Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure

2007 ◽  
Vol 29 (3) ◽  
pp. 246-252 ◽  
Author(s):  
Natale P. L. Rolim ◽  
Alessandra Medeiros ◽  
Kaleizu T. Rosa ◽  
Katt C. Mattos ◽  
Maria C. Irigoyen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Cardiac Myocyte ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Exercise Intolerance ◽  
Computer Assisted ◽  
Wild Type ◽  
Beneficial Effects ◽  
Ventricular Fibrosis

The molecular basis of the beneficial effects associated with exercise training (ET) on overall ventricular function (VF) in heart failure (HF) remains unclear. We investigated potential Ca2+ handling abnormalities and whether ET would improve VF of mice lacking α2A- and α2C-adrenoceptors (α2A/α2CARKO) that have sympathetic hyperactivity-induced HF. A cohort of male wild-type (WT) and congenic α2A/α2CARKO mice in a C57BL/J genetic background (5–7 mo of age) was randomly assigned into untrained and trained groups. VF was assessed by two-dimensional guided M-mode echocardiography. Cardiac myocyte width and ventricular fibrosis were evaluated with a computer-assisted morphometric system. Sarcoplasmic reticulum Ca2+ ATPase (SERCA2), phospholamban (PLN), phospho-Ser16-PLN, phospho-Thr17-PLN, phosphatase 1 (PP1), and Na+-Ca2+ exchanger (NCX) were analyzed by Western blotting. ET consisted of 8-wk running sessions of 60 min, 5 days/wk. α2A/α2CARKO mice displayed exercise intolerance, systolic dysfunction, increased cardiac myocyte width, and ventricular fibrosis paralleled by decreased SERCA2 and increased NCX expression levels. ET in α2A/α2CARKO mice improved exercise tolerance and systolic function. ET slightly reduced cardiac myocyte width, but unchanged ventricular fibrosis in α2A/α2CARKO mice. ET significantly increased the expression of SERCA2 (20%) and phospho-Ser16-PLN (63%), phospho-Thr17-PLN (211%) in α2A/α2CARKO mice. Furthermore, ET restored NCX and PP1 expression in α2A/α2CARKO to untrained WT mice levels. Thus, we provide evidence that Ca2+ handling is impaired in this HF model and that overall VF improved upon ET, which was associated to changes in the net balance of cardiac Ca2+ handling proteins.

scholarly journals Effects of exercise training on neurovascular control and skeletal myopathy in systolic heart failure

2015 ◽  
Vol 308 (8) ◽  
pp. H792-H802 ◽  
Author(s):  
Carlos E. Negrao ◽  
Holly R. Middlekauff ◽  
Igor L. Gomes-Santos ◽  
Ligia M. Antunes-Correa
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Systolic Dysfunction ◽  
Systolic Heart Failure ◽  
Exercise Intolerance ◽  
Peripheral Blood Flow ◽  
Peripheral Vasoconstriction ◽  
Beneficial Effects ◽  
Ventilatory Responses ◽  
Skeletal Myopathy

Neurohormonal excitation and dyspnea are the hallmarks of heart failure (HF) and have long been associated with poor prognosis in HF patients. Sympathetic nerve activity (SNA) and ventilatory equivalent of carbon dioxide (VE/VO2) are elevated in moderate HF patients and increased even further in severe HF patients. The increase in SNA in HF patients is present regardless of age, sex, and etiology of systolic dysfunction. Neurohormonal activation is the major mediator of the peripheral vasoconstriction characteristic of HF patients. In addition, reduction in peripheral blood flow increases muscle inflammation, oxidative stress, and protein degradation, which is the essence of the skeletal myopathy and exercise intolerance in HF. Here we discuss the beneficial effects of exercise training on resting SNA in patients with systolic HF and its central and peripheral mechanisms of control. Furthermore, we discuss the exercise-mediated improvement in peripheral vasoconstriction in patients with HF. We will also focus on the effects of exercise training on ventilatory responses. Finally, we review the effects of exercise training on features of the skeletal myopathy in HF. In summary, exercise training plays an important role in HF, working synergistically with pharmacological therapies to ameliorate these abnormalities in clinical practice.

Abstract 71: STAT3 Affects Myofibrillar Structure and Its Loss May Contribute to Heart Failure in Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Fouad Zouein ◽  
Carlos Zgheib ◽  
John Fuseler ◽  
John E Hall ◽  
Mazen Kurdi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Myocytes ◽  
Transcriptional Activity ◽  
Cardiac Myocyte ◽  
Early Stage ◽  
Systolic Dysfunction ◽  
Wild Type ◽  
Patients With Heart Failure ◽  
Protective Proteins ◽  
Fractional Shortening

How hypertension causes heart failure is not known. Since patients with heart failure have reduced cardiac STAT3 and STAT3 KO mice develop heart failure with age, we tested the hypothesis that reduced STAT3 transcriptional activity contributes at an early stage to remodeling that precedes heart failure in hypertension using SA mice with a STAT3 S727A mutation. SA and wild type (WT) mice received angiotensin (A) II (1000 ng/kg/min) or saline (S) for 17 days. Hearts of WT and SA mice had similar levels of STAT3-induced protective proteins Bcl-xL and SOD2, and unlike STAT3 KO mice, cardiac miR-199a levels were not increased in SA mice. AII increased systolic blood pressure measured by telemetry in SA (124 ± 1 to 167 ± 3) and WT (122 ± 3 to 162 ± 3) mice to the same extent. AII increased cardiac levels of cytokines (pg/μg protein) associated with heart failure in both WT and SA mice, but significantly less so (P<0.05) in SA mice; IL-6, 13.6 ± 1.4 vs. 9.1 ± 0.6; TGFβ, 56 ± 4 vs. 38 ± 3 and MCP1 35 ± 2 vs. 22 ± 2. Compared to WT mice, hearts of SA mice showed signs of developing systolic dysfunction with AII as seen by a significant (P<0.05) reduction in ejection fraction (63.7 ± 7.1 to 51.7 ± 6.9) and fractional shortening (34.3 ± 4.9 to 26.4 ± 4.3). AII caused fibrosis in the left ventricle of both WT and SA mice characterized by cardiac myocyte loss and increased % collagen: WT+S, 5.59 ± 0.34; WT+AII, 15.70 ± 1.87; SA+S, 6.70 ± 0.40; SA+AII, 16.50 ± 1.91. In WT+AII mice there was a nonsignificant trend towards a loss of myofibrillar content of cardiac myocytes, but an increase in the mass of the myofibrils (IOD/myofibrillar area). In contrast, cardiac myocytes of SA+AII mice had a significant (P<0.001) % loss in myofibrils (5.71 ± 0.28) compared to SA+S (0.75 ± 0.07), WT+S (0.80 ± 0.06) and WT+AII (1.54 ± 0.10) mice. In addition, the mass of the myofibrils in SA+AII mice (6.01 ± 0.07) was significantly less (P<0.001) than those of SA+S mice (6.46 ± 0.04), although greater than WT+S (4.85 ± 0.06) or WT+AII (5.27 ± 0.08) mice. Our findings reveal that STAT3 transcriptional activity is important for proper morphology of the myofibrils of cardiac myocytes. Loss of STAT3 activity may impair cardiac function in the hypertensive heart due to defective myofibrillar structure and remodeling that may lead to heart failure.

scholarly journals Exercise Training for Heart Failure Patients with and without Systolic Dysfunction: An Evidence-Based Analysis of How Patients Benefit

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Neil Smart
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Systolic Function ◽  
Controlled Trial ◽  
Systolic Dysfunction ◽  
Systolic Heart Failure ◽  
Evidence Based ◽  
Heart Failure Patients ◽  
Age Related ◽  
Clinical Benefits

Significant benefits can be derived by heart failure patients from exercise training. This paper provides an evidence-based assessment of expected clinical benefits of exercise training for heart failure patients. Meta-analyses and randomized, controlled trials of exercise training in heart failure patients were reviewed from a search of PubMed, Cochrane Controlled Trial Registry (CCTR), CINAHL, and EMBASE. Exercise training improves functional capacity, quality of life, hospitalization, and systolic and diastolic function in heart failure patients. Heart failure patients with preserved systolic function (HFnEF) participating in exercise training studies are more likely to be women and are 5–7 years older than their systolic heart failure (CHF) counterparts. All patients exhibit low functional capacities, although in HFnEF patients this may be age related, therefore subtle differences in exercise prescriptions are required. Published works report that exercise training is beneficial for heart failure patients with and without systolic dysfunction.

scholarly journals Central and obstructive apneas prevalence in heart failure with reduced, mid-range and preserved ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Borrelli ◽  
P Sciarrone ◽  
F Gentile ◽  
N Ghionzoli ◽  
G Mirizzi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Cardiopulmonary Exercise Testing ◽  
Left Ventricular ◽  
Apnea Hypopnea Index ◽  
Preserved Ejection Fraction ◽  
2D Echocardiography

Abstract Background Central apneas (CA) and obstructive apneas (OA) are highly prevalent in heart failure (HF) both with reduced and preserved systolic function. However, a comprehensive evaluation of apnea prevalence across HF according to ejection fraction (i.e HF with patients with reduced, mid-range and preserved ejection fraction- HFrEf, HFmrEF and HFpEF, respectively) throughout the 24 hours has never been done before. Materials and methods 700 HF patients were prospectively enrolled and then divided according to left ventricular EF (408 HFrEF, 117 HFmrEF, 175 HFpEF). All patients underwent a thorough evaluation including: 2D echocardiography; 24-h Holter-ECG monitoring; cardiopulmonary exercise testing; neuro-hormonal assessment and 24-h cardiorespiratory monitoring. Results In the whole population, prevalence of normal breathing (NB), CA and OA at daytime was 40%, 51%, and 9%, respectively, while at nighttime 15%, 55%, and 30%, respectively. When stratified according to left ventricular EF, CA prevalence decreased from HFrEF to HFmrEF and HFpEF: (daytime CA: 57% vs. 43% vs. 42%, respectively, p=0.001; nighttime CA: 66% vs. 48% vs. 34%, respectively, p&lt;0.0001), while OA prevalence increased (daytime OA: 5% vs. 8% vs. 18%, respectively, p&lt;0.0001; nighttime OA: 20 vs. 29 vs. 53%, respectively, p&lt;0.0001). When assessing moderte-severe apneas, defined with an apnea/hypopnea index &gt;15 events/hour, prevalence of CA was again higher in HFrEF than HFmrEF and HFpEF both at daytime (daytime moderate-severe CA: 28% vs. 19% and 23%, respectively, p&lt;0.05) and at nighttime (nighttime moderate-severe CA: 50% vs. 39% and 28%, respectively, p&lt;0.05). Conversely, moderate-severe OA decreased from HFrEF to HFmrEF to HFpEF both at daytime (daytime moderate-severe OA: 1% vs. 3% and 8%, respectively, p&lt;0.05) and nighttime (noghttime moderate-severe OA: 10% vs. 11% and 30%, respectively, p&lt;0.05). Conclusions Daytime and nighttime apneas, both central and obstructive in nature, are highly prevalent in HF regardless of EF. Across the whole spectrum of HF, CA prevalence increases and OA decreases as left ventricular systolic dysfunction progresses, both during daytime and nighttime. Funding Acknowledgement Type of funding source: None

scholarly journals Exercise training normalizes elevated firing rate of hypothalamic presympathetic neurons in heart failure rats

2019 ◽  
Vol 316 (2) ◽  
pp. R110-R120 ◽  
Author(s):  
Yiming Shen ◽  
Jin Bong Park ◽  
So Yeong Lee ◽  
Seong Kyu Han ◽  
Pan Dong Ryu
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Firing Rate ◽  
Gaba Release ◽  
Neuronal Firing ◽  
Ventrolateral Medulla ◽  
Patch Clamp Technique ◽  
Electrophysiological Properties ◽  
Beneficial Effects ◽  
Underlying Mechanisms

Exercise training (ExT) normalizes elevated sympathetic nerve activity in heart failure (HF), but the underlying mechanisms are not well understood. In this study, we examined the effects of 3 wk of ExT on the electrical activity of the hypothalamic presympathetic neurons in the brain slice of HF rats. HF rats were prepared by ligating the left descending coronary artery. The electrophysiological properties of paraventricular nucleus neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) were examined using the slice patch-clamp technique. The neuronal firing rate was elevated in HF rats, and ExT induced a reduction in the firing rate ( P < 0.01). This ExT-induced decrease in the firing rate was associated with an increased frequency of spontaneous and miniature inhibitory postsynaptic current (IPSCs; P < 0.05). There was no significant change in excitatory postsynaptic current. Replacing Ca2+ with Mg2+ in the recording solution reduced the elevated IPSC frequency in HF rats with ExT ( P < 0.01) but not in those without ExT, indicating an increase in the probability of GABA release. In contrast, ExT did not restore the reduced GABAA receptor-mediated tonic inhibitory current in HF rats. A GABAA receptor blocker (bicuculline, 20 μM) increased the firing rate in HF rats with ExT ( P < 0.01) but not in those without ExT. Collectively, these results show that ExT normalized the elevated firing activity by increasing synaptic GABA release in PVN-RVLM neurons in HF rats. Our findings provide a brain mechanism underlying the beneficial effects of ExT in HF, which may shed light on the pathophysiology of other diseases accompanied by sympathetic hyperactivation.

Unraveling new mechanisms of exercise intolerance in chronic heart failure. Role of exercise training

2012 ◽  
Vol 18 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Viviane M. Conraads ◽  
Emeline M. Van Craenenbroeck ◽  
Catherine De Maeyer ◽  
An M. Van Berendoncks ◽  
Paul J. Beckers ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Exercise Intolerance

Plasma cardiotrophin-1 following acute myocardial infarction: relationship with left ventricular systolic dysfunction

2001 ◽  
Vol 102 (1) ◽  
pp. 9-14 ◽  
Author(s):  
Suneel TALWAR ◽  
Iain B. SQUIRE ◽  
Russell J. O'BRIEN ◽  
Paul F. DOWNIE ◽  
Joan E. DAVIES ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Clinic Visit ◽  
Left Ventricular ◽  
Lv Function ◽  
Ventricular Remodelling

The glycoprotein 130 (gp130) signalling pathway is important in the development of heart failure. Cardiotrophin-1 (CT-1), a cytokine acting via the gp130 pathway, is involved in the process of ventricular remodelling following acute myocardial infarction (AMI) in animals. The aims of the present study were to examine the profile of plasma CT-1 following AMI in humans, and its relationship with echocardiographic parameters of left ventricular (LV) systolic function. Serial measurements of plasma CT-1 levels were made in 60 patients at 14-48h, 49-72h, 73-120h and 121-192h following AMI and at a later clinic visit. LV function was assessed using a LV wall motion index (WMI) score on admission (WMI-1) and at the clinic visit (WMI-2). Compared with values in control subjects (29.5±3.6fmol/ml), the plasma CT-1 concentration was elevated in AMI patients at 14-48h (108.1±15.1fmol/ml), 49-72h (105.2±19.7fmol/ml), 73-120h (91.2±14.9fmol/ml) and 121-192h (118.8±22.6fmol/ml), and at the clinic visit (174.9±30.9 fmol/ml) (P < 0.0001). Levels were higher following anterior compared with inferior AMI. For patients with anterior AMI, CT-1 levels were higher at the clinic visit than at earlier times. WMI-1 correlated with CT-1 at all times prior to hospital discharge (P < 0.05). On best subsets analysis, the strongest correlate with WMI-1 was CT-1 level at 49-72h (R2 = 20%, P < 0.05). In conclusion, plasma levels of CT-1 are elevated soon after AMI in humans and rise further in the subsequent weeks in patients after anterior infarction. CT-1 measured soon after AMI is indicative of LV dysfunction, and this cytokine may have a role in the development of ventricular remodelling and heart failure after AMI.

2371Electrocardiographic features and their echocardiographic correlates in peripartum cardiomyopathy based on the EURObservational registry on PPCM

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A C Mbakwem ◽  
J Bauersachs ◽  
C Viljoen ◽  
P Van Der Meer ◽  
M Petrie ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ethnic Differences ◽  
Regional Differences ◽  
Sinus Tachycardia ◽  
Systolic Function ◽  
Nyha Class ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Peripartum Cardiomyopathy ◽  
Qtc Interval

Abstract Background Cardiac disease remains an important cause of maternal morbidity and mortality globally. Peripartum cardiomyopathy (PPCM), defined as heart failure secondary to left ventricular (LV) systolic dysfunction in previously healthy women towards the end of pregnancy or up to five months following delivery, can result in cardiogenic shock due to severe LV dysfunction or arrhythmias leading to sudden cardiac death. Cardiac electrical activity and its relationship to cardiac dysfunction have not yet been interrogated in large multi-centre studies. Purpose This study aimed to identify the ECG abnormalities associated with PPCM; their relationship with echocardiographic structural and functional abnormalities and explore regional and ethnic differences in ECG features. Methods We included the first 411 patients enrolled into the EURObservational PPCM registry (EORP). Baseline demographic, clinical and echocardiographic data were collected. ECGs were analysed for rate; rhythm; QRS width, axis and morphology; and QTc interval. Results Mean age of the women (from >40 countries) was 30.7±6.4 years. More than two thirds of patients presented with NYHA class III or IV (with no regional differences). The median QRS rate was 102bpm (IQR 87–117). More than half presented with sinus tachycardia (QRS rate >100bpm), whereas atrial fibrillation was rare (2.27%). The mean QRS width was 90.1ms ±21.5, with regional differences (ESC 93.8ms ±21.7 vs. non-ESC 86.8ms ±20.8, P<0.001). Left bundle branch block (LBBB) was reported in 9.30% with no regional or ethnic differences. Left ventricular hypertrophy (LVH) was present in a quarter of the cohort, and more prevalent amongst African (59.62%) and Asian (23.17%) than Caucasians (7.63%, P<0.001). The median QTc by Bazett was 456.7ms (IQR 409–490.7) and almost half (47.11%) had prolonged QTc (>460ms). The median LVEDD was 60mm (IQR 55–65) on echocardiography. Compared with their Asian and Caucasian counterparts, African patients were more likely to have LV dilatation (LVEDD>53mm: 70.11%, 79.31% and 89.42% respectively; P=0.004). The median LV ejection fraction (LVEF) was 32.50% (IQR 25–39) with no significant regional or ethnic differences. Sinus tachycardia predicted poor systolic function (OR 1.85 [95% CI 1.20–2.85], p=0.006). LVEF <35% was associated with a significantly higher QRS rate (median rate 107 vs. 98bpm, p=0.002). Women with LVEDD ≥53mm had a longer mean QRS duration (92.0±22.4 vs. 82.4±15.4ms, p<0.001) and frequency of LBBB (11.15% vs 1.54%, p=0.016). LBBB was a predictor of LVEDD >53mm (sensitivity 11.15%; specificity 98.46%; PPV 97.14%; NPV 19.10%; OR 8.02 [95% CI 1.08–59.66], p=0.042). Conclusion Patients with PPCM commonly present with sinus tachycardia, LVH, and/or prolonged QTc interval on their ECG. Wide QRS and/or LBBB, were associated with LVEDD>53mm. Sinus tachycardia, however, was associated with LVEF<35%. Risk of arrhythmia in those with prolonged QTc remains to be ascertained. Acknowledgement/Funding Heart Failure Association of the ESC

scholarly journals The heart regulates the endocrine response to heart failure: cardiac contribution to circulating neprilysin

2017 ◽  
Vol 39 (20) ◽  
pp. 1794-1798 ◽  
Author(s):  
Mattia Arrigo ◽  
Nicolas Vodovar ◽  
Hélène Nougué ◽  
Malha Sadoune ◽  
Chris J Pemberton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Sinus ◽  
Artificial Heart ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Venous Blood ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Total Artificial Heart ◽  
Endocrine Response

Abstract Aims Heart failure (HF) is accompanied by major neuroendocrine changes including the activation of the natriuretic peptide (NP) pathway. Using the unique model of patients undergoing implantation of the CARMAT total artificial heart and investigating regional differences in soluble neprilysin (sNEP) in patients with reduced or preserved systolic function, we studied the regulation of the NP pathway in HF. Methods and results Venous blood samples from two patients undergoing replacement of the failing ventricles with a total artificial heart were collected before implantation and weekly thereafter until post-operative week 6. The ventricular removal was associated with an immediate drop in circulating NPs, a nearly total disappearance of circulating glycosylated proBNP and furin activity and a marked decrease in sNEP. From post-operative week 1 onwards, NP concentrations remained overall unchanged. In contrast, partial recoveries in glycosylated proBNP, furin activity, and sNEP were observed. Furthermore, while in patients with preserved systolic function (n = 6), sNEP concentrations in the coronary sinus and systemic vessels were similar (all P > 0.05), in patients with reduced left-ventricular systolic function, sNEP concentration, and activity were ∼three-fold higher in coronary sinus compared to systemic vessels (n = 21, all P < 0.0001), while the trans-pulmonary gradient was neutral (n = 5, P = 1.0). Conclusion The heart plays a pivotal role as a regulator of the endocrine response in systolic dysfunction, not only by directly releasing NPs but also by contributing to circulating sNEP, which in turn determines the bioavailability of other numerous vasoactive peptides.

scholarly journals Clinical Utility of Exercise Training in Heart Failure with Reduced and Preserved Ejection Fraction

2015 ◽  
Vol 9 ◽  
pp. CMC.S21372 ◽  
Author(s):  
Muhammad Asrar Ul Haq ◽  
Cheng Yee Goh ◽  
Itamar Levinger ◽  
Chiew Wong ◽  
David L. Hare
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Ejection Fraction ◽  
Exercise Tolerance ◽  
Exercise Intolerance ◽  
Sufficient Evidence ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure

Reduced exercise tolerance is an independent predictor of hospital readmission and mortality in patients with heart failure (HF). Exercise training for HF patients is well established as an adjunct therapy, and there is sufficient evidence to support the favorable role of exercise training programs for HF patients over and above the optimal medical therapy. Some of the documented benefits include improved functional capacity, quality of life (QoL), fatigue, and dyspnea. Major trials to assess exercise training in HF have, however, focused on heart failure with reduced ejection fraction (HFREF). At least half of the patients presenting with HF have heart failure with preserved ejection fraction (HFPEF) and experience similar symptoms of exercise intolerance, dyspnea, and early fatigue, and similar mortality risk and rehospitalization rates. The role of exercise training in the management of HFPEF remains less clear. This article provides a brief overview of pathophysiology of reduced exercise tolerance in HFREF and heart failure with preserved ejection fraction (HFPEF), and summarizes the evidence and mechanisms by which exercise training can improve symptoms and HF. Clinical and practical aspects of exercise training prescription are also discussed.

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