Abstract 1509: Exercise Training Started Before Myocardial Infarction Improves Survival but Aggravates Left Ventricular Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monique C de Waard ◽  
Dirk J Duncker
Keyword(s):  
Myocardial Infarction ◽  
Exercise Training ◽  
Wheel Running ◽  
Left Ventricular ◽  
Lv Function ◽  
Cardiac Events ◽  
Cross Sectional ◽  
Voluntary Wheel Running ◽  
Lv Dysfunction ◽  
Voluntary Wheel

Introduction: Regular physical activity in patients with established coronary heart disease not only reduces the incidence of cardiac events, but also reduces the risk of all-cause mortality. Recently, we showed in mice that exercise training (EX) started immediately after myocardial infarction (MI) ameliorates left ventricular (LV) dysfunction. Here we tested the hypothesis that additional exercise training prior to an acute MI, i.e. a higher level of physical fitness at the time of MI, is associated with improved survival and attenuated LV dysfunction after MI. Methods and Results: MI was induced by permanent coronary ligation in 128 C57Bl/6 mice and subsequently followed by 8 weeks of voluntary wheel running (MI-EX) or sedentary housing (MI). In a third group, voluntary wheel running was started two weeks before induction of MI (EX-MI-EX). Sham operated mice served as controls. EX after MI had no effect on survival, infarct size, LV hypertrophy or dilation (Table ). However, EX improved LV function, reflected in enhanced LV fractional shortening (FS), rate of rise in LV pressure at 30 mmHg (LVdP/dt P30 ), and decreased pulmonary congestion and right ventricular weight (RVW). When EX was started prior to MI, post-MI survival nearly doubled and mice ran an average post-MI distance of ~7km/d compared to ~5km/d in MI-EX mice. Infarct cross-sectional area was larger, which was principally due to an increased infarct thickness (0.15±0.02mm EX-MI-EX vs 0.11±0.01mm MI; P =0.06). Surprisingly, however, LV hypertrophy and dysfunction were aggravated in the EX-MI-EX group compared to MI-EX. Conclusion: In line with our hypothesis, EX started prior to MI improved survival. However, contrary to our hypothesis, the improved survival was associated with a deterioration of LV dysfunction. The latter may have been the result of survival and hence inclusion of mice with the most severe LV dysfunction.

Abstract 14119: Contrasting Effects of Exercise Training After Acute Myocardial Infarction versus Aortic Stenosis Depend Critically on the Regulation of Endothelial Nitric Oxide Synthase

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yanti Octavia ◽  
Elza D van Deel ◽  
Monique de Waard ◽  
Martine de Boer ◽  
Dirk J Duncker
Keyword(s):  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Exercise Training ◽  
Wheel Running ◽  
Left Ventricular ◽  
Lv Function ◽  
Enhanced Chemiluminescence ◽  
Lv Dysfunction ◽  
Enos Uncoupling ◽  
Endothelial Nitric Oxide

Introduction: The cardiovascular benefits of exercise training (EX) are widely appreciated. Previously we found that the cardiac effects of EX critically depend on the underlying cause of heart disease. Hypothesis: The underlying etiology determines how EX affects the endothelial nitric oxide (NO) synthase (eNOS)-mediated balance between NO and superoxide (O2-). Methods: Mice were subjected to sham surgery, myocardial infarction (MI) or transverse aortic constriction (TAC), and subsequently exposed to 8 weeks of voluntary wheel running or sedentary housing. Left ventricular (LV) function was assessed by echocardiography and hemodynamic measurements; fibrosis by Picro-sirius Red staining; peroxynitrite (ONOO-) and O2- production by luminol- and lucigenin-enhanced chemiluminescence respectively, with or without the NOS inhibitor L-NAME; eNOS uncoupling and eNOS S-glutathionylation by western blot and coimmunoprecipitation, respectively; cardiac NO by the Griess reaction. Results: EX ameliorated LV dysfunction and fibrosis in MI but not TAC (Table 1). Strikingly, O2- generation was blunted by EX in MI, but exacerbated by EX in TAC, which was largely NOS-dependent. Accordingly, eNOS uncoupling and eNOS S-glutathionylation were corrected by EX in MI but aggravated in TAC mice. In parallel, ONOO- levels was attenuated by EX in MI but aggravated by EX in TAC. Cardiac NO levels were reduced in MI and TAC and normalized by EX in MI. Conclusions: The contrasting effects of EX in MI vs TAC can be explained by the highly divergent effects of EX on eNOS regulation, resulting in blunted vs aggravated oxidative stress by EX in MI vs TAC.

Prior exercise improves survival, infarct healing, and left ventricular function after myocardial infarction

2009 ◽  
Vol 107 (3) ◽  
pp. 928-936 ◽  
Author(s):  
Monique C. de Waard ◽  
Dirk J. Duncker
Keyword(s):  
Myocardial Infarction ◽  
Exercise Intervention ◽  
Wheel Running ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Voluntary Wheel Running ◽  
Lv Dysfunction ◽  
Lv Remodeling ◽  
Before And After ◽  
Voluntary Wheel

We investigated the effects of voluntary wheel running before an acute myocardial infarction (MI) on survival, left ventricular (LV) remodeling and dysfunction and whether exercise before and after MI provides superior protection compared with either exercise intervention alone. After 2 wk of voluntary wheel running or sedentary housing, MI was induced in C57Bl/6 mice, after which exercise was stopped (EX-MI-SED and SED-MI-SED groups, where EX is exercise and SED is sedentary) or continued (EX-MI-EX and SED-MI-EX groups) for a period of 8 wk. Exercise after MI in SED-MI-EX mice had no effect on survival, the area of infarction, and global LV remodeling, but attenuated fibrosis and apoptosis in the remote myocardium and blunted LV dysfunction and pulmonary congestion compared with SED-MI-SED mice. Exercise before MI in both EX-MI-SED and EX-MI-EX mice decreased post-MI mortality compared with both SED-MI-SED and SED-MI-EX mice. Furthermore, in both pre-MI exercise groups, the infarct area was thicker, whereas interstitial fibrosis and apoptosis in the remote LV myocardium were blunted. In contrast, the ameliorating effects of either pre-MI or post-MI exercise alone on LV dysfunction were lost in EX-MI-EX mice, which may in part be related to the increased daily exercise distance in the first week post-MI in EX-MI-EX versus SED-MI-EX mice. In conclusion, exercise before or after MI blunted LV dysfunction, whereas only exercise before MI improved survival. These findings suggest that even when regular physical activity fails to prevent an acute MI, it can still act to improve cardiac function and survival after MI.

scholarly journals Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial

Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001614
Author(s):  
Mohammad R Ostovaneh ◽  
Raj R Makkar ◽  
Bharath Ambale-Venkatesh ◽  
Deborah Ascheim ◽  
Tarun Chakravarty ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Clinical Trial ◽  
Myocardial Function ◽  
Randomised Clinical Trial ◽  
Scar Tissue ◽  
Left Ventricular ◽  
Lv Function ◽  
Cardiac Events ◽  
Lv Dysfunction ◽  
Registration Number

BackgroundMost cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.MethodsIn this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups.ResultsIn total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (−0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of −0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04).ConclusionsIn patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI.Trial registration numberNCT01458405.

scholarly journals Comparison of changes in electrical activity, in isolated and in vivo hearts, induced by voluntary exercise in female rats

2020 ◽  
Author(s):  
Rachel Stones ◽  
Mark Drinkhill ◽  
Ed White
Keyword(s):  
Exercise Training ◽  
Electrical Activity ◽  
Wheel Running ◽  
Left Ventricular ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Heart Weight ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

AbstractRegular mild exercise is recommended to the general population as beneficial to health. Regular exercise typically leads to structural and electrical remodelling of the heart but in human studies it is difficult to relate the extrinsic and intrinsic influences on intact hearts to changes seen at the single cell level. In this study we wished to test whether changes in electrical activity in intact hearts, in response to voluntary wheel running exercise training, were consistent with our previous observations in single cardiac myocytes and whether these changes resulted in altered susceptibility to arrhythmic stimuli.Female rats performed 5 weeks of voluntary wheel running. Implanted telemetry transmitters were used to measure electrocardiograms (ECGs) and determine heart rate variability (HRV) in conscious, unrestrained, trained (TRN) and sedentary (SED) animals. In isolated hearts, left ventricular epicardial monophasic action potentials (MAPs) were recorded and the responses to potentially arrhythmic interventions were assessed.Exercise training caused cardiac hypertrophy, as indexed by a significantly greater heart weight to body weight ratio. Consistent with previous measurements of action potential duration in single myocytes, MAPs were significantly longer at 50%, 75% and 90% repolarization. Arrhythmic susceptibility was not different between SED and TRN hearts. Trained animals displayed significantly altered HRV by week 5, in a manner consistent with reduced sympathetic tone, however resting ECG parameters, including those most associated with repolarisation duration, were unaltered. We conclude that intrinsic changes to cellular cardiac electrophysiology, induced by mild voluntary exercise, are not attenuated by the electronic loading that occurs in intact hearts. However, in vivo, extrinsic neuro-hormonal control of the heart may minimize the effects of intrinsic alterations in electrical activity.

Regulation of components of the brain and cardiac renin-angiotensin systems by 17β-estradiol after myocardial infarction in female rats

2006 ◽  
Vol 291 (1) ◽  
pp. R155-R162 ◽  
Author(s):  
Stephanie A. Dean ◽  
Junhui Tan ◽  
Roselyn White ◽  
Edward R. O’Brien ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular ◽  
Female Rats ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Brain Nuclei ◽  
Renin Angiotensin ◽  
Lv Dysfunction ◽  
17Β Estradiol ◽  
The Brain

The present study tested the hypothesis that 17β-estradiol (E2) inhibits increases in angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT1R) in the brain and heart after myocardial infarction (MI) and, thereby, inhibits development of left ventricular (LV) dysfunction after MI. Age-matched female Wistar rats were treated as follows: 1) no surgery (ovary intact), 2) ovariectomy + subcutaneous vehicle treatment (OVX + Veh), or 3) OVX + subcutaneous administration of a high dose of E2 (OVX + high-E2). After 2 wk, rats were randomly assigned to coronary artery ligation (MI) and sham operation groups and studied after 3 wk. E2 status did not affect LV function in sham rats. At 2–3 wk after MI, impairment of LV function was similar across MI groups, as measured by echocardiography and direct LV catheterization. LV ACE mRNA abundance and activity were increased severalfold in all MI groups compared with respective sham animals and to similar levels across MI groups. In most brain nuclei, ACE and AT1R densities increased after MI. Unexpectedly, compared with the respective sham groups the relative increase was clearest (20–40%) in OVX + high-E2 MI rats, somewhat less (10–15%) in ovary-intact MI rats, and least (<10–15%) in OVX + Veh MI rats. However, because in the sham group brain ACE and AT1R densities increased in the OVX + Veh rats and decreased in the OVX + high-E2 rats compared with the ovary-intact rats, actual ACE and AT1R densities in most brain nuclei were modestly higher (<20%) in OVX + Veh MI rats than in the other two MI groups. Thus E2 does not inhibit upregulation of ACE in the LV after MI and amplifies the percent increases in ACE and AT1R densities in brain nuclei after MI, despite E2-induced downregulation in sham rats. Consistent with these minor variations in the tissue renin-angiotensin system, during the initial post-MI phase, E2 appears not to enhance or hinder the development of LV dysfunction.

scholarly journals Five months of voluntary wheel running downregulates skeletal muscle LINE-1 gene expression in rats

2019 ◽  
Vol 317 (6) ◽  
pp. C1313-C1323 ◽  
Author(s):  
Matthew A. Romero ◽  
Petey W. Mumford ◽  
Paul A. Roberson ◽  
Shelby C. Osburn ◽  
Hailey A. Parry ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Exercise Training ◽  
Mrna Expression ◽  
Wheel Running ◽  
Mobile Dna ◽  
Voluntary Wheel Running ◽  
L6 Myotubes ◽  
Voluntary Wheel

Transposable elements (TEs) are mobile DNA and constitute approximately half of the human genome. LINE-1 (L1) is the only active autonomous TE in the mammalian genome and has been implicated in a number of diseases as well as aging. We have previously reported that skeletal muscle L1 expression is lower following acute and chronic exercise training in humans. Herein, we used a rodent model of voluntary wheel running to determine whether long-term exercise training affects markers of skeletal muscle L1 regulation. Selectively bred high-running female Wistar rats ( n = 11 per group) were either given access to a running wheel (EX) or not (SED) at 5 wk of age, and these conditions were maintained until 27 wk of age. Thereafter, mixed gastrocnemius tissue was harvested and analyzed for L1 mRNA expression and DNA content along with other L1 regulation markers. We observed significantly ( P < 0.05) lower L1 mRNA expression, higher L1 DNA methylation, and less L1 DNA in accessible chromatin regions in EX versus SED rats. We followed these experiments with 3-h in vitro drug treatments in L6 myotubes to mimic transient exercise-specific signaling events. The AMP-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR; 4 mM) significantly decreased L1 mRNA expression in L6 myotubes. However, this effect was not facilitated through increased L1 DNA methylation. Collectively, these data suggest that long-term voluntary wheel running downregulates skeletal muscle L1 mRNA, and this may occur through chromatin modifications. Enhanced AMPK signaling with repetitive exercise bouts may also decrease L1 mRNA expression, although the mechanism of action remains unknown.

Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Matthias Koch ◽  
Klaus Bonaventura ◽  
Frank Spillmann ◽  
Andreas Dendorfer ◽  
Heinz-Peter Schultheiss ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ace Inhibitor ◽  
Diastolic Pressure ◽  
Ace Inhibition ◽  
Left Ventricular ◽  
Brown Norway ◽  
Lv Function ◽  
Maximal Rate ◽  
Lv Dysfunction

Abstract Bradykinin (BK) coronary outflow and left ventricular (LV) performance of kininogen-deficient Brown Norway Katholiek (BNK) rats and Brown Norway Hannover (BNH) controls were investigated. We analyzed whether the angiotensin-converting enzyme (ACE) inhibitor ramipril is able to attenuate LV dysfunction after induction of myocardial infarction (MI) in this animal model. Ex vivo, the basal BK content in the coronary outflow of buffer-perfused, isolated hearts was measured by specific radioimmunoassay. In vivo, left ventricular pressure (LVP), the maximal rate of LVP increase, LV end-diastolic pressure, the maximal rate of LVP decrease and heart rate were determined using a tip catheter 3 weeks after induction of MI. Compared to BNK rats, basal BK outflow was increased 30-fold in controls (p<0.01). In vivo, we found no significant differences between sham-ligated BNK and BNH rats in basal LV function. After MI, the impairment of LV function was significantly worse in BNK rats when compared to BNH rats. ACE inhibition significantly attenuated this LV dysfunction in both groups, when compared to untreated animals. Reduced basal BK level resulting from kininogen deficiency has no effect on basal LV function, but remains to be a risk factor for the ischemic heart. However, ACE inhibition is sufficient to improve LV function despite kininogen deficiency.

scholarly journals Voluntary exercise and depression-like behavior in rodents: are we running in the right direction?

2018 ◽  
Vol 60 (3) ◽  
pp. R77-R95 ◽  
Author(s):  
Joram D Mul
Keyword(s):  
Exercise Training ◽  
Molecular Mechanisms ◽  
Wheel Running ◽  
Financial Burden ◽  
Modern Society ◽  
Mental Illnesses ◽  
Voluntary Exercise ◽  
Voluntary Wheel Running ◽  
Beneficial Effects ◽  
Voluntary Wheel

Acute or chronic exposure to stress can increase the risk to develop major depressive disorder, a severe, recurrent and common psychiatric condition. Depression places an enormous social and financial burden on modern society. Although many depressed patients are treated with antidepressants, their efficacy is only modest, underscoring the necessity to develop clinically effective pharmaceutical or behavioral treatments. Exercise training produces beneficial effects on stress-related mental disorders, indicative of clinical potential. The pro-resilient and antidepressant effects of exercise training have been documented for several decades. Nonetheless, the underlying molecular mechanisms and the brain circuitries involved remain poorly understood. Preclinical investigations using voluntary wheel running, a frequently used rodent model that mimics aspects of human exercise training, have started to shed light on the molecular adaptations, signaling pathways and brain nuclei underlying the beneficial effects of exercise training on stress-related behavior. In this review, I highlight several neurotransmitter systems that are putative mediators of the beneficial effects of exercise training on mental health, and review recent rodent studies that utilized voluntary wheel running to promote our understanding of exercise training-induced central adaptations. Advancements in our mechanistic understanding of how exercise training induces beneficial neuronal adaptations will provide a framework for the development of new strategies to treat stress-associated mental illnesses.

P5011Impact of guideline-recommended medical therapy at discharge on long-term mortality in patients with or without left ventricular dysfunction after primary PCI for STEMI

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Radomirovic ◽  
D Milasinovic ◽  
Z Mehmedbegovic ◽  
D Jelic ◽  
V Zobenica ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Beta Blocker ◽  
Beta Blockers ◽  
Left Ventricular ◽  
Lv Function ◽  
Primary Pci ◽  
Lv Dysfunction ◽  
Concurrent Use ◽  
Tertiary Center ◽  
The Impact

Abstract Background Clinical practice guidelines provide class I recommendation for the use of angiotensin-converting enzyme inhibitors (ACE-I) and beta-blockers in patients with prior myocardial infarction and left ventricular (LV) dysfunction, whereas their use in patients without LV dysfunction is considered to be a class IIa recommendation. Purpose Our aim was to comparatively assess the impact of ACE-I and/or beta-blockers on 3-year mortality in patients with or without impaired left ventricular (LV) function undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Methods The analysis included 4425 patients admitted for primary PCI during 2009–2015 from a prospective, electronic registry of a high-volume tertiary center, who survived initial hospitalization, and for whom information on LV function and discharge medication were available. Patients were stratified according to LV systolic dysfunction, defined as LVEF <40%. Unadjusted and adjusted Cox regression models were created to investigate the impact of beta-blocker and/or ACE-I therapy on 3-year mortality. Results 22.9% (n=1013) had LV dysfunction, 23.0% (n=1017) received either an ACE-I or a beta-blocker and 72.2% received both medications at discharge (n=3197). The concurrent use of both ACE-I and beta-blockers was not different in LVEF≥40% vs. LVEF<40% (72.4% vs. 71.7%, p=0.43). The use of at least one of the guideline-recommended medications was associated with a significantly lower 3-year mortality in both patients with LVEF≥40% (18.7% if neither was used, 11.2% if either a beta-blocker or an ACE-I were used and 9.4% if both were used, p=0.001), and LVEF<40% (55.4% if neither was used, 32.5% if either a beta-blocker or an ACE-I were used and 22.9% if both were used, p<0.001) (Figure). After adjusting for significant mortality predictors including older age, diabetes, hypertension, renal failure, previous stroke, Killip class ≥2 and non-culprit chronic total occlusion (CTO), the concurrent use of both a beta-blocker and an ACE-I remained independently associated with lower 3-year mortality in both patients with LVEF<40% (HR 0.30, p<0.001) and LVEF≥40% (HR=0.41, p=0.001). The use of a single agent was independently associated with lower mortality in patients with LVEF<40% (HR 0.45, p=0.002), but not in patients with LVEF≥40% (HR 0.61, p=0.07). Conclusions Guideline-recommended use of both a beta-blocker and an ACE-I in post-MI patients was associated with a lower 3-year mortality regardless of the LV function, whereas using only one of the two agents was associated with improved prognosis only in patients with LV dysfunction, but not in patients without LV impairment.

scholarly journals Cardiac function is preserved following 4 weeks of voluntary wheel running in a rodent model of chronic kidney disease

2014 ◽  
Vol 117 (5) ◽  
pp. 482-491 ◽  
Author(s):  
James M. Kuczmarski ◽  
Christopher R. Martens ◽  
Jahyun Kim ◽  
Shannon L. Lennon-Edwards ◽  
David G. Edwards
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Voluntary Wheel Running ◽  
Low Volume ◽  
Voluntary Wheel

The purpose of this investigation was to determine the effect of 4 wk of voluntary wheel running on cardiac performance in the 5/6 ablation-infarction (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary wheel running would be effective in preserving cardiac function in AI. Male Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI. Animals were maintained over a total period of 8 wk following AI and sham surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk voluntary wheel-running intervention/sedentary control period. Cardiac performance was assessed using an isolated working heart preparation. Left ventricular (LV) tissue was used for biochemical tissue analysis. In addition, soleus muscle citrate synthase activity was measured. AI-WR rats performed a low volume of exercise, running an average of 13 ± 2 km, which resulted in citrate synthase activity not different from that in sham animals. Isolated AI-SED hearts demonstrated impaired cardiac performance at baseline and in response to preload/afterload manipulations. Conversely, cardiac function was preserved in AI-WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO) synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In addition, LV H2O2 in AI-WR was similar to that of sham and associated with increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2. The findings of the current study suggest that a low-volume exercise intervention is sufficient to maintain cardiac performance in rats with CKD, potentially through a mechanism related to improved redox homeostasis and increased NO.

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