scholarly journals Shexiang Baoxin Pill for Acute Myocardial Infarction: Clinical Evidence and Molecular Mechanism of Antioxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jianbo Guo ◽  
Zongshi Qin ◽  
Qingyong He ◽  
Tung Leong Fong ◽  
Ngai Chung Lau ◽  
...  

Acute myocardial infarction (AMI) has been a preclinical and clinical concern due to high hospitalization rate and mortality. This study was aimed at evaluating the effectiveness and safety of Shexiang Baoxin Pill (SBP) for AMI and exploring the possible mechanism of oxidative stress. Six databases were searched on March 26, 2021. Twenty-four studies were included and accessed by the RoB 2.0 or SYRCLE tool. Compared with routine treatment (RT), SBP showed the effectiveness in the clinical efficacy ( RR = 1.15 , 95% CI [1.06, 1.25]), left ventricular ejection fraction (LVEF) ( SMD = 0.73 , 95% CI [0.62, 0.95]), glutathione (GSH) ( SMD = 2.07 , 95% CI [1.51, 2.64]), superoxide dismutase (SOD) ( SMD = 0.92 , 95% CI [0.58, 1.26]), malondialdehyde (MDA) ( SMD = − 4.23 , 95% CI [-5.80, -2.66]), creatine kinase-myocardial band (CK-MB) ( SMD = − 4.98 , 95% CI [-5.64, -4.33]), cardiac troponin I (cTnI) ( SMD = − 2.17 , 95% CI [-2.57, -1.76]), high-sensitivity C-reactive protein (Hs-CRP) ( SMD = − 1.34 , 95% CI [-1.56, -1.12]), interleukin-6 (IL-6) ( SMD = − 0.99 , 95% CI [-1.26, -0.71]), triglycerides (TG) ( SMD = − 0.52 , 95% CI [-0.83, -0.22]), flow-mediated dilation (FMD) ( SMD = 1.39 , 95% CI [1.06, 1.72]), von Willebrand Factor (vWF) ( SMD = − 1.77 , 95% CI [-2.39, -1.15]), nitric oxide (NO) ( SMD = 0.89 , 95% CI [0.65, 1.13]), and recurrent rate ( RR = 0.30 , 95% CI [0.15, 0.59]). But SBP adjunctive to RT plus PCI had no improvements in almost pooled outcomes except for the Hs-CRP ( SMD = − 1.19 , 95% CI [-1.44, -0.94]) and TG ( SMD = − 0.25 , 95% CI [-0.48, -0.02]). Laboratory findings showed that SBP enhanced the endothelial nitric oxide synthase (eNOS) activity and regulated laboratory indexes especially for homocysteine. In conclusion, SBP has adjunctive effects on AMI via the mechanism of antioxidative stress. The current evidence supports the use of SBP for mild and moderate AMI patients.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Von Lewinski ◽  
B Merkely ◽  
I Buysschaert ◽  
R.A Schatz ◽  
G.G Nagy ◽  
...  

Abstract Background Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Mobilization of stem cells and homing within the infarcted area have been identified as the key mechanisms for successful treatment. Application of granulocyte-colony stimulating factor (G-CSF) is the least invasive way to mobilize stem cells while DDP4-inhibitor facilitates homing via stromal cell-derived factor 1 alpha (SDF-1α). Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model. Purpose We initiated a phase II, multicenter, randomized, placebo-controlled efficacy and safety study (N=140) analyzing the effect of combined application of G-CSF and dutogliptin, a small molecule DPP-IV-inhibitor for subcutaneous use after acute myocardial infarction. Methods The primary objective of the study is to evaluate the safety and tolerability of dutogliptin (14 days) in combination with filgrastim (5 days) in patients with STEMI (EF <45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect >3.8% improvement in left ventricular ejection fraction (LV-EF). 140 subjects will be randomized to filgrastim plus dutogliptin or matching placebos. Results Baseline characteristics of the first 26 patients randomized (24 treated) in this trial reveal a majority of male patients (70.8%) and a medium age of 58.4 years (37 to 84). During the 2-week active treatment period, 35 adverse events occurred in 13 patients, with 4 rated as serious (hospitalization due to pneumonia N=3, hospitalization due to acute myocardial infarction N=1), and 1 adverse event was rated as severe (fatal pneumonia), 9 moderate, and 25 as mild. 6 adverse events were considered possibly related to the study medication, including cases of increased hepatic enzymes (N=3), nausea (N=1), subcutaneous node/suffusion (N=1) and syncope (N=1). Conclusions Our data demonstrate that the combined application of dutogliptin and G-CSF appears to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This research is funded by the sponsor RECARDIO, Inc., 1 Market Street San Francisco, CA 94150, USA. RECARDIO Inc. is funding the complete study. The Scientific Board of RECARDIO designed the study. Data Collection is at the participating sites. Interpretation of the data by the Scientific Board and Manuscript written by the authors and approved by the Sponsor


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
YeeKyoung KO ◽  
Seungjae JOO ◽  
Jong Wook Beom ◽  
Jae-Geun Lee ◽  
Joon-Hyouk CHOI ◽  
...  

Introduction: In the era of the initial optimal interventional and medical therapy for acute myocardial infarction (AMI), a number of patients with mid-range left ventricular ejection fraction (40% <EF<50%) becomes increasing. However, the long-term optimal medical therapy for these patients has been rarely studied. Aims: This observational study aimed to investigate the association between the medical therapy with beta-blockers or inhibitors of renin-angiotensin system (RAS) and clinical outcomes in patients with mid-range EF after AMI. Methods: Among 13,624 patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), propensity-score matched patients who survived the initial attack and had mid-range EF were selected according to beta-blocker or RAS inhibitor therapy at discharge. Results: Patients with beta-blockers showed significantly lower 1-year cardiac death (2.4 vs. 5.2/100 patient-year; hazard ratio [HR] 0.46; 95% confidence interval [CI] 0.22-0.98; P =0.045) and MI (1.7 vs. 4.0/100 patient-year; HR 0.41; 95% CI 0.18-0.95; P =0.037). On the other hand, RAS inhibitors were associated with lower 1-year re-hospitalization due to heart failure (2.8 vs. 5.5/100 patient-year; HR 0.54; 95% CI 0.31-0.92; P =0.024), and no significant interaction with classes of RAS inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) was observed ( P for interaction=0.332). Conclusions: Beta-blockers or RAS inhibitors at discharge were associated with better 1-year clinical outcomes in patients with mid-range EF after AMI.


2019 ◽  
Vol 26 (4) ◽  
pp. 32-43
Author(s):  
O. M. Parkhomenko ◽  
Ya. M. Lutay ◽  
O. I. Irkin ◽  
D. O. Bilyi ◽  
A. O. Stepura ◽  
...  

We retrospectively and prospectively studied 835 patients with acute myocardial infarction (AMI) under the age of 45 and older. Depending on age, patients were divided into two groups: < 45 years and ≥ 45 years. In 189 patients under 45 years of age, the main risk factors leading to the development of ST-elevation myocardial infarction were male sex (OR 6.58; 95 % CI (2.64–16.41), smoking (OR 2.02; 95 % CI (1.44–2.82) and family history of premature coronary artery disease (OR 1.75; 95 % CI (1.21–2.54). According to coronary angiography, AMI patients under 45 years of age in most cases showed no hemodynamically significant coronary vessels damage and had a different course of AMI caused by other reasons – aneurysms of the coronary arteries, muscle bridges, coronary spasm, spontaneous dissections. It was found that 10 % of young patients who did not have obstructive lesions of coronary vessels, according to magnetic resonance imaging (MRI) had focal myocarditis. However, it is noted that in patients under 45 years of age, the presence of familial hypercholesterolemia (FH) may affect the development of AMI. Thus, according to the DLCNS criteria, FH was more frequently reported in young patients than in patients older than 45 years (7.34 % vs 1.32 % (p<0.05)). Hospital course of AMI in young adults was more favorable, with fewer complications. Data from studies of flow-dependent vasodilation have shown that young patients have worse endothelial function on the 1st day of AMI (p=0.043), but better recovery of it in the dynamics of observation. However, in young patients, early (day 7, p=0.029) and late (day 90, p=0.041) left ventricular dilatation was more commonly reported compared with older patients. According to the MRI data on day 1 and in the dynamics (90 days), it was found that, despite the higher prevalence of AMI, young patients have better recovery of contractile myocardial function. The arrhythmogenic substrate (according to late ventricular potential) for life-threatening arrhythmias was more commonly recorded in the older age group at the beginning of the development of AMI, but it was detected with the same frequency in both groups during prolonged observation (6–12 months). Despite better survival and fewer complications during long-term follow-up (4.9 years on average), the greatest impact on the development of the combined endpoint (cardiovascular death / recurrent myocardial infarction / stroke) and death from any cause was made by the patients’ age up to 35 years (best prognosis), concomitant hypertension (worsens prognosis) and low left ventricular ejection fraction (increases complications). The study indicates the possibility of implementing a secondary prevention system in AMI patients of young age through careful (active) observation and control of adherence to treatment and the adequacy of its implementation.


2020 ◽  
Vol 21 (13) ◽  
pp. 4591
Author(s):  
Denise Traxler ◽  
Andreas Spannbauer ◽  
Patrick Einzinger ◽  
Julia Mester-Tonczar ◽  
Dominika Lukovic ◽  
...  

Clusterin exerts anti-inflammatory, cytoprotective and anti-apoptotic effects. Both an increase and decrease of clusterin in acute myocardial infarction (AMI) has been reported. We aimed to clarify the role of clusterin as a systemic biomarker in AMI. AMI was induced by percutaneous left anterior artery (LAD) occlusion for 90 min followed by reperfusion in 24 pigs. Contrast ventriculography was performed after reperfusion to assess left ventricular ejection fraction (LVEF), left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) and additional cMRI + late enhancement to measure infarct size and LV functions at day 3 and week 6 post-MI. Blood samples were collected at prespecified timepoints. Plasma clusterin and other biomarkers (cTnT, NT-proBNP, neprilysin, NGAL, ET-1, osteopontin, miR21, miR29) were measured by ELISA and qPCR. Gene expression profiles of infarcted and remote region 3 h (n = 5) and 3 days (n = 5) after AMI onset were analysed by RNA-sequencing. AMI led to an increase in LVEDV and LVESV during 6-week, with concomitant elevation of NT-proBNP 3-weeks after AMI. Plasma clusterin levels were increased immediately after AMI and returned to normal levels until 3-weeks. Plasma NGAL, ET-1 and miR29 was significantly elevated at 3 weeks follow-up, miR21 increased after reperfusion and at 3 weeks post-AMI, while circulating neprilysin levels did not change. Elevated plasma clusterin levels 120 min after AMI onset suggest that clusterin might be an additional early biomarker of myocardial ischemia.


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