scholarly journals Effects of Cyclosporine on Reperfusion Injury in Patients: A Meta-Analysis of Randomized Controlled Trials

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Kangxing Song ◽  
Shuxia Wang ◽  
Dake Qi

Mitochondrial permeability transition pore (mPTP) opening due to its role in regulating ROS generation contributes to cardiac reperfusion injury. In animals, cyclosporine (cyclosporine A, CsA), an inhibitor of mPTP, has been found to prevent reperfusion injury following acute myocardial infarction. However, the effects of CsA in reperfusion injury in clinical patients are not elucidated. We performed a meta-analysis using published clinical studies and electronic databases. Relevant data were extracted using standardized algorithms and additional data were obtained directly from investigators as indicated. Five randomized controlled blind trials were included in our meta-analysis. The clinical outcomes including infarct size (SMD: −0.41; 95% CI: −0.81, 0.01;P= 0.058), left ventricular ejection fraction (LVEF) (SMD: 0.20; 95% CI: −0.02, 0.42;P= 0.079), troponin I (TnI) (SMD: −0.21; 95% CI: −0.49, 0.07;P= 0.149), creatine kinase (CK) (SMD: −0.32; 95% CI: −0.98, 0.35;P= 0.352), and creatine kinase-MB isoenzyme (CK-MB) (SMD: −0.06; 95% CI: −0.35, 0.23;P= 0.689) suggested that there is no significant difference on cardiac function and injury with or without CsA treatment. Our results indicated that, unlike the positive effects of CsA in animal models, CsA administration may not protect heart from reperfusion injury in clinical patients with myocardial infarction.

2010 ◽  
Vol 8 (1) ◽  
pp. 53-61
Author(s):  
Marcelo Luiz Campos Vieira ◽  
Wercules Antônio Oliveira ◽  
Alexandre Ferreira Cury ◽  
Adriana Cordovil ◽  
Ana Clara Tude Rodrigues ◽  
...  

ABSTRACT Objective: The prognosis of patients with acute myocardial infarction depends on multiple features that can demonstrate myocardial injury degree (such as serum markers of cardiac necrosis), and also on adaptive mechanisms relative to the acute event. The aim of the study was to assess the relation between biochemical and echocardiographic findings from three-dimensional echocardiographic (3D Echo) analysis and echocardiographic two-dimensional (2D Echo) left ventricular ejection fraction in patients with ST-segment elevation acute myocardial infarction, submitted to primary percutaneous treatment. Methods: A prospective study with 2D Echo and 3D Echo of 23 patients (17 males, mean age of 57 ± 13 years) with ST-segment elevation acute myocardial infarction, primarily percutaneously treated (stent). Serum cardiac markers (creatine kinase MB, Troponin I and Myoglobin) and serum brain natriuretic peptide were compared to echocardiographic parameters (volumes, left ventricular ejection fraction and ventricular dyssynchrony index). The statistical analysis was performed using Pearson's correlation coefficient, 95% CI, p < 0.05, linear regression equation and Bland & Altman test. Results: Pearson's correlation coefficient (r)relative to 3D left ventricular ejection fraction: 1- brain natriuretic peptide: r: - 0.7427, p < 0.0001; 2- creatine kinase MB: r: - 0.660, p = 0.001. Left ventricular ejection fraction 2D (r) : 1- brain natriuretic peptide: r: - 0.5478, p = 0.001; 2- creatine kinase MB: r: - 0.4800, p < 0.0277. Other associations were not significant. Conclusions: In this series, it was observed better correlation in regard to serum creatine kinase MB, brain natriuretic peptide and 3D Echo left ventricular ejection fraction, when compared to 2D Echo left ventricular ejection fraction.


1993 ◽  
Vol 39 (6) ◽  
pp. 955-959 ◽  
Author(s):  
P Lechleitner ◽  
N Genser ◽  
J Mair ◽  
J Maier ◽  
E Artner-Dworzak ◽  
...  

Abstract Endothelin is a potent vasoconstrictor of coronary arteries. We measured plasma concentrations of immunoreactive endothelin (irET) in 46 patients with confirmed acute myocardial infarction (AMI). When compared with irET concentrations in healthy individuals who served as controls, irET concentrations in patients were already significantly elevated at the time of admission (P = 0.002) and remained significantly elevated for at least 2 days after AMI (P &lt; 0.01). IrET concentrations peaked 1 h (mean) after admission (8.5 +/- 3.9 ng/L, P = 0.02 compared with values at time of admission). Reperfusion of the infarct-related artery markedly influenced irET release. Before the start of thrombolytic therapy, irET concentration in patients with early reperfusion did not differ significantly from that of those without early reperfusion. However, irET time courses were significantly (P = 0.03 by analysis of variance) different in patients who did and did not have early reperfusion. In the latter, peak irET concentrations correlated closely with the angiographic left ventricular ejection fraction (r = -0.71, P = 0.03), maximum creatine kinase MB mass concentrations (r = 0.69, P = 0.01), and creatine kinase activities (r = 0.59, P = 0.03). Reflow and reversion of myocardial ischemia are associated with a reduced irET release in patients with AMI.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuai Meng ◽  
Yong Zhu ◽  
Kesen Liu ◽  
Ruofei Jia ◽  
Jing Nan ◽  
...  

Abstract Background Left ventricular negative remodelling after ST-segment elevation myocardial infarction (STEMI) is considered as the major cause for the poor prognosis. But the predisposing factors and potential mechanisms of left ventricular negative remodelling after STEMI remain not fully understood. The present research mainly assessed the association between the stress hyperglycaemia ratio (SHR) and left ventricular negative remodelling. Methods We recruited 127 first-time, anterior, and acute STEMI patients in the present study. All enrolled patients were divided into 2 subgroups equally according to the median value of SHR level (1.191). Echocardiography was conducted within 24 h after admission and 6 months post-STEMI to measure left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD). Changes in echocardiography parameters (δLVEF, δLVEDD, δLVESD) were calculated as LVEF, LVEDD, and LVESD at 6 months after infarction minus baseline LVEF, LVEDD and LVESD, respectively. Results In the present study, the mean SHR was 1.22 ± 0.25 and there was significant difference in SHR between the 2 subgroups (1.05 (0.95, 1.11) vs 1.39 (1.28, 1.50), p < 0.0001). The global LVEF at 6 months post-STEMI was significantly higher in the low SHR group than the high SHR group (59.37 ± 7.33 vs 54.03 ± 9.64, p  = 0.001). Additionally, the global LVEDD (49.84 ± 5.10 vs 51.81 ± 5.60, p  = 0.040) and LVESD (33.27 ± 5.03 vs 35.38 ± 6.05, p  = 0.035) at 6 months after STEMI were lower in the low SHR group. Most importantly, after adjusting through multivariable linear regression analysis, SHR remained associated with δLVEF (beta = −9.825, 95% CI −15.168 to −4.481, p  < 0.0001), δLVEDD (beta = 4.879, 95% CI 1.725 to 8.069, p  = 0.003), and δLVESD (beta = 5.079, 95% CI 1.421 to 8.738, p  = 0.007). Conclusions In the present research, we demonstrated for the first time that SHR is significantly correlated with left ventricular negative remodelling after STEMI.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yumei Ye ◽  
Jose R Perez-Polo ◽  
Manjyot K Nanhwan ◽  
Sven Nylander ◽  
Yochai Birnbaum

Background: Clopidogrel (C) and Ticagrelor (T) are P2Y12 ADP receptor antagonists. In addition, ticagrelor inhibits adenosine cell uptake. In PLATO trial T reduced the incidence of the primary composite endpoint myocardial infarction, stroke or cardiovascular death over C in patients with acute coronary syndromes. Previous data show that 7d pretreatment with T limits infarct size (IS) in rats. We compared the effects of C and T, administered just before reperfusion on IS. We also assessed the effect of T and C, administered just before reperfusion and/or 6w oral treatment on cardiac remodeling. Methods: Rats underwent 30min coronary artery ligation. 1) At 25min of ischemia rats received intraperitoneal (IP) vehicle, T (10 or 30mg/kg), or C (12.5mg/kg). Area at risk (AR) was assessed by blue dye and IS by TTC staining 24h after reperfusion. 2) Rats received vehicle without (sham) or with (control) coronary ischemia, T (30mg/kg) IP (TIP), T (300mg/kg/d) oral for 6w, started a day after reperfusion (TPO), TIP+PO (TIPPO), or C (12.5mg/kg IP +62.5mg/kg/d PO for 6w). LV dimensions and function was assessed by echo at 6w. Results: 1) AR was comparable among groups. IS was 45.3±1.7% of the AR in the control group. T10 (31.5±1.8%; p=0.001) and T30 (21.4±2.6% p<0.001) significantly reduced IS, whereas C (42.4±2.6%) had no effect. Platelet aggregation in the controls was 64.7±1.3% and was comparable in T30 (24.9±1.8%) and C (23.2±1.8%) at 2h post reperfusion. T30 increased Akt, eNOS and ER1/2 phosphorylation 4h after reperfusion, whereas C had no effect. 2) Platelet aggregation at 1w oral treatment was 59.7±3.2% in the control group and was comparable in TIPPO (18.1±1.3%) and C (17.4±0.7%). Left ventricular ejection fraction was 77.6±0.9%*, 44.8±3.5%, 69.5±1.6%*, 69.2±1.0%*, 76.3±1.2%*, and 37.4±3.7% in the sham, vehicle, TIP, TPO, TIPPO and C treated group, respectively (*p<0.001 vs. vehicle). Left ventricular diameters at diastole and systole showed the same pattern. Conclusions: T, but not C, administered just before reperfusion protects against reperfusion injury. Oral T (in combination or not with acute treatment just before reperfusion) treatment for 6w improves heart function. C, despite achieving similar degree of platelet inhibition had no effect on remodeling.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Stephanie Wu ◽  
Marie Lauzon ◽  
Jenna Maughan ◽  
Leslee J Shaw ◽  
Sheryl F Kelsey ◽  
...  

Background: Relatively high left ventricular ejection fraction (EF) (>65%) in women was recently associated with higher all-cause mortality over 6 years follow-up in the CONFIRM study. We sought to evaluate high EF and major adverse cardiovascular events (MACE) in the Women’s Ischemia Syndrome Evaluation (WISE) study. Methods: The WISE original cohort (enrolled 1996-2000) is a multicenter prospective study of women with suspected ischemic heart disease undergoing clinically indicated invasive coronary angiography. We investigated the relationship between high (>65%) and normal (55-65%) EF and MACE, defined as all-cause death, nonfatal myocardial infarction (MI), stroke and heart failure (HF) hospitalization using Kaplan Meier (KM) and regression analyses. Results: A total of 653 women were included (298 high and 355 normal EF). Mean age was 58±11 years and mean EF was 68±7%. There was no significant difference in MACE by EF group over a 10-year follow-up period (log rank p=0.54, Figure ). When patients were stratified by the presence of obstructive CAD, MACE rates remained similar between high and normal EF. High EF was not associated with stroke or HF but had a lower MI risk (log rank p=0.03, Table ). EF was not associated with MACE in a multivariable regression model. Conclusions: Among women presenting with evidence of ischemia, there was no significant difference in MACE between high and normal EF groups. High EF was associated with a lower risk of myocardial infarction as an individual component of MACE.


Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000810 ◽  
Author(s):  
Ivo M van Dongen ◽  
Joëlle Elias ◽  
K Gert van Houwelingen ◽  
Pierfrancesco Agostoni ◽  
Bimmer E P M Claessen ◽  
...  

ObjectiveThe impact on cardiac function of collaterals towards a concomitant chronic total coronary occlusion (CTO) in patients with ST-elevation myocardial infarction (STEMI) has not been investigated yet. Therefore, we have evaluated the impact of well-developed collaterals compared with poorly developed collaterals to a concomitant CTO in STEMI.Methods and resultsIn the EXPLORE trial, patients with STEMI and a concomitant CTO were randomised to either CTO percutaneous coronary intervention (PCI) or no-CTO PCI. Collateral grades were scored angiographically using the Rentrop grade classification. Left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) at 4 months were measured using cardiac magnetic resonance imaging. Well-developed collaterals (Rentrop grades 2–3) to the CTO were present in 162 (54%) patients; these patients had a significantly higher LVEF at 4 months (46.2±11.4% vs 42.1±12.7%, p=0.004) as well as a trend for a lower LVEDV (208.2±55.7 mL vs 222.6±68.5 mL, p=0.054) when compared with patients with poorly developed collaterals to the CTO. There was no significant difference in the total amount of scar in the two groups. Event rates were statistically comparable between patients with well-developed collaterals and poorly developed collaterals to the CTO at long-term follow-up.ConclusionsIn patients with STEMI and a concomitant CTO, the presence of well-developed collaterals to a concomitant CTO is associated with a better LVEF at 4 months. However, this effect on LVEF did not translate into improvement in clinical outcome. Therefore, the presence of well-developed collaterals is important, but should not solely guide in the clinical decision-making process regarding any additional revascularisation of a concomitant CTO in patients with STEMI.Clinical trial registrationNTR1108.


Circulation ◽  
2020 ◽  
Vol 142 (15) ◽  
pp. 1408-1421 ◽  
Author(s):  
Mark Y. Chan ◽  
Motakis Efthymios ◽  
Sock Hwee Tan ◽  
John W. Pickering ◽  
Richard Troughton ◽  
...  

Background: Heart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery. Methods: We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.9 years. We then correlated plasma proteins with left ventricular ejection fraction measured at 4 months post-MI and identified proteins potentially coregulated in post-MI HF using weighted gene co-expression network analysis. A Singapore cohort (IMMACULATE [Improving Outcomes in Myocardial Infarction through Reversal of Cardiac Remodelling]) of 223 patients post-MI, of which 33 patients were hospitalized for HF (median follow-up, 2.0 years), was used for further candidate enrichment of plasma proteins by using Fisher meta-analysis, resampling-based statistical testing, and machine learning. We then cross-referenced differentially expressed proteins with their differentially expressed genes from single-cell transcriptomes of nonmyocyte cardiac cells isolated from a murine MI model, and single-cell and single-nucleus transcriptomes of cardiac myocytes from murine HF models and human patients with HF. Results: In the CDCS cohort, 212 differentially expressed plasma proteins were significantly associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at 4 months post-MI. Weighted gene co-expression network analysis prioritized 63 of the 212 proteins that demonstrated significantly higher correlations among patients who developed post-MI HF in comparison with event-free controls (data set 1). Cross-cohort meta-analysis of the IMMACULATE cohort identified 36 plasma proteins associated with post-MI HF (data set 2), whereas single-cell transcriptomes identified 15 gene-protein candidates (data set 3). The majority of prioritized proteins were of matricellular origin. The 6 most highly enriched proteins that were common to all 3 data sets included well-established biomarkers of post-MI HF: N-terminal B-type natriuretic peptide and troponin T, and newly emergent biomarkers, angiopoietin-2, thrombospondin-2, latent transforming growth factor-β binding protein-4, and follistatin-related protein-3, as well. Conclusions: Large-scale human plasma proteomics, cross-referenced to unbiased cardiac transcriptomics at single-cell resolution, prioritized protein candidates associated with post-MI HF for further mechanistic and clinical validation.


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