scholarly journals Sirtuin 5 levels are limiting in preserving cardiac function and suppressing fibrosis in response to pressure overload

2021 ◽  
Author(s):  
Angela H Guo ◽  
Rachael K Baliira ◽  
Mary E Skinner ◽  
Surinder Kumar ◽  
Anthony Andren ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Systolic Function ◽  
Cardiac Contractility ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Acid Oxidation ◽  
Limiting Factor ◽  
Loss Of Function ◽  
Metabolic Switch ◽  
Ventricular Fibrosis

Heart failure (HF) is defined as an inability of the heart to pump blood adequately to meet the body's metabolic demands. HF with reduced systolic function is characterized by cardiac hypertrophy, ventricular fibrosis and remodeling, and decreased cardiac contractility, leading to cardiac functional impairment and death. Transverse aortic constriction (TAC) is a well-established model for inducing hypertrophy and HF in rodents. Mice globally deficient in sirtuin 5 (SIRT5), a NAD+-dependent deacylase, are hypersensitive to cardiac stress and display increased mortality after TAC. Prior studies assessing SIRT5 functions in the heart have all employed loss-of-function approaches. In this study, we generated SIRT5 overexpressing (SIRT5OE) mice, and evaluated their response to chronic pressure overload induced by TAC. Compared to littermate controls, SIRT5OE mice were protected from left ventricular dilation and impaired ejection fraction, adverse functional consequences of TAC. Transcriptomic analyses revealed that SIRT5 suppresses key HF sequelae, including the metabolic switch from fatty acid oxidation to glycolysis, immune activation, and increased fibrotic signaling. We conclude that SIRT5 is a limiting factor in the preservation of cardiac function in response to experimental pressure overload.

Abstract P511: Sirtuin 5 Overexpression Protects Against Pressure Overload-Induced Ventricular Dysfunction

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Hanjia Guo ◽  
Rachael Baliirra ◽  
Mary Skinner ◽  
Surinder Kumar ◽  
Shaday Michan ◽  
...  
Keyword(s):  
Contractile Function ◽  
Systolic Dysfunction ◽  
Pressure Overload ◽  
The Body ◽  
Acid Oxidation ◽  
Limiting Factor ◽  
Loss Of Function ◽  
Cardiac Contractile Function ◽  
Metabolic Switch ◽  
Compensation Mechanisms

Heart failure (HF) is defined as an inability of the heart to pump blood sufficiently to meet the metabolic demands of the body. HF with systolic dysfunction is caused by a progressive decline in contractile function and chronic hemodynamic overload, and characterized by ventricular hypertrophy and remodeling, neurohormonal compensation mechanisms, and myocardial damage. Transverse aortic constriction (TAC) is a well-established model for inducing hypertrophy and HF in rodents. Mice globally deficient in sirtuin 5 (SIRT5), a NAD + -dependent deacylase, are hypersensitive to cardiac stress and display increased mortality after TAC. Prior studies assessing SIRT5 functions in the heart have all employed loss-of-function approaches. In this study, we generated SIRT5 overexpressing (SIRT5OE) mice, and evaluated their response to chronic pressure overload using TAC. Compared to littermate controls, elevated SIRT5 levels promoted maintenance of cardiac contractile function after 4 weeks of pressure overload, at which point control mice had developed systolic dysfunction, characterized by decreased EF, coupled with ventricular dilation, remodeling and fibrosis. Transcriptomic analysis revealed that SIRT5 suppresses key HF sequelae, including metabolic switch from fatty acid oxidation to glycolysis and immune activation ( i.e., TGFβ, IL6, Renin-Angiotensin, and NFAT, and fibrotic signaling pathways). We conclude that SIRT5 is a limiting factor in the preservation of cardiac function in response to experimental pressure overload.

Abstract 16200: Chronic Central Nervous System Actions of Leptin Protect Against Myocardial Ischemia/reperfusion Injury

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ana Carolina Mieko Omoto ◽  
Jussara M do Carmo ◽  
Elizabeth R Flynn ◽  
Sydney P Moak ◽  
Xuan Li ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cardiac Function ◽  
Systolic Function ◽  
Ischemia Reperfusion ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Histological Evaluation ◽  
Acid Oxidation ◽  
Collagen Deposition

While myocardial reperfusion is the most effective therapy to reduce mortality after myocardial infarction, it can paradoxically exacerbate ischemic injury. We recently showed that leptin, via its actions on the central nervous system (CNS), improved left ventricular function in a model of heart failure induced by permanent ligation of the left anterior coronary artery (LAD). To investigate whether leptin also protects the heart against ischemia/reperfusion (I/R) injury via its actions in the CNS, we instrumented female Wistar rats (15 weeks of age) with an intracerebroventricular (ICV) cannula into the lateral ventricle, and after 7 days of recovery and baseline assessment of cardiac function by echocardiography (VisualSonics VEVO-3100®), myocardial I/R was induced by temporary LAD ligation (60 min). Vehicle (saline, 0.5 μL/hr, n=6) or leptin (15 μg/day, n=7) were infused ICV for 28 consecutive days starting 20 min after reperfusion using osmotic minipump connected to the ICV cannula. Echocardiographic assessment of cardiac function was performed every week and at the end of the 4 th week of treatment, the heart was collected and processed for protein analysis and histological evaluation of infarct size and collagen deposition. Compared to vehicle treatment, chronic ICV leptin infusion significantly reduced infarcted area (21±2 vs. 37±4 %), septal collagen deposition (2.2±0.2 vs. 4.0±0.7 %), and markedly attenuated systolic dysfunction as evidenced by increased ejection fraction 4 weeks post I/R (59±1 vs. 30±2%), stroke volume (296±19 vs. 159±8 μL) and cardiac output (108±5 vs.63±4 μL/min). ICV leptin infusion also prevented the increase in left atrium to aorta diameter ratio (1.5±0.1 vs. 2±0.1 mm), an index of cardiac congestion. In addition, we found a 2-fold increase in the ratio of phospho-acetyl-CoA carboxylase (p-ACC) to total ACC protein expression, a marker of fatty acid oxidation, in hearts of leptin-treated rats compared with vehicle infusion. These results indicate that leptin exerts powerful beneficial CNS-mediated effects on the heart that improve systolic function and protect the myocardium against I/R injury. Our results also suggest that these beneficial actions may involve improved myocardial bioenergetics.

Regional Left Ventricular Systolic Function in Relation to the Cavity Geometry in Patients With Chronic Right Ventricular Pressure Overload

Circulation ◽  
1995 ◽  
Vol 91 (9) ◽  
pp. 2359-2370 ◽  
Author(s):  
Sheng-Jing Dong ◽  
Adrian P. Crawley ◽  
John H. MacGregor ◽  
Yael Fisher Petrank ◽  
Dale W. Bergman ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Systolic Function ◽  
Pressure Overload ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Ventricular Systolic Function

Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice

2001 ◽  
Vol 281 (5) ◽  
pp. H1938-H1945 ◽  
Author(s):  
Chari Y. T. Hart ◽  
John C. Burnett ◽  
Margaret M. Redfield
Keyword(s):  
Cardiac Function ◽  
Diastolic Pressure ◽  
Systolic Function ◽  
Pressure Rise ◽  
Left Ventricular ◽  
Lv Function ◽  
Ketamine Anesthesia ◽  
The Difference ◽  
And Function ◽  
Derivatives Of

Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (τ), and the first derivatives of LV pressure rise and fall (dP/d t max and dP/d t min, respectively). During echocardiography, HR was lower in XK than AV mice (250 ± 14 beats/min in XK vs. 453 ± 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 ± 0.08 mm in XK vs. 3.8 ± 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 ± 1.2% in XK vs. 40 ± 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 ± 24 beats/min) and XK (342 ± 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 ± 5 vs. 6.2 ± 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/d t max: 4,402 ± 798 vs. 8,250 ± 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (τ: 23 ± 2 vs. 14 ± 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in the mouse.

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 51: Ambulatory Blood Pressure Phenotype And Cardiovascular Risk In Youth: The Ship-ahoy Study

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Joseph T Flynn ◽  
Philip Khoury ◽  
Joshua A Samuels ◽  
Marc B Lande ◽  
Kevin Meyers ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Function ◽  
Linear Models ◽  
Independent Predictor ◽  
Systolic Function ◽  
Left Ventricular ◽  
Cvd Risk ◽  
Oscillometric Device ◽  
Echocardiographic Parameters ◽  
Relationship Of

We investigated whether blood pressure (BP) phenotype based on clinic & 24-hour ambulatory BP (ABP) was associated with intermediate markers of cardiovascular disease (CVD) in 374 adolescents enrolled in a study of the relationship of BP to CV risk. Clinic BP was measured by auscultation and categorized using the 2017 AAP guideline. ABP was measured for 24 hours by an oscillometric device and analyzed using the adult ABP wake SBP cut-point (130 mmHg). This created 4 BP phenotype groups: normal BP (n=224), white coat hypertensive (n=48), ambulatory hypertensive (n=57) & masked hypertensive (n=45). Echocardiographic parameters & carotid-femoral pulse wave velocity (PWVcf) were measured to assess CVD risk. Left ventricular mass (LVM) was lowest in the normal BP group, whereas multiple measures of cardiac function and PWVcf were worse in the masked and ambulatory hypertensive groups: Generalized linear models adjusted for body mass index (BMI) were constructed to examine the associations between BP phenotype and the measured CVD variables. ABP phenotype was an independent predictor of LVM, diastolic and systolic function and PWVcf in the unadjusted model. ABP phenotype remained significantly associated with diastolic function (E/e’, e’/a’), systolic function (ejection fraction) and increased arterial stiffness (PWVcf) after adjustment for BMI percentile (all p<=0.05). We conclude that BP phenotype is an independent predictor of markers of increased CVD risk in adolescents, including impaired cardiac function and increased vascular stiffness. ABP monitoring has an important role in CVD risk assessment in youth.

Muscle metabolism and cardiac function of the myopathic hamster following training

1977 ◽  
Vol 43 (6) ◽  
pp. 936-941 ◽  
Author(s):  
W. L. Sembrowich ◽  
M. B. Knudson ◽  
P. D. Gollnick
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Function ◽  
Myocardial Function ◽  
Cardiac Contractility ◽  
Muscle Metabolism ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Succinate Dehydrogenase Activity ◽  
Positive Effect

The effect of 18 wk of treadmill running on skeletal muscle metabolism and myocardial function of normal and myopathic hamsters was examined. BIO 14.6 hamsters could tolerate an exercise intensity of about 18 m/min for 40 min, 5 days/wk. Further increases in speed or number of bouts per day resulted in a falloff in performance. Normal hamsters could tolerate higher speeds and longer exercise bouts. Exercise did not change the severity of lesions of either the heart or skeletal muscle of the myopathic hamsters. A training effect was evidenced by increased succinate dehydrogenase activity in the soleus muscle. Cardiac function was evaluated as contractility measured from left ventricular pressure curves and expressed as (dP/dt)/kP. The results suggested that cardiac contractility was not as severely depressed in the trained BIO 14.6 strain of hamsters as in nontrained controls. However, (dP/dt)/kP was lower in the trained myopathic animals than in normal hamsters. ATP, CP, and glycogen levels were lower in myopathic hamsters with the lowest values occurring in the trained group. These data demonstrate that the BIO 14.6 strain of hamster can tolerate exercise training and that such training may have a positive effect on cardiac function.

Effect of human urotensin-II infusion on hemodynamics and cardiac function

2003 ◽  
Vol 81 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Ghada S Hassan ◽  
Fazila Chouiali ◽  
Takayuki Saito ◽  
Fu Hu ◽  
Stephen A Douglas ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diastolic Pressure ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Urotensin Ii ◽  
Ventricular Systolic Pressure ◽  
Wide Range ◽  
Dose Dependent Decrease

Recent studies have shown that the vasoactive peptide urotensin-II (U-II) exerts a wide range of action on the cardiovascular system of various species. In the present study, we determined the in vivo effects of U-II on basal hemodynamics and cardiac function in the anesthetized intact rat. Intravenous bolus injection of human U-II resulted in a dose-dependent decrease in mean arterial pressure and left ventricular systolic pressure. Cardiac contractility represented by ±dP/dt was decreased after injection of U-II. However, there was no significant change in heart rate or diastolic pressure. The present study suggests that upregulation of myocardial U-II may contribute to impaired myocardial function in disease conditions such as congestive heart failure.Key words: urotensin-II, rat, infusion, heart.

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.

Abstract 14952: Hemodynamic Comparison of Left Ventricular Function in Pressure Overload- versus Volume Overload-Induced Heart Failure Models by Invasive Pressure-Volume Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mihály Ruppert ◽  
Christian Karime ◽  
Alex A Sayour ◽  
Attila Oláh ◽  
Dávid Nagy ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Function ◽  
Pressure Overload ◽  
Volume Overload ◽  
Detailed Comparison ◽  
Left Ventricular ◽  
Lv Function ◽  
Arterial Elastance ◽  
Lv Remodeling ◽  
Av Shunt

Introduction: Both sustained left ventricular (LV) pressure overload (PO) and volume overload (VO) induces LV remodeling and eventually development of heart failure (HF). Using rat models, the present study aimed to provide a detailed comparison of distinct aspects of LV function in PO- and VO-induced HF. Methods: PO and VO was induced by transverse aortic constriction (TAC, n=12) and aortocaval shunt (AV-shunt, n=12) creation respectively. Controls underwent corresponding sham operations (n=11). LV remodeling was characterized by echocardiography, histology, qRT PCR, and western blot. LV function was assessed by invasive pressure-volume (P-V) analysis. Results: Both sustained PO and VO resulted in the development of HF, as evidenced by increased LV BNP mRNA expression, pulmonary edema, and characteristic symptoms. While the extent of LV hypertrophy was comparable between the HF models, PO induced concentric while VO evoked eccentric LV remodeling. P-V analysis revealed impaired systolic function in both HF models. Accordingly, decreased ejection fraction and impaired ventriculo-arterial coupling (calculated as the ratio of arterial elastance/LV contractility [VAC]: 0.38±0.05 vs. 1.30±0.13, ShamTAC vs. TAC and 0.52±0.08 vs. 1.17±0.13, ShamAV-Shunt vs. AV-shunt; p<0.05) was detected in both HF models. However, in case of VO the severely reduced LV contractility (slope of end-systolic P-V relationship: 1.79±0.19 vs. 0.52±0.06, ShamAV-Shunt vs. AV-shunt, p<0.05 and 2.14±0.28 vs. 2.03±0.21, ShamTAC vs. TAC p>0.05) underpinned the contractility-afterload mismatch, while in case of PO the increased afterload (arterial elastance: 0.77±0.07 vs. 2.64±0.28, ShamTAC vs. TAC and 0.80±0.07 vs. 0.54±0.05, ShamAV-Shunt vs. AV-shunt; p<0.05) was the main determinant. Furthermore, prolongation of active relaxation occurred to a greater extent in case of PO. In addition, increased myocardial stiffness was only observed in PO-induced HF. Conclusion: Systolic function was reduced in both HF models. However, different factors underpinned the impaired VAC in case of VO (reduced LV contractility) and PO (increased arterial elastance). Furthermore, although diastolic function deteriorated in both models, it occurred to a greater extent in case of PO.

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