The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure

2001 ◽  
Vol 280 (4) ◽  
pp. H1853-H1860 ◽  
Author(s):  
Che-Ping Cheng ◽  
Tomohiko Ukai ◽  
Katsuya Onishi ◽  
Nobuyuki Ohte ◽  
Makoto Suzuki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Combined Treatment ◽  
Left Ventricular ◽  
Ang Ii ◽  
Systolic Volume ◽  
Minimum Pressure ◽  
Endothelin 1 ◽  
Before And After ◽  
Very High

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (τ), LV end-systolic volume (VES), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, τ, and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT1-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest.

Abstract 16639: A Novel Approach to Model Heart Failure With Preserved Ejection Fraction in Rats

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kenichi Katsurada ◽  
Shyam S Nandi ◽  
Neeru M Sharma ◽  
Kaushik P Patel
Keyword(s):  
Heart Failure ◽  
Mean Arterial Pressure ◽  
Ejection Fraction ◽  
Arterial Pressure ◽  
Diastolic Dysfunction ◽  
Unit Area ◽  
Isotonic Saline ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Ang Ii

Introduction: Diastolic dysfunction and cardiac hypertrophic remodeling are hallmark features of heart failure with preserved ejection fraction (HFpEF) in humans. However, an ideal animal model that mimics all these basic clinical features of HFpEF remains to be developed. Methods: Male Sprague-Dawley rats (250-300 g) were subjected to central infusion of either Angiotensin II (Ang II at 20 ng/min, 0.5 μl/h, i.c.v) or isotonic saline (0.5 μl/h, i.c.v) through osmotic mini-pumps for 14 days. Echocardiography was used to measure systolic (ejection fraction) and diastolic functions (E/A and E/E’ ratio) at day 14. Mean arterial pressure (MAP), heart rate (HR), left ventricular pressure (LVP), changes in ±dP/dt, and cardiac responses to isoproterenol (ISO) were also measured in anesthetized rats. Results: Central infusion of Ang II in rats resulted in increased sympathoexcitation and mean arterial pressure. Concomitantly, there was decreased E/A ratio (AngII: 1.2 ± 0.1 vs. Cont: 1.5 ± 0.1) and increased E/E’ ratio (AngII: 14.3 ± 0.8 vs. Cont: 12.9 ± 0.6), indicating diastolic dysfunction. Ejection fractions were comparable between the groups (AngII: 67 ± 2% vs. Cont: 69 ± 5%). Ang II infused rats demonstrated increased heart to body weight ratio (AngII: 4.5 ± 0.5 vs. Cont: 2.9 ± 0.1), cachexia (AngII: 235 ± 18 g vs. Cont: 331 ± 11 g), hypertrophy (AngII: 46 ± 5 μm/unit area vs. Cont: 36 ± 7 μm/unit area), and fibrosis (AngII: 5.2 ± 0.5 intensity/unit area vs. Cont: 2.6 ± 0.4 intensity/unit area). At the same time cardiac contractile responsiveness to ISO (0.5 μg/kg) was significantly lower for negative dP/dt in Ang II rats (AngII: -6998 mmHg/s vs. Cont: -11675 mmHg/s), which is indicative of abnormal diastole or relaxation. However, positive dP/dt response to ISO was similar in the two groups, indicating preserved systolic function in the Ang II group. Conclusions: Central Ang II infusion in rats shows sympathoexcitation, diastolic dysfunction, and pathological cardiac hypertrophy and fibrosis mimicking abnormalities seen in patients with HFpEF. This model of cardiac dysfunction in rats may represent a suitable platform to investigate the underlying mechanisms of HFpEF.

A Systematic Review and Meta-analysis : Safety and Efficacy of Mesenchymal stem Cells Therapy for Heart Failure

2020 ◽  
Vol 15 ◽  
Author(s):  
Tiantian Shen ◽  
Lin Xia ◽  
Wenliang Dong ◽  
Jiaxue Wang ◽  
Feng Su ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Safety And Efficacy ◽  
Systolic Volume ◽  
End Diastolic Volume ◽  
End Systolic Volume

Background: Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating heart failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy is not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients. Methods: We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized controlled trials(RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model when it appropriate by use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess bias of included studies. The primary outcome was safety assessed by death and rehospitalization and the secondary outcome was efficacy which was assessed by six-minute walk distance and left ventricular ejection fraction (LVEF)，left ventricular end-systolic volume（LVESV），left ventricular end-diastolic volume（LVEDV） and brain natriuretic peptide（BNP） Results: A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT.MSCs transplantation significantly improved left ventricular ejection fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased left ventricular end-systolic volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, -12.83], p<0.00001 ) and left ventricular end-diastolic volume (LVEDV) by 5.78 ml (MD [95% CI]=-5.78[-12.00, 0.43], p=0.07 ) ,in the MSCs group , BNP was decreased by 133.51 pg/ml MD [95% CI]= -133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group. Conclusions: Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure is safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*10^8 cells were of better effect.

scholarly journals Implications of multiple late gadolinium enhancement lesions on the frequency of left ventricular reverse remodeling and prognosis in patients with non‐ischemic cardiomyopathy

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shingo Ota ◽  
Makoto Orii ◽  
Tsuyoshi Nishiguchi ◽  
Mao Yokoyama ◽  
Ryoko Matsushita ◽  
...  
Keyword(s):  
Heart Failure ◽  
Late Gadolinium Enhancement ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Cardiac Events ◽  
Gadolinium Enhancement ◽  
Systolic Volume ◽  
Linear Pattern ◽  
Multiple Lesions

Abstract Background Non-ischemic cardiomyopathy (NICM) is a heterogeneous disease, and its prognosis varies. Although late gadolinium enhancement (LGE)-cardiovascular magnetic resonance (CMR) demonstrates a linear pattern in the mid-wall of the septum or multiple LGE lesions in patients with NICM, the therapeutic response and prognosis of multiple LGE lesions have not been elucidated. This study aimed to investigate the frequency of left ventricular (LV) reverse remodeling (LVRR) and prognosis in patients with NICM who have multiple LGE lesions. Methods This single-center retrospective study included 101 consecutive patients with NICM who were divided into 3 groups according to LGE-CMR results: patients without LGE (no LGE group = 48 patients), patients with a typical mid-wall LGE pattern (n = 29 patients), and patients with multiple LGE lesions (n = 24 patients). LVRR was defined as an increase in LV ejection fraction (LVEF) ≥ 10 % and a final value of LVEF > 35 %, which was accompanied by a decrease in LV end-systolic volume ≥ 15 % at 12-month follow-up using echocardiography. The frequency of composite cardiac events, defined as sudden cardiac death (SCD), aborted SCD (non-fatal ventricular fibrillation, sustained ventricular tachycardia, or adequate implantable cardioverter-defibrillator therapies), and heart failure death or hospitalization for worsening heart failure, were summarized and compared between the groups. Results Among the 3 groups, the frequency of LVRR was significantly lower in the multiple lesions group than in the no LGE and mid-wall groups (no LGE vs. mid-wall vs. multiple lesions: 49 % vs. 52 % vs. 19 %, p = 0.03). There were 24 composite cardiac events among the patients: 2 in patients without LGE (hospitalization for worsening heart failure; 2), 7 in patients of the mid-wall group (SCD; 1, aborted SCD; 1 and hospitalization for worsening heart failure; 5), and 15 in patients of the multiple lesions group (SCD; 1, aborted SCD; 8 and hospitalization for worsening heart failure; 6). The multiple LGE lesions was an independent predictor of composite cardiac events (hazard ratio: 11.40 [95 % confidence intervals: 1.49−92.01], p = 0.020). Conclusions Patients with multiple LGE lesions have a higher risk of cardiac events and poorer LVRR. The LGE pattern may be useful for an improved risk stratification in patients with NICM.

Estimation of Left Ventricular Wall Stiffness by Analysis of Late Diastolic Pressure Components

2011 ◽  
Author(s):  
Casandra L. Niebel ◽  
Kelley C. Stewart ◽  
Takahiro Ohara ◽  
John J. Charonko ◽  
Pavlos P. Vlachos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Diastolic Dysfunction ◽  
Diastolic Pressure ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Ventricular Wall ◽  
Ventricular Relaxation ◽  
Wall Stiffness ◽  
Ventricular Diastolic Dysfunction

Left ventricular diastolic dysfunction (LVDD) is any abnormality in the filling of the left ventricle and is conventionally evaluated by analysis of the relaxation driven phase, or early diastole. LVDD has been shown to be a precursor to heart failure and the diagnosis and treatment for diastolic failure is less understood than for systolic failure. Diastole consists of two filling waves, early and late and is primarily dependent on ventricular relaxation and wall stiffness.

scholarly journals Pulmonary Hypertension in Heart Failure Patients Presenting at OAUTHC, Ile-Ife, Nigeria

2016 ◽  
Vol 10 ◽  
pp. CMC.S38447
Author(s):  
Valentine N. Amadi ◽  
Olufemi E. Ajayi ◽  
Anthony O. Akintomide ◽  
Olugbenga O. Abiodun ◽  
Olaniyi J. Bamikole ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Left Ventricular ◽  
Systolic Volume ◽  
Heart Failure Patients ◽  
Mean Pulmonary Arterial Pressure ◽  
Diastolic Velocity ◽  
End Systolic Volume ◽  
Pulmonary Arterial ◽  
Systolic And Diastolic Function

Background Pulmonary hypertension (PH) is common in heart failure patients. Literature on PH in heart failure is sparse in Nigeria. This study was carried out to determine the prevalence of PH in heart failure patients and ascertain the relationship between left ventricular systolic and diastolic function and the degree of PH. Methods A total of 125 heart failure patients had echocardiography done. PH was diagnosed using tricuspid regurgitation jet and pulmonary ejection jet profile. Results PH was present in 70.4% of heart failure patients. Estimated mean pulmonary arterial pressure increased with increasing severity of systolic and diastolic dysfunction and had significantly negative correlation with ejection fraction, fractional shortening, and early mitral annular tissue diastolic velocity ( E′), but positive correlation with left ventricular end-systolic volume, right ventricular dimension, transmitral E to A ratio, and E/E′ ratio. Conclusion PH is very common in heart failure and has significant relationship with left ventricular function.

scholarly journals Features of the relationship between the parameters of left ventricular mechanics and the level of biomarkers of heart failure in patients with epicardial obesity

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
O Gritsenko ◽  
GA Chumakova
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Speckle Tracking ◽  
Left Atrial Volume ◽  
Left Ventricular ◽  
Serum Biomarker ◽  
Volume Index ◽  
Time To Peak ◽  
Ventricular Mechanics ◽  
The Relationship

Abstract Funding Acknowledgements Type of funding sources: None. Currently, there is no serum biomarker that is a marker of the presence of heart failure (HF) at an early stage. It is also shown that the traditional indicators used for the diagnosis diastolic dysfunction (DD) of left ventricular (LV) using echocardiography (ECG) are not informative enough. Thus, it is currently relevant to study new serum biomarkers of DD, such as sST2, as well as to study the mechanics of LV. Objective to study the relationship between mechanics of LV and the level of sST2 (bioamarker of HF) in patients with epicardial obesity (EO). Materials and methods The study included 110 men with general obesity. According to the results of echocardiography (ECG), patients were divided into 2 groups: EO (+) with epicardial fat thickness (tEAT) ≥7 mm (n = 70); EO (-) with tEAT &lt;7 mm (n = 40) without diastolic dysfunction according to the results of ECG. All patients were assessed for sST2 and NT-pro-BNP levels using enzyme immunoassay. Using speckle-tracking ECG, the mechanics of LV were studied (twist LV, peak twist ratio LV, time to peak twist of LV, peak untwist ratio LV, time to peak untwist of LV). The exclusion criteria were the presence of coronary pathology, arterial hypertension, and type 2 diabetes mellitus. Results In the group patients with EO ( + ) a statistically significant increase in the level of sST2 was revealed in comparison with the group of EO (-) [21,55 ng/ml (26,52; 15,40) and 9.89 ng/ml (11.12; 7.95); p = 0.001, respectively], while the levels of NT-pro-BNP in both groups were not statistically different [211.36 pg / ml (254.0; 156.0) and 204.81 pg / ml (268.0; 157.0), respectively, p = 0.85]. When determining the parameters of DD LV by ECG, there were no statistical differences between the EO (+) and EO (-) groups [e ", cm / sec 0.09 (0.11; 0.09) and 0.09 (0.11; 0.09), respectively, p = 0.63; E/e " , units, 7.80 (8.90; 6.55) in the EO (+) and 8.53 (9.70; 7.20) in the EO group ( - ), p = 0.08; left atrial volume index, ml / sq2, in the EO group (+) 28.39 (31.25; 24.17) and in the EO group(-) 27,82 (30,21; 25,66), p = 0.55; in the EO group ( + ), the maximum speed of tricuspid regurgitation, m / sec, is 2.78 (2.9; 2.58) in the EO group(-) 2,67 (2,87; 2,41), p = 0.13]. According to the results of speckle-tracking ECG in the EO (+) group, an increase peak untwist ratio LV to -128.31 (-142.0; -118.0) deg/s-1 (p = 0.002) and an increase time to peak untwist of LV of 476.44 (510.0; 411.0) msec was determined in comparison with the EO ( - ) group (p = 0.03). A significant relationship between peak untwist ratio LV and sST2 was revealed (r = 0.37; p = 0.02). Conclusion Thus, it can be assumed that patients with EO have DD LV at the preclinical stage, which is not diagnosed using traditional ECG indicators. The serum biomarker sST2 is an early marker of the presence of HF.

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.

scholarly journals Diastolic dysfunction in individuals with and without heart failure with preserved ejection fraction

2021 ◽  
Author(s):  
Jan-Per Wenzel ◽  
Ramona Bei der Kellen ◽  
Christina Magnussen ◽  
Stefan Blankenberg ◽  
Benedikt Schrage ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Cardiovascular Risk ◽  
General Population ◽  
Diastolic Dysfunction ◽  
Cardiovascular Risk Factors ◽  
Population Based ◽  
Left Ventricular ◽  
Health Study ◽  
Common Finding

Abstract Aim Left ventricular diastolic dysfunction (DD), a common finding in the general population, is considered to be associated with heart failure with preserved ejection faction (HFpEF). Here we evaluate the prevalence and correlates of DD in subjects with and without HFpEF in a middle-aged sample of the general population. Methods and results From the first 10,000 participants of the population-based Hamburg City Health Study (HCHS), 5913 subjects (mean age 64.4 ± 8.3 years, 51.3% females), qualified for the current analysis. Diastolic dysfunction (DD) was identified in 753 (12.7%) participants. Of those, 11.2% showed DD without HFpEF (ALVDD) while 1.3% suffered from DD with HFpEF (DDwHFpEF). In multivariable regression analysis adjusted for major cardiovascular risk factors, ALVDD was associated with arterial hypertension (OR 2.0, p < 0.001) and HbA1c (OR 1.2, p = 0.007). Associations of both ALVDD and DDwHFpEF were: age (OR 1.7, p < 0.001; OR 2.7, p < 0.001), BMI (OR 1.2, p < 0.001; OR 1.6, p = 0.001), and left ventricular mass index (LVMI). In contrast, female sex (OR 2.5, p = 0.006), atrial fibrillation (OR 2.6, p = 0.024), CAD (OR 7.2, p < 0.001) COPD (OR 3.9, p < 0.001), and QRS duration (OR 1.4, p = 0.005) were strongly associated with DDwHFpEF but not with ALVDD. Conclusion The prevalence of DD in a sample from the first 10,000 participants of the population-based HCHS was 12.7% of whom 1.3% suffered from HFpEF. DD with and without HFpEF showed significant associations with different major cardiovascular risk factors and comorbidities warranting further research for their possible role in the formation of both ALVDD and DDwHFpEF.

Abstract 17266: Right Atrial Volumes Changes in Tetralogy of Fallot

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Ashish Patel ◽  
Divya Shakti ◽  
Chad Blackshear
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Tetralogy Of Fallot ◽  
Surgical Repair ◽  
Left Ventricular ◽  
Right Atrial ◽  
Before And After ◽  
Ventricular Diastolic Dysfunction ◽  
And Function ◽  
Averaged Model

Introduction & Hypothesis: There is limited information on right atrial (RA) function in the congenital heart defects. RA volume and function may give insight into the right ventricle (RV) diastolic function. We sought to assess RA function in tetralogy of Fallot (TOF) patients prior to and after complete surgical repair. Methods: Infants with TOF prior to complete repair were included for retrospective chart review and offline analysis of 2-dimensional echocardiograms (echo) before and after surgical repair. RA phasic volumes and stroke volumes were calculated. All volumes were indexed to body surface area. Results: There were 40 infants with TOF (45% females), of which 70% had pulmonary stenosis, 30% pulmonary atresia. Roughly 85% and 60% had 3, or more, echo available pre- and postoperatively. Table 1 (attached) shows the patient characteristics and phasic RA volumes. The indexed RA phasic volumes were in normal range in initial echo prior to surgery. We used normal index RA phasic volumes published by European Society of Echocardiography. There was the increasing trend of indexed RA phasic volume on follow up echo immediately before TOF repair. These phasic volumes continued to remain elevated after complete surgical repair (Table 1). Trends in RA stroke volumes for all available echos before and after surgery were modeled using a population-averaged model with an exchangeable within-panel correlation structure (Figure 2), showing no statistically significant difference after surgery. But there was statistical significance noted in RA ejection fraction. Please see attached image for statistical analysis and results of the study. Conclusions: The indexed RA phasic volumes in children with TOF are normal initially and increases before TOF repair and it continued to increase after TOF repair. The increase RA phasic volumes suggest RV diastolic dysfunction similar to the findings of LA phasic volumes and left ventricular diastolic dysfunction. Our findings indicate slow worsening RV diastolic function in patients with TOF after surgical repair. RA volume and function can be the novel marker to diagnose and monitor right ventricular diastolic dysfunction.

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