scholarly journals Quantitative trait loci associated with angiotensin II and high-salt diet induced acute decompensated heart failure in Balb/CJ mice

2019 ◽  
Vol 51 (7) ◽  
pp. 279-289
Author(s):  
Mediha Becirovic-Agic ◽  
Sofia Jönsson ◽  
Michael Hultström
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Function ◽  
Quantitative Trait ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet ◽  
Filial Generation

Genetic background of different mouse strains determines their susceptibility to disease. We have previously shown that Balb/CJ and C57BL/6J mice develop cardiac hypertrophy to the same degree when treated with a combination of angiotensin II and high-salt diet (ANG II+Salt), but only Balb/CJ show impaired cardiac function associated with edema development and substantial mortality. We hypothesized that the different response to ANG II+Salt is due to the different genetic backgrounds of Balb/CJ and C57BL/6J. To address this we performed quantitative trait locus (QTL) mapping of second filial generation (F2) of mice derived from a backcross between Balb/CJ and first filial generation (F1) of mice. Cardiac function was measured with echocardiography, glomerular filtration rate using FITC-inulin clearance, fluid and electrolyte balance in metabolic cages, and blood pressure with tail-cuff at baseline and on the fourth day of treatment with ANG II+Salt. A total of nine QTLs were found to be linked to different phenotypes in ANG II+Salt-treated F2 mice. A QTL on chromosome 3 was linked to cardiac output, and a QTL on chromosome 12 was linked to isovolumic relaxation time. QTLs on chromosome 2 and 3 were linked to urine excretion and sodium excretion. Eight genes located at the different QTLs contained coding nonsynonymous SNPs published in the mouse genome database that differ between Balb/CJ and C57BL/6J. In conclusion, ANG II+Salt-induced acute decompensation in Balb/CJ is genetically linked to several QTLs, indicating a multifaceted phenotype. The present study identified potential candidate genes that may represent important pathways in acute decompensated heart failure.

scholarly journals Time course of decompensation after angiotensin II and high-salt diet in Balb/CJ mice suggests pulmonary hypertension-induced cardiorenal syndrome

2019 ◽  
Vol 316 (5) ◽  
pp. R563-R570 ◽  
Author(s):  
Mediha Becirovic-Agic ◽  
Sofia Jönsson ◽  
Maria K. Tveitarås ◽  
Trude Skogstrand ◽  
Tine V. Karlsen ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Angiotensin Ii ◽  
Cardiac Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
High Salt ◽  
Ang Ii ◽  
Salt Treatment ◽  
High Salt Diet ◽  
Salt Diet

The genetic background of a mouse strain determines its susceptibility to disease. C57BL/6J and Balb/CJ are two widely used inbred mouse strains that we found react dramatically differently to angiotensin II and high-salt diet (ANG II + Salt). Balb/CJ show increased mortality associated with anuria and edema formation while C57BL/6J develop arterial hypertension but do not decompensate and die. Clinical symptoms of heart failure in Balb/CJ mice gave the hypothesis that ANG II + Salt impairs cardiac function and induces cardiac remodeling in male Balb/CJ but not in male C57BL/6J mice. To test this hypothesis, we measured cardiac function using echocardiography before treatment and every day for 7 days during treatment with ANG II + Salt. Interestingly, pulsed wave Doppler of pulmonary artery flow indicated increased pulmonary vascular resistance and right ventricle systolic pressure in Balb/CJ mice, already 24 h after ANG II + Salt treatment was started. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Furthermore, Balb/CJ exhibited lower cardiac output compared with C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during ANG II + Salt treatment but did not differ between the strains. In conclusion, ANG II + Salt treatment causes early restriction of pulmonary flow and reduced left ventricular filling and cardiac output in Balb/CJ, which results in fluid retention and peripheral edema. This makes Balb/CJ a potential model to study the adaptive capacity of the heart for identifying new disease mechanisms and drug targets.

Abstract 14287: Ang II-induced Pathological Autophagy is Inhibited by IL-10 via Akt Dependent Inhibition of Beclin 1 in Mice Heart

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Suresh K Verma ◽  
Prasanna Krishnamurthy ◽  
Venkata N Girikipathi ◽  
Tatiana Abramova ◽  
Anna Gumpert ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Chronic Heart Failure ◽  
Cardiac Function ◽  
Beclin 1 ◽  
Neonatal Rat ◽  
Autophagic Flux ◽  
Physical Interaction ◽  
Ang Ii

Although, autophagy is an essential cellular salvage process to maintain cellular homeostasis, pathological autophagy can lead to cardiac abnormalities and ultimately heart failure. Therefore, a tight regulation on autophagic process would be important to treat chronic heart failure. Previously, we have shown that IL-10 strongly improved cardiac function in chronic heart failure models, but the role of IL-10 in regulation of pathological autophagy is not yet investigated. We tested the hypothesis that IL-10 inhibits angiotensin II-induced pathological autophagy and thus improved cardiac function. Pathological autophagy was induced in wild type (WT) and IL10-knockout mice by angiotensin II infusion. Ang II-induced left ventricular dysfunction and hypertrophic remodeling were accentuated in IL-10 KO mice compared to WT mice. IL-10 KO mice showed exaggerated autophagy with reduced AKT phosphorylation. In neonatal rat ventricular cardiomyocytes, Ang II activated beclin1 and LC3 levels and inhibited AKT/mTORC1 and AKT-Bcl2 signaling. IL-10 inhibited Ang II-induced autophagic marker proteins. Additionally, IL-10 restored Ang II effects on AKT/mTORC1 and AKT-Bcl2 signaling. Both pharmacological/molecular inhibition of AKT via PI3K inhibitor (LY290002) or Akt siRNA, attenuated IL-10 effects on the Ang II-induced pathological autophagy, confirming that IL-10 mediated regulation of pathological autophagy is AKT dependent. Similar results were observed with mTORC1 inhibitor rapamycin. Chloroquine (a lysosome inhibitor) strongly inhibits Ang II-induced autophagic flux. However, chloroquine did not affect IL-10 effects on autophagic flux, suggesting that IL-10 inhibits stress-induced pathological autophagy. Finally, as physical interaction of Bcl2 with beclin 1 is important to inhibit autophagy and IL-10 is strong activator of Bcl2, we performed immunoprecipitation experiment. Immunoprecipitation data suggested that Ang II disrupt the physical interaction of beclin 1 with Bcl2 and IL-10 reestablished this physical interaction to reduce autophagy. Our data give a novel role of IL-10 in regulation of pathological autophagy and thus can act as a potential therapeutic molecule in treatment of chronic heart disease.

scholarly journals Development and Validation of a Prediction Model for Irreversible Worsened Cardiac Function in Patients With Acute Decompensated Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Lei Wang ◽  
Yun-Tao Zhao
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Prediction Model ◽  
Acute Decompensated Heart Failure ◽  
Nyha Class ◽  
Decompensated Heart Failure ◽  
Study Data ◽  
Left Ventricular ◽  
Lasso Regression ◽  
Multivariable Logistic Regression Model

Background: Irreversible worsening of cardiac function is an adverse event associated with significant morbidity among patients with acute decompensated heart failure (ADHF). We aimed to develop a parsimonious model which is simple to use in clinical settings for the prediction of the risk of irreversible worsening of cardiac function.Methods: A total of 871 ADHF patients were enrolled in this study. Data for each patient were collected from the medical records. Irreversible worsening of cardiac function included cardiac death within 30-days of patient hospitalization, implantation of a left ventricular assistance device, or emergency heart transplantation. We performed LASSO regression for variable selection to derive a multivariable logistic regression model. Five candidate predictors were selected to derive the final prediction model. The prediction model was verified using C-statistics, calibration curve, and decision curve.Results: Irreversible worsening of cardiac function occurred in 7.8% of the patients. Advanced age, NYHA class, high blood urea nitrogen, hypoalbuminemia, and vasopressor use were its strongest predictors. The prediction model showed good discrimination C-statistic value, 0.866 (95% CI, 0.817–0.907), which indicated good identical calibration and clinical efficacy.Conclusion: In this study, we developed a prediction model and nomogram to estimate the risk of irreversible worsening of cardiac function among ADHF patients. The findings may provide a reference for clinical physicians for detection of irreversible worsening of cardiac function and enable its prompt management.

Abstract P328: Angiotensin II Inhibits the High Salt-induced Production of Sphigosine-1-phosphate in the Renal Medulla

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Weili Wang ◽  
Junping Hu ◽  
Pin-Lan Li ◽  
Justin L Poklis ◽  
Ningjun Li
Keyword(s):  
Angiotensin Ii ◽  
Renal Medulla ◽  
High Salt ◽  
Ang Ii ◽  
Male Adult ◽  
High Salt Diet ◽  
Salt Diet ◽  
Protein Levels ◽  
Medullary Tissue ◽  
Natriuretic Effect

We have previously shown that sphigosine-1-phosphate (S1P) produces natriuretic effects via activation of S1P receptor 1 in the renal medulla and that this natriuretic effect may be through inhibition of epithelial sodium channel. The present study examined the expression of the enzymes that produce S1P in the renal medullary tissue and tested the hypothesis that angiotensin II (ANG II) reduces the expression of S1P-producing enzyme and thereby the levels of S1P in the renal medulla. Male adult C56BL/6 mice, 10-12 weeks old, were treated with a low salt diet (LS, 0.4%), high salt diet (HS, 4% NaCl) or HS + ANG II (600ng/kg/min, S.C.) for 10 days. A high salt diet increased the level of S1P, whereas ANG II significantly inhibited the HS-induced increase of S1P levels in the renal medullary tissue. The levels of S1P were 6.6 ± 0.34, 11.4 ± 1.33 and 3.5 ± 0.49 pmol/mg of tissue in LS, HS and HS + ANG II group, respectively. There were no difference in the levels of sphingosine kinase 1 (SPHK1), the enzyme that produces S1P by phosphorylating sphingosine, among the different groups of mice by Western blot analysis. However, a high salt diet increased the protein levels of acid ceramidase (ACDase), an upstream enzyme that produces sphingosine, the substrate for SPHK1. This HS-induced increase in ACDase was inhibited by ANG II. The relative protein levels of ACDase were 1.0 ± 0.07, 1.4 ± 0.07 and 0.17 ± 0.11 in LS, HS and HS + ANG II group, respectively. These results demonstrated that a high salt diet increased the levels of S1P in the renal medulla, probably by increasing the level of one of the S1P-producing enzymes ACDase, and that ANG II reduced the levels of ACDase and S1P in the renal medulla. Given the diuretic effect of S1P, ANG II-induced reduction of S1P production in the renal medulla may be a mechanism contributing to the sodium retention and hypertension associated with excessive ANG II. (Support: NIH grant HL89563)

scholarly journals The power of optimal medical therapy using angiotensin receptor-neprilysin inhibitor in acute decompensated heart failure, sparing a critical patient open-heart surgery with a device therapy: a case report

2020 ◽  
Author(s):  
Fady Gerges ◽  
Austin Komaranchath ◽  
Faiz Al Bakshy ◽  
Abdallah Almaghraby
Keyword(s):  
Heart Failure ◽  
Case Report ◽  
Coronary Artery ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract Background Timely use of Sacubitril/Valsartan has the potential to significantly improve cardiac function and dramatically reduce secondary mitral regurgitation (MR) severity even in patients presenting with acute decompensated heart failure (HF), not only in compensated chronic HF patients. The outstanding impact of echocardiography is obvious in monitoring improvement of cardiac function and MR severity in patients with HF with reduced ejection fraction (HFrEF). Case summary We report a relevant case of an elderly patient who presented with acute decompensated HF and severe MR. He was symptomatic despite being on maximally tolerated doses of ACEI, beta-blockers, and diuretics. Left ventricular ejection fraction (LVEF) improved from 15% to 35% 2 weeks following initiation of Sacubitril/Valsartan during second HF hospitalization. There was a dramatic improvement of patient’s symptoms from New York Heart Association (NYHA) Class IV to NYHA I. N-terminal pro B-type natriuretic peptide reduced from 9000 pg/mL to 800 pg/mL. Coronary angiography depicted three-vessel coronary artery disease. The patient was advised to undergo coronary artery bypass graft surgery with mitral valve repair, then followed by implantation of a cardiac resynchronization therapy-defibrillator device (CRT-D) if no LV function improvement is observed after revascularization. The electrocardiogram showed Q waves in inferior leads with QRSd ≥ 125 ms, hence a good candidate for CRT. Following an elective percutaneous coronary intervention, LVEF further improved to 50%. The patient became asymptomatic with preserved LVEF on follow-up for 18 months later. Discussion This case report documents the swift echocardiographic and symptom improvement in a decompensated end-stage HF patient when Sacubitril/Valsartan initiated during acute setting.

scholarly journals Temporal changes of cardiac acoustic biomarkers and cardiac function in acute decompensated heart failure

2021 ◽  
Author(s):  
Jun Shitara ◽  
Takatoshi Kasai ◽  
Nobutaka Murata ◽  
Nobuhide Yamakawa ◽  
Shoichiro Yatsu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Temporal Changes

scholarly journals BALB/cJBom Treated with Angiotensin II and High Salt Diet Develop Pulmonary Hypertension and Right Sided Heart Failure while C57BL/6J Mice do not

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Mediha Becirovic‐Agic ◽  
Sofia Jönsson ◽  
Maria K. Tveitarås ◽  
Trude Skogstrand ◽  
Tine V. Karlsen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Angiotensin Ii ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet

scholarly journals Addition of a β1-Blocker to Milrinone Treatment Improves Cardiac Function in Patients with Acute Heart Failure and Rapid Atrial Fibrillation

Cardiology ◽  
2019 ◽  
Vol 142 (4) ◽  
pp. 195-202
Author(s):  
Shigeki Kobayashi ◽  
Takeki Myoren ◽  
Toshiro Kajii ◽  
Michiaki Kohno ◽  
Takuma Nanno ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
New York ◽  
Cardiac Function ◽  
Acute Decompensated Heart Failure ◽  
Stroke Volume Index ◽  
Heart Association ◽  
Decompensated Heart Failure ◽  
Left Ventricular ◽  
Volume Index

Background: Tachycardia worsens cardiac performance in acute decompensated heart failure (ADHF). We investigated whether heart rate (HR) optimization by landiolol, an ultra-short-acting β1-selective blocker, in combination with milrinone improved cardiac function in patients with ADHF and rapid atrial fibrillation (AF). Methods and Results: We enrolled9 ADHF patients (New York Heart Association classification IV; HR, 138 ± 18 bpm; left ventricular [LV] ejection fraction, 28 ± 8%; cardiac index [CI], 2.1 ± 0.3 L/min–1/m–2; pulmonary capillary wedge pressure [PCWP], 24 ± 3 mm Hg), whose HRs could not be reduced using standard treatments, including diuretics, vasodilators, and milrinone. Landiolol (1.5–6.0 µg/kg–1/min–1, intravenous) was added to milrinone treatment to study its effect on hemodynamics. The addition of landiolol (1.5 µg/kg–1/min–1) significantly reduced HR by 11% without changing systolic blood pressure (BP) and resulted in a significant decrease in PCWP and a significant increase in stroke volume index (SVI), suggesting that HR reduction restores incomplete LV relaxation. Administration of more than 3.0 µg/kg–1/min–1 of landiolol decreased BP, CI, and SVI. Conclusion: The addition of landiolol at doses of <3.0 µg/kg/min to milrinone improved cardiac function in decompensated chronic heart failure with rapid atrial fibrillation by selectively reducing HR.

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