicating cardiomyocyte hypoplasia in adult Bmper +/− mice at baseline. Histologically, no significant differences were identified in representative H&E and trichrome stained adult Bmper +/− and Bmper +/+ cardiac sections at baseline. To determine the effects of Bmper expression on the development of cardiac hypertrophy, both Bmper +/− and Bmper +/+ sibling controls underwent transaortic constriction (TAC), followed by weekly echocardiography. While a deficit was identified in Bmper +/− mice at baseline, both anterior and posterior wall thicknesses increased after TAC, such that identical wall thicknesses were identified in Bmper +/− and Bmper +/+ mice 1–4 weeks after TAC. Notably, cardiac function (fractional shortening %) and histological evaluation revealed no differences between Bmper +/− and Bmper +/+ any time after TAC. These studies identify for the first time that Bmper expression plays a critical role in regulating cardiac muscle mass during development, and that Bmper regulates the development of hypertrophy in response to pressure overload in vivo.

scholarly journals Diastolic Cardiac Function by MRI—Imaging Capabilities and Clinical Applications

Tomography ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 893-914
Author(s):  
El-Sayed H. Ibrahim ◽  
Jennifer Dennison ◽  
Luba Frank ◽  
Jadranka Stojanovska
Keyword(s):  
Cardiac Function ◽  
Diastolic Dysfunction ◽  
Systolic Function ◽  
Heart Diseases ◽  
Left Ventricular ◽  
Clinical Applications ◽  
Mri Imaging ◽  
Spatial And Temporal Patterns ◽  
Myocardial Relaxation ◽  
Diastolic Cardiac Function

Most cardiac studies focus on evaluating left ventricular (LV) systolic function. However, the assessment of diastolic cardiac function is becoming more appreciated, especially with the increasing prevalence of pathologies associated with diastolic dysfunction like heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction is an indication of abnormal mechanical properties of the myocardium, characterized by slow or delayed myocardial relaxation, abnormal LV distensibility, and/or impaired LV filling. Diastolic dysfunction has been shown to be associated with age and other cardiovascular risk factors such as hypertension and diabetes mellitus. In this context, cardiac magnetic resonance imaging (MRI) has the capability for differentiating between normal and abnormal myocardial relaxation patterns, and therefore offers the prospect of early detection of diastolic dysfunction. Although diastolic cardiac function can be assessed from the ratio between early and atrial filling peaks (E/A ratio), measuring different parameters of heart contractility during diastole allows for evaluating spatial and temporal patterns of cardiac function with the potential for illustrating subtle changes related to age, gender, or other differences among different patient populations. In this article, we review different MRI techniques for evaluating diastolic function along with clinical applications and findings in different heart diseases.

scholarly journals Alterations in Glucose Metabolism During the Transition to Heart Failure: The Contribution of UCP-2

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 552 ◽  
Author(s):  
Hanna Sarah Kutsche ◽  
Rolf Schreckenberg ◽  
Martin Weber ◽  
Christine Hirschhäuser ◽  
Susanne Rohrbach ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Contractile Function ◽  
Uncoupling Protein ◽  
Left Ventricular ◽  
Mitochondrial Uncoupling ◽  
Glut 4

The cardiac expression of the mitochondrial uncoupling protein (UCP)-2 is increased in patients with heart failure. However, the underlying causes as well as the possible consequences of these alterations during the transition from hypertrophy to heart failure are still unclear. To investigate the role of UCP-2 mechanistically, expression of UCP-2 was silenced by small interfering RNA in adult rat ventricular cardiomyocytes. We demonstrate that a downregulation of UCP-2 by siRNA in cardiomyocytes preserves contractile function in the presence of angiotensin II. Furthermore, silencing of UCP-2 was associated with an upregulation of glucose transporter type (Glut)-4, increased glucose uptake, and reduced intracellular lactate levels, indicating improvement of the oxidative glucose metabolism. To study this adaptation in vivo, spontaneously hypertensive rats served as a model for cardiac hypertrophy due to pressure overload. During compensatory hypertrophy, we found low UCP-2 levels with an upregulation of Glut-4, while the decompensatory state with impaired function was associated with an increase of UCP-2 and reduced Glut-4 expression. By blocking the aldosterone receptor with spironolactone, both cardiac function as well as UCP-2 and Glut-4 expression levels of the compensated phase could be preserved. Furthermore, we were able to confirm this by left ventricular (LV) biopsies of patients with end-stage heart failure. The results of this study show that UCP-2 seems to impact the cardiac glucose metabolism during the transition from hypertrophy to failure by affecting glucose uptake through Glut-4. We suggest that the failing heart could benefit from low UCP-2 levels by improving the efficiency of glucose oxidation. For this reason, UCP-2 inhibition might be a promising therapeutic strategy to prevent the development of heart failure.

Alteration of mitochondrial function in a model of chronic ischemia in vivo in rat heart

2002 ◽  
Vol 282 (3) ◽  
pp. H821-H831 ◽  
Author(s):  
Sihem Boudina ◽  
Muriel N. Laclau ◽  
Liliane Tariosse ◽  
Danièle Daret ◽  
Gérard Gouverneur ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Mitochondrial Function ◽  
Contractile Function ◽  
Systolic Function ◽  
Rate Pressure Product ◽  
Maximal Velocity ◽  
Chronic Ischemia ◽  
Membrane Rupture

The aim of this study was to investigate mitochondrial alterations in an animal model of chronic myocardial ischemia in rats obtained by surgical constriction of the left coronary artery. Resting coronary blood flow was measured using the fluorescent microsphere technique. Contractile function, defined by rate-pressure product, and myocardial oxygen consumption were measured in a Langendorff preparation. The mitochondrial function was evaluated on permeabilized skinned fibers. Three weeks after surgery, ischemic hearts showed a significant decrease in coronary blood flow compared with sham. Hemodynamic measurements showed a significant systolic and diastolic dysfunction. Alterations in mitochondrial function in ischemic hearts were mainly characterized by a significant decrease in the maximal velocity and apparent half-saturation constant for ADP, loss of the stimulatory effect of creatine, and a stimulatory effect of exogenous cytochrome c. These functional alterations were supported by structural alterations characterized by mitochondrial clustering and swelling associated with membrane rupture. We conclude that the alterations in systolic function after chronic ischemia are supported by severe modifications of mitochondrial structure and function.

Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function

2009 ◽  
Vol 297 (6) ◽  
pp. H2096-H2108 ◽  
Author(s):  
Ratnadeep Basu ◽  
Gavin Y. Oudit ◽  
Xiuhua Wang ◽  
Liyan Zhang ◽  
John R. Ussher ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Ex Vivo ◽  
Systolic Function ◽  
Doppler Imaging ◽  
Hemodynamic Measurements ◽  
Long Chain

Diabetic cardiomyopathy is an important contributor to diastolic and systolic heart failure. We examined the nature and mechanism of the cardiomyopathy in Akita ( Ins2WT/C96Y) mice, a model of genetic nonobese type 1 diabetes that recapitulates human type 1 diabetes. Cardiac function was evaluated in male Ins2WT/C96Y and their littermate control ( Ins2WT/WT) mice using echocardiography and tissue Doppler imaging, in vivo hemodynamic measurements, as well as ex vivo working heart preparation. At 3 and 6 mo of age, Ins2WT/C96Y mice exhibited preserved cardiac systolic function compared with Ins2WT/WT mice, as evaluated by ejection fraction, fractional shortening, left ventricular (LV) end-systolic pressure and maximum rate of increase in LV pressure in vivo, cardiac work, cardiac power, and rate-pressure product ex vivo. Despite the unaltered systolic function, Ins2WT/C96Y mice exhibited significant and progressive diastolic dysfunction at 3 and 6 mo of age compared with Ins2WT/WT mice as assessed by tissue and pulse Doppler imaging (E-wave velocity, isovolumetric relaxation time) and by in vivo hemodynamic measurements (LV end-diastolic pressure, time constant of LV relaxation, and maximum rate of decrease in LV pressure). We found no evidence of myocardial hypertrophy or fibrosis in the Ins2WT/C96Y myocardium. Consistent with the lack of fibrosis, expression of procollagen-α type I, procollagen-α type III, and fibronectin were not increased in these hearts. Ins2WT/C96Y hearts showed significantly reduced sarcoplasmic reticulum Ca2+-ATPase 2a (cardiac sarcoplasmic reticulum Ca2+ pump) levels, elevated β-myosin heavy chain isoform, increased long-chain fatty acids, and triacylglycerol with evidence of lipotoxicity, as indicated by a significant rise in ceramide, diacylglycerol, and lipid deposits in the myocardium. Consistent with metabolic perturbation, and a switch to fatty acid oxidation from glucose oxidation in Ins2WT/C96Y hearts, expression of mitochondrial long-chain acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase isoform 4 were increased. Insulin treatment reversed the diastolic dysfunction, the elevated B-type natriuretic peptide and β-myosin heavy chain, and the reduced sarcoplasmic reticulum Ca2+-ATPase 2a levels with abolition of cardiac lipotoxicity. We conclude that early type 1 diabetic cardiomyopathy is characterized by diastolic dysfunction associated with lipotoxic cardiomyopathy with preserved systolic function in the absence of interstitial fibrosis and hypertrophy.

Short-term in vivo inhibition of nitric oxide synthase with L-NAME influences the contractile function of single left ventricular myocytes in rats

2011 ◽  
Vol 89 (4) ◽  
pp. 305-310 ◽  
Author(s):  
Wellington Lunz ◽  
Antônio José Natali ◽  
Miguel Araújo Carneiro ◽  
Luciano dos Santos Aggum Capettini ◽  
Marcelo Perim Baldo ◽  
...  
Keyword(s):  
Maximum Rate ◽  
Ventricular Myocytes ◽  
Contractile Function ◽  
Left Ventricular ◽  
Regulatory Proteins ◽  
Hemodynamic Parameters ◽  
Short Term ◽  
Oxide Synthase ◽  
Fractional Shortening

The main purpose of this study was to investigate the effects of short-term L-NAME treatment on the contractile function of left ventricle (LV) myocytes and the expression of proteins related to Ca2+ homeostasis. Data from Wistar rats treated with L-NAME (L group, n = 20; 0.7 g/L in drinking water; 7 days) were compared with results from untreated controls (C group, n = 20). Cardiomyocytes from the L group showed increased (p < 0.05) fractional shortening (23%) and maximum rate of shortening (20%) compared with the C group. LV from the L group also showed increased (p < 0.05) expression of the ryanodine receptor 2 and Na+/Ca2+ exchanger proteins (76% and 83%, respectively; p < 0.05). However, the L and C groups showed similar in vivo hemodynamic parameters of cardiac function. In conclusion, short-term NOS inhibition determines an increased expression of Ca2+ regulatory proteins, which contributes to improving cardiomyocyte contractile function, preserving left ventricular function.

scholarly journals Extracellular SPARC improves cardiomyocyte contraction during health and disease

2018 ◽  
Author(s):  
Sophie Deckx ◽  
Daniel M. Johnson ◽  
Marieke Rienks ◽  
Paolo Carai ◽  
Elza van Deel ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Matrix Protein ◽  
Contractile Function ◽  
Ex Vivo ◽  
Cardiac Fibroblasts ◽  
Cardiac Injury ◽  
Coxsackie Virus ◽  
Extracellular Matrix Protein

Secreted protein acidic and rich in cysteine (SPARC) is a non-structural extracellular matrix protein that regulates interactions between the matrix and neighboring cells. In the cardiovascular system, it is expressed by cardiac fibroblasts, endothelial cells, and in lower levels by ventricular cardiomyocytes. SPARC expression levels are increased upon myocardial injury and also during hypertrophy and fibrosis. We have previously shown that SPARC improves cardiac function after myocardial infarction by regulating post-synthetic procollagen processing, however whether SPARC directly affects cardiomyocyte contraction is still unknown. In this study we demonstrate a novel inotropic function for extracellular SPARC in the healthy heart as well as in the diseased state after myocarditis-induced cardiac dysfunction. We demonstrate SPARC presence on the cardiomyocyte membrane where it is co-localized with the integrin-beta1 and the integrin-linked kinase. Moreover, extracellular SPARC directly improves cardiomyocyte cell shortening ex vivo and cardiac function in vivo, both in healthy myocardium and during coxsackie virus-induced cardiac dysfunction. In conclusion, we demonstrate a novel inotropic function for SPARC in the heart, with a potential therapeutic application when myocyte contractile function is diminished such as that caused by a myocarditis-related cardiac injury.

scholarly journals Stable Isotopes for Tracing Cardiac Metabolism in Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Anja Karlstaedt
Keyword(s):  
Cardiovascular Disease ◽  
Stable Isotope ◽  
Isotope Labeling ◽  
Contractile Function ◽  
Ex Vivo ◽  
Cardiac Metabolism ◽  
Metabolic Adaptation ◽  
Cardiovascular Research ◽  
Metabolic Remodeling

Although metabolic remodeling during cardiovascular diseases has been well-recognized for decades, the recent development of analytical platforms and mathematical tools has driven the emergence of assessing cardiac metabolism using tracers. Metabolism is a critical component of cellular functions and adaptation to stress. The pathogenesis of cardiovascular disease involves metabolic adaptation to maintain cardiac contractile function even in advanced disease stages. Stable-isotope tracer measurements are a powerful tool for measuring flux distributions at the whole organism level and assessing metabolic changes at a systems level in vivo. The goal of this review is to summarize techniques and concepts for in vivo or ex vivo stable isotope labeling in cardiovascular research, to highlight mathematical concepts and their limitations, to describe analytical methods at the tissue and single-cell level, and to discuss opportunities to leverage metabolic models to address important mechanistic questions relevant to all patients with cardiovascular disease.

Hypoxic pHi and function modulation by Na+/H+ exchange and alpha-adrenoreceptor inhibition in heart in vivo

1997 ◽  
Vol 272 (6) ◽  
pp. H2664-H2670 ◽  
Author(s):  
M. A. Portman ◽  
Y. Xiao ◽  
B. G. Broers ◽  
X. H. Ning
Keyword(s):  
Cardiac Function ◽  
Contractile Function ◽  
High Energy ◽  
Left Ventricular ◽  
Resonance Spectroscopy ◽  
Cardiac Contractile Function ◽  
Significant Drop ◽  
And Function ◽  
Phi Regulation

Regulation of intracellular pH (pHi) may contribute to maintenance of cardiac contractile function during graded hypoxia in vivo. To test this hypothesis, we disturbed pHi regulation in vivo using two approaches: alpha-adrenoreceptor antagonism with phentolamine (1 mg/kg) (Phen; n = 9); and Na+/H+ exchange inhibition with HOE-642 (2 mg/kg; n = 6) before graded hypoxia in open-chest sheep. Hemodynamic parameters including left ventricular maximal pressure development (dP/dtmax) cardiac index (CI), and left ventricular power were monitored continuously and simultaneously with high-energy phosphate levels and pHi, measured with 31P nuclear magnetic resonance spectroscopy in Phen, HOE-642, and control (Con; n = 9). In subgroups (n = 6) in Con and Phen, coronary flow, myocardial oxygen consumption (MVO2), and lactate uptake were also measured. During hypoxia, the functional parameters left ventricular dP/dtmax, CI, and left ventricular power decreased significantly compared with baseline and Con values. These decreases were preceded by a significant drop (P < 0.05) in pHi from 7.10 +/- 0.04 to 6.69 +/- 0.05 in Phen and corresponded temporally to a pHi drop from 7.10 +/- 0.02 to 6.77 +/- 0.03 in HOE-642. Decreases in pHi in Phen were not preceded by decreases in cardiac function or MVO2. In contrast, cardiac function parameters increased significantly in Con, whereas no significant pHi decrease occurred (7.07 +/- 0.03 to 6.98 +/- 0.04). We conclude that these data indicate that pHi regulation can be disrupted through alpha-adrenergic antagonism or Na+/H(+)-exchange inhibition in vivo. These studies demonstrate that pHi regulation performs a role in the modulation of cardiac function during hypoxia in vivo.

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