Abstract 15: The Cardio-renal Effects Of Il-33 Treatment In Myocardial Infarction-induced Kidney Damage

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ghadir Amin ◽  
Nada Habeichi ◽  
Rana Ghali ◽  
George W Booz ◽  
Ziad Mallat ◽  
...  

Introduction: Interleukin (IL)-33 is a nuclear alarmin released upon tissue damage and initiating a signaling cascade by binding to its cell membrane receptor ST2. Accumulating evidence shows that the IL-33/ST2 axis mediates both inflammatory and repair responses in different models of kidney diseases, suggesting a Janus-like effect that varies within disease context and progression. This study aimed to investigate the effect of IL-33 administration on acute kidney damage at 4 and 7 days post-MI in mice. Methods: MI was induced by ligating the left anterior descending coronary artery, followed by IL-33 (1μg/day)/vehicle (PBS) treatment for 4 and 7 consecutive days. Cardiac systolic function was assessed, and kidneys were subjected to histological and molecular analysis. Results: IL-33 had no significant effect on cardiac hemodynamic parameters at 4 days but significantly decreased the left ventricular ejection fraction (20 ± 1 vs 9.8 ± 2, P<0.01) at 7 days post-MI. In the kidneys, reduced glomerular retraction (0.57 ± 0.09 vs 0.24 ± 0.06, P < 0.05) was observed at day 4 post-MI only, along with a decrease in the protein expression of αSMA (2.89 ± 0.33 vs 0.43 ± 0.13, P < 0.001) and collagen 3 (1.96 ± 0.78 vs 0.34 ± 0.14, P < 0.05). Conversely, increased protein levels of αSMA (0.86 ± 0.42 vs 21.5 ± 2.53, P < 0.0001) and collagen 3 (0.33 ± 0.08 vs 1.71 ± 0.22, P<0.01) were observed at day 7 post-MI. Total renal fibrosis increased to levels comparable to the MI vehicle group at day 4 and 7 post-MI. The mRNA expression of the apoptotic BAX/BCL2 ratio (1.05 ± 0.09 vs 0.36 ± 0.23, P < 0.05) decreased only at day 4 post-MI, whereas an increase in the mRNA levels of the DNA repair enzyme PARP-1 (1.37 ± 0.06 vs 2.05 ± 0.4, P<0.05) was observed at day 7 post-MI. A marked increase in the mRNA expression of Sirtuin 3 (1.87 ± 0.57 vs 11.72 ± 4.24, P < 0.05) and in total renal NAD levels (386.75 ± 40.52 vs 706.36 ± 66.09, P < 0.05) was observed at day 4 post-MI. Conclusion: Collectively, our findings suggest that although IL-33 treatment improves renal homeostasis 4 days post-MI, this protection is offset by day 7 post-MI through enhanced renal morphological and molecular alterations. The observed renal deterioration between day 4 and day 7 post-MI correlate with aggravated cardiac dysfunction.

2002 ◽  
Vol 102 (4) ◽  
pp. 381-386 ◽  
Author(s):  
Mamoru SATOH ◽  
Motoyuki NAKAMURA ◽  
Hidenori SAITOH ◽  
Hidetoshi SATOH ◽  
Tomonari AKATSU ◽  
...  

The pathway of tissue aldosterone production may exist in the heart, and may be an important contributory factor to myocardial fibrosis and cardiac remodelling in the failing heart. CYP11B2 (aldosterone synthase) catalyses the final step of aldosterone production. The aim of the present study was to determine whether CYP11B2 and CYP11B1 (11β-hydroxylase) are expressed in myocardial tissues, and whether these enzymes contribute to collagen accumulation and myocardial dysfunction in the failing human heart. Endomyocardial tissues were obtained from 23 patients with chronic heart failure (CHF) and 10 controls. CYP11B2 and CYP11B1 mRNA levels were measured by real-time quantitative reverse transcriptase-PCR. The myocardial collagen volume fraction (CVF) was determined by digital planimetry. CYP11B2 mRNA expression was greater in the CHF group than in the controls (P < 0.05), while CYP11B1 mRNA was barely expressed in either group. There was a positive correlation between CYP11B2 mRNA levels and CVF (r = 0.64, P =0.001). CYP11B2 mRNA was particularly highly expressed in subgroups of CHF patients with a large left ventricular end-systolic diameter (>55mm) or a low left ventricular ejection fraction (< 30%). CYP11B2 mRNA expression and CVF were lower in a CHF subgroup treated with a combination of spironolactone and angiotensin-converting enzyme inhibitors (ACEIs) than in a subgroup not treated with these drugs. In conclusion, this study has shown that increased myocardial expression of CYP11B2 mRNA is associated with increased myocardial fibrosis and with the severity of left ventricular dysfunction in human CHF. In addition, CYP11B2 expression and cardiac fibrosis are found to be decreased in CHF patients on drug therapy comprising spironolactone combined with ACEIs.


2011 ◽  
pp. 62-70
Author(s):  
Lien Nhut Nguyen ◽  
Anh Vu Nguyen

Background: The prognostic importance of right ventricular (RV) dysfunction has been suggested in patients with systolic heart failure (due to primary or secondary dilated cardiomyopathy - DCM). Tricuspid annular plane systolic excursion (TAPSE) is a simple, feasible, reality, non-invasive measurement by transthoracic echocardiography for evaluating RV systolic function. Objectives: To evaluate TAPSE in patients with primary or secondary DCM who have left ventricular ejection fraction ≤ 40% and to find the relation between TAPSE and LVEF, LVDd, RVDd, RVDd/LVDd, RA size, severity of TR and PAPs. Materials and Methods: 61 patients (36 males, 59%) mean age 58.6 ± 14.4 years old with clinical signs and symtomps of chronic heart failure which caused by primary or secondary DCM and LVEF ≤ 40% and 30 healthy subject (15 males, 50%) mean age 57.1 ± 16.8 were included in this study. All patients and controls were underwent echocardiographic examination by M-mode, two dimentional, convensional Dopler and TAPSE. Results: TAPSE is significant low in patients compare with the controls (13.93±2.78 mm vs 23.57± 1.60mm, p<0.001). TAPSE is linearly positive correlate with echocardiographic left ventricular ejection fraction (r= 0,43; p<0,001) and linearly negative correlate with RVDd (r= -0.39; p<0.01), RVDd/LVDd (r=-0.33; p<0.01), RA size (r=-0.35; p<0.01), TR (r=-0.26; p<0.05); however, no correlation was found with LVDd and PAPs. Conclusions: 1. Decreased RV systolic function as estimated by TAPSE in patients with systolic heart failure primary and secondary DCM) compare with controls. 2. TAPSE is linearly positive correlate with LVEF (r= 0.43; p<0.001) and linearly negative correlate with RVDd (r= -0.39; p<0.01), RVDd/LVDd (r=-0.33; p<0.01), RA size (r=-0.35; p<0.01), TR (r=-0.26; p<0.05); however, no correlation is found with LVDd and PAPs. 3. TAPSE should be used routinely as a simple, feasible, reality method of estimating RV function in the patients systolic heart failure DCM (primary and secondary).


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Marcos Garces ◽  
C Rios-Navarro ◽  
L Hueso ◽  
A Diaz ◽  
C Bonanad ◽  
...  

Abstract Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models, functional and structural implication of VEGF-A165b blockade was assessed. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6-months and with the occurrence of adverse events (death, heart failure and/or re-infarction). Results In both models, circulating and myocardial VEGF-A165b presence was increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockage increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in non-reperfused MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels associates with a worse systolic function. Its blockage enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in non-reperfused MI experiments. Therefore, VEGF-A165b neutralization represents a potential co-adjuvant therapy to coronary reperfusion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (Exp. PIE15/00013, PI17/01836, PI18/00209 and CIBERCV16/11/00486).


2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
C Rios-Navarro ◽  
J Gavara ◽  
J Nunez ◽  
C Bonanad Lozano ◽  
E Revuelta-Lopez ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” Bachground. Microvascular obstruction (MVO) is negatively associated with cardiac structure and worse prognosis after ST-segment elevation myocardial infarction (STEMI). Epithelial cell adhesion molecule (EpCAM), involved in endothelium adhesion, is an understudied area in the MVO setting. Purpose. We aimed to evaluate whether EpCAM is associated with the appearance of cardiac magnetic resonance (CMR)-derived MVO and long-term systolic function in reperfused STEMI. Methods. We prospectively included 106 patients with a first STEMI treated with primary percutaneous coronary intervention, quantifying serum levels of EpCAM 24 hours post-reperfusion. All patients underwent CMR imaging 1 week and 6 months post-STEMI. The independent correlation of EpCAM with MVO, systolic volume indices, and left ventricular ejection fraction (LVEF) was evaluated. Results. The mean age of the sample was 59 ± 13 years and 76% were male. Patients were dichotomized according to EpCAM median (4.48 pg/mL). At 1-week CMR, lower EpCAM was related to extensive MVO (p-value = 0.02) and greater infarct size (p-value = 0.02). At presentation, only EpCAM values were significantly associated with the presence of MVO in univariate (Odds Ratio [95% confidence interval] (OR [95% CI]): 0.58 [0.38-0.88], p-value = 0.01) and multivariate logistic regression models (OR [95% CI]: 0.54 [0.34-0.85], p-value = 0.007). Although MVO tends to resolve at chronic phases, decreased EpCAM was associated with worse systolic function: depressed LVEF (p-value = 0.009) and higher left ventricular end-systolic volume (p-value = 0.04). Conclusions. EpCAM is associated with occurrence of CMR-derived MVO at acute phases and long-term adverse ventricular remodeling post-STEMI. Future studies are needed to confirm EpCAM as biomarker, and eventually biotarget in STEMI pathophysiology.


2018 ◽  
Vol 47 (5) ◽  
pp. 361-371 ◽  
Author(s):  
Qing Kuang ◽  
Ning Xue ◽  
Jing Chen ◽  
Ziyan Shen ◽  
Xiaomeng Cui ◽  
...  

Background: Chronic kidney disease (CKD) has been proposed to associate with decreased hydrogen sulfide (H2S) level. Nevertheless, the role of H2S in the pathogenesis of CKD has not been fully investigated. Our study aimed to investigate the plasma level of endogenous H2S in patients with different stages of CKD, and to identify the role of H2S in the progression of CKD and its relationship with cardiovascular diseases. Methods: A total of 157 non-dialysis CKD patients were recruited in our study, with 37 age- and sex-matched healthy individuals as control. Plasma concentration of H2S was measured with spectrophotometry. Sulfhemoglobin, the integration of H2S and hemoglobin, was characterized and measured by dual wavelength spectrophotometry. Serum levels of homocysteine (Hcy), cardiac troponin T (cTnT), and N-terminal pro B type natriuretic peptide were measured using automated analyzers. Conventional transthoracic echocardiography was performed and left ventricular ejection fraction (LVEF) was analyzed as a sensitive parameter of cardiac dysfunction. Results: The plasma H2S level (μmol/L) in CKD patients was significantly lower than those in healthy controls (7.32 ± 4.02 vs. 14.11 ± 5.24 μmol/L, p < 0.01). Plasma H2S level was positively associated with estimated glomerular filtration rate (eGFR; ρ = 0.577, p < 0.01) and negatively associated with plasma indoxyl sulfate concentration (ρ = –0.554, p < 0.01). The mRNA levels of cystathionine β-synthase and cystathionine γ-lyase, 2 catalytic enzymes of H2S formation, were significantly lower in blood mononuclear cells of CKD patients with respect to controls; however, the mRNA level of 3-mercaptopyruvate sulfurtransferase, as another H2S-producing enzyme, was significantly higher in CKD patients. The serum concentration of Hcy, acting as the substrate of H2S synthetase, was higher in the CKD group (p < 0.01). Specifically, the content of serum Hcy in CKD stages 3–5 patients was significantly higher than that in CKD stages 1–2, indicating an increasing trend of serum Hcy with the decline of renal function. Examination of ultrasonic cardiogram revealed a negative ­correlation between plasma H2S level and LVEF (ρ = –0.204, p < 0.05) in CKD patients. The H2S level also correlated negatively with cTnT concentration (ρ = –0.249, p < 0.01). Conclusions: Plasma H2S level decreased with the decline of eGFR, which may contribute to the cardiac dysfunction in CKD ­patients.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
John R Kapoor ◽  
Paul A Heidenreich

Several large cohort studies document better survival in heart failure patients with decreased left ventricular ejection fraction (EF) and higher body mass index (BMI) compared to those with a lower BMI. It is unclear, though, if this “obesity paradox” applies to heart failure patients with preserved EF or if it extends to the very obese (BMI>35). We followed 1,235 consecutive patients with a prior diagnosis of heart failure and a preserved EF (≥50%) documented on echocardiography at one of three laboratories. We determined adjusted mortality and readmission rates at 1 year following the echocardiogram. Obesity (BMI>30) was noted in 542 patients (44%). The mean age of the cohort was 71 years, but this varied depending on BMI (73 years for BMI<25, 64 years for BMI> 35, p< 0.001). In a subset of patients with complete diastolic indices and LV mass measurements (n=405), 95% had objective evidence of diastolic dysfunction. Age-adjusted all-cause mortality (Figure ) at one year decreased with increasing BMI (31% if BMI < 25, 22% if BMI 25–29, 20% if BMI 30–35 and 19% if BMI>35, p=0.003). In a proportional hazards analysis that adjusted for patient history, demographics and laboratory values, the hazard ratios for total mortality (relative to a normal BMI) were 1.47 (95% CI, 1.06–2.05) for BMI<25, 0.95 (95% CI, 0.64 –1.42) for BMI 30 –35, and 0.83 (95% CI, 0.52–1.31), for BMI >35, p=0.046). Similar findings were noted for the composite endpoint of survival free from heart failure hospitalization. These data suggest that the obesity paradox applies to heart failure patients with preserved systolic function and extends to very obese patients (BMI>35).


2019 ◽  
Vol 12 (1) ◽  
pp. 24-29
Author(s):  
Mohammad Jakir Hossain ◽  
Khondoker Asaduzzaman ◽  
Solaiman Hossain ◽  
Muhammad Badrul Alam ◽  
Nur Hossain

Background: In the diagnosis of acute coronary syndrome, cardiac troponin I is highly reliable and widely available biomarker. Serum level of cardiac troponin I is related to amount of myocardial damage and also closely relates to infarct size. Our aim of the study is to find out the relationship between cardiac troponin I and left ventricular systolic function after acute coronary syndrome. Methods: Total of 132 acute coronary syndrome patients were included in this study after admission in coronary care unit of Sir Salimullah Medical College, Mitford Hospital. Troponin I level was measured at admission and left ventricular ejection fraction (LVEF) was measured by echocardiography between 12-48 hours of onset of chest pain. Results: There was negative correlation between Troponin I at 12 to 48 hours of chest pain with LVEF in these study patients. With a cutoff value of troponin I e”6.8 ng/ml in STEMI patients there is a significant negative relation between 12 to 48 hrs troponin I and LVEF (p<0.001). Sensitivity of troponin I e” 6.8 ng/ml between 12 to 48 hours of chest pain in predicting LVEF <50% in STEMI was 93.75% and specificity was 77.78%. In NSTEMI sensitivity of troponin I e” 4.5 ng/ml between 12 to 48 hours of chest pain in predicting LVEF <50% was 65% and specificity was 54.05%. Conclusion: Serum troponin I level had a strong negative correlation with left ventricular ejection fraction after acute coronary syndrome and hence can be used to predict the LVEF in this setting. Cardiovasc. j. 2019; 12(1): 24-29


Heart Asia ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. e011043
Author(s):  
Muhammad Salman Ghazni ◽  
Saba Aijaz ◽  
Rehan Malik ◽  
Asad Z Pathan

Heart failure with reduced left ventricular ejection fraction (HFrEF) is a frequently encountered clinical scenario. Coronary angiography (CAG) is usually performed to assess obstructive epicardial coronary artery disease (CAD) and the resultant ischaemia as causes of HFrEF.ObjectivesTo determine the frequency of obstructive CAD (OCAD) in patients with HFrEF and its independent predictors and outcomes.MethodsRetrospective observational study in Tabba Heart Institute on patients who underwent CAG during the past 4 years. Patients with prior known CAD or revascularisation were excluded. OCAD was defined as per the criteria from Felker et al. Regression modelling was performed to evaluate the predictors of OCAD. Survival was compared between the groups using the log rank test.ResultsOut of 2235 patients who underwent CAG, 260 had HFrEF as a primary indication for CAG and, of these, 119 (45.8%) had OCAD. Major predictors of OCAD were age >50 years at presentation (OR 2.0, 95% CI 1.1 to 3.7), presence of chest pain (OR 4.3, 95% CI 2.3 to 8.1), family history of premature CAD (OR 2.8, 95% CI 1.3 to 5.9) and utilisation of non-invasive (NIV) stress testing before CAG (OR 3.6, 95% CI 1.8 to 7.1). Survival was significantly lower (log rank p<0.001) in patients with OCAD with no revascularisation compared with OCAD with revascularisation or those who had non-obstructive CAD, and the latter two groups had comparable survival.ConclusionsOCAD is detected in nearly half of the patients with reduced left ventricular systolic function undergoing CAG. Clinical judgement based on thorough history and use of NIV stress testing can help in appropriate patient selection for this test.


2017 ◽  
Vol 4 (3) ◽  
pp. 66
Author(s):  
Guramrinder S Thind ◽  
Prashant Patel ◽  
Sandeep Patri ◽  
Yashwant Agrawal

Takotsubo cardiomyopathy (TTC) is a recently identified transient cardiomyopathy that is usually associated with emotional or physical stress. Catecholamine surge appears to be central to the mechanism of TTC. TTC in the setting of anaphylaxis is rare. We present a case of a 58-year-old female was referred from an outside hospital after being diagnosed with anaphylaxis. She received 0.3 mg epinephrine intramuscularly and 1 mg intravenously. Upon admission to our hospital, she was complaining of chest pain. EKG done in the outside hospital showed ST elevations in the anterior leads but the EKG done at our hospital was normal. She had to be intubated in view of impending airway obstruction. She was subsequently started on epinephrine infusion in the intensive care unit for hypotension. She was found to have elevated troponins that trended up. An echocardiogram performed on day 3 revealed a left ventricular ejection fraction of 25% and apical hypokinesis suggestive of TTC. Cardiac catheterization was initially deferred in view of a history of dye allergy. A nuclear stress test was done instead that revealed reversible ischemia in anteroseptal regions. Cardiac catheterization was performed eventually with pre-medication that showed a near-normal coronary circulation. A repeat echocardiogram performed 6 weeks after discharge showed normal systolic function.


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