scholarly journals Protective Mechanism of Trimetazidine in Myocardial Cells in Myocardial Infarction Rats through ERK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhenjun Wu ◽  
Lihua Yu ◽  
Xinyue Li ◽  
Xuewen Li

Objective. To study the protective effect of trimetazidine on myocardial cells in rats with myocardial infarction and explore its effect on ERK signaling pathway. Methods. 40 SD rats were randomly divided into the sham operation group, model group, low-dose group, and high-dose group (intra-abdominal injection of trimetazidine 5 mg/kg and 10 mg/kg, respectively), construction of rat myocardial infarction model by coronary artery left anterior descending artery ligation. 7 days after surgery, the survival rate and cardiac function of each group of rats were recorded. The myocardial infarct size was detected by TTC staining. The apoptosis level of rat cardiomyocytes was detected by TUNEL staining. The content of ROS in rat cardiomyocytes was detected by DCFH-DA. Western-blot was used to detection of Caspase-3, Bcl-2/Bax, and ERK signaling pathway-related proteins in myocardial tissue. Results. Compared with the model group, the survival rate of the rats in the low-dose group and the high-dose group was significantly increased ( P < 0.01 ), the cardiac function was significantly improved ( P < 0.01 ), the myocardial infarct size was significantly decreased ( P < 0.01 ), the level of apoptosis was significantly decreased ( P < 0.01 ), the content of ROS in cardiomyocytes was significantly decreased ( P < 0.01 ), the protein expression of Caspase-3 and NF-κB in cardiomyocytes was significantly decreased ( P < 0.01 ), and the expression of Bcl-2/Bax and p-ERK were significantly increased ( P < 0.01 ). Conclusion. Trimetazidine can activate ERK signaling pathway in cardiomyocytes of rats with myocardial infarction, increase the expression of p-ERK, decrease the content of ROS in cardiomyocytes, decrease the expression of apoptotic proteins, reduce myocardial infarct size, improve cardiac function, and increase myocardial function.

Author(s):  
Alexander B Veitinger ◽  
Audrey Komguem ◽  
Lena Assling-Simon ◽  
Martina Heep ◽  
Julia Schipke ◽  
...  

Abstract OBJECTIVES Esmolol-based cardioplegic arrest offers better cardioprotection than crystalloid cardioplegia but has been compared experimentally with blood cardioplegia only once. We investigated the influence of esmolol crystalloid cardioplegia (ECCP), esmolol blood cardioplegia (EBCP) and Calafiore blood cardioplegia (Cala) on cardiac function, metabolism and infarct size in non-infarcted and infarcted isolated rat hearts. METHODS Two studies were performed: (i) the hearts were subjected to a 90-min cardioplegic arrest with ECCP, EBCP or Cala and (ii) a regional myocardial infarction was created 30 min before a 90-min cardioplegic arrest. Left ventricular peak developed pressure (LVpdP), velocity of contractility (dLVP/dtmax), velocity of relaxation over time (dLVP/dtmin), heart rate and coronary flow were recorded. In addition, the metabolic parameters were analysed. The infarct size was determined by planimetry, and the myocardial damage was determined by electron microscopy. RESULTS In non-infarcted hearts, cardiac function was better preserved with ECCP than with EBCP or Cala relative to baseline values (LVpdP: 100 ± 28% vs 86 ± 11% vs 57 ± 7%; P = 0.002). Infarcted hearts showed similar haemodynamic recovery for ECCP, EBCP and Cala (LVpdP: 85 ± 46% vs 89 ± 55% vs 56 ± 26%; P = 0.30). The lactate production with EBCP was lower than with ECCP (0.6 ± 0.7 vs 1.4 ± 0.5 μmol/min; P = 0.017). The myocardial infarct size and (ECCP vs EBCP vs Cala: 16 ± 7% vs 15 ± 9% vs 24 ± 13%; P = 0.21) the ultrastructural preservation was similar in all groups. CONCLUSIONS In non-infarcted rat hearts, esmolol-based cardioplegia, particularly ECCP, offers better myocardial protection than Calafiore. After an acute myocardial infarction, cardioprotection with esmolol-based cardioplegia is similar to that with Calafiore.


2021 ◽  
Author(s):  
Qingxin Tian ◽  
Jianlong Liu ◽  
Qin Chen ◽  
Mingxiao Zhang

Abstract Objectives: To determine the effect of polyethyleneimine/sodium alginate composite nano-gel (AG/PEI-VX765NGs) coated with VX765 on cardiac function in rats with myocardial infarction (MI). Methods: VX765-polyethyleneimine nano-microspheres (PEI-VX765 NP) were encapsulated by sodium alginate (AG) nanogel (NGs) to construct AG/PEI-VX765 NGs. The morphological observation was performed under scanning electron microscope (SEM). The viability was evaluated by using CCK-8 assay in vitro. Then, 24 male SPF Sprague-Dawley rats were randomly divided into 4 groups: Sham, MI, PEI-VX765NP, and AG/PEI-VX765NGs. After 28 days, rats in each group were subjected to assessment of cardiac function by echocardiography. The myocardial infarct size was evaluated by TTC test, and the differences in cardiac fibrosis and cardiomyocyte apoptosis between groups were analyzed by histological methods. Results: The prepared NGs shows a porous structure, while PEI-VX765 NP is uniformly distributed in the AG NGs samples. AG/PEI-VX765 NGs with a concentration of VX765 (range: 0-1000 μM) displayed no significant toxicity to cells. Meanwhile, we observed a relatively more persistent release of VX765 from AG/PEI-VX765 NGs compared with PEI-VX765. LVIDs and LVIDd in both PEI-VX765 and AG/PEI-VX765NGs groups were significantly smaller than those in MI group, while ejection fraction (EF) and short-axis shortening rate (FS) were markedly increased in the above-mentioned two groups. Compared with MI group, PEI-VX765 and AG/PEI-VX765NGs groups exhibited a significant reduction in the infarct size, degree of fibrosis, and the rate of TUNEL positive cells. Conclusion: AG/PEI-VX765NGs can significantly improve the cardiac function of rats with MI.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ya-Ru Bao ◽  
Wen-Yi Jiang ◽  
Jia-Yu Yu ◽  
Jing-Wei Chen ◽  
Guo-Xing Zhang

Huangqi Jianzhong Tang (HQJZT) is a traditional Chinese herbal formula consisting of seven different herbs: Radix Astragali, Radix Paeoniae Alba, Ramulus Cinnamomi, Fructus Jujubae, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Rhizoma Zingiberis Recens, and Saccharum Granorum. The present study aims to evaluate the possible effects of HQJZT on cardiac function in acute myocardial infarction (AMI) and related mechanism. AMI model was established by ligation of the left anterior descending coronary artery followed by one-week HQJZT treatment. Survival rate was calculated. Rat heart function was assessed by heart performance analysis system. 5-Triphenyltetrazolium chloride (TTC) staining was used to observe myocardial infarct size. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and western blot were applied to evaluate tissue apoptotic level. Treatment with high dose of HQJZT improved cardiac function, reduced infarct size, number of apoptotic cells and expression of apoptotic proteins, Bax (a proapoptotic protein), and increased expression of antiapoptotic protein, Bcl2. However, enalapril (an angiotensin-converting enzyme inhibitor) treatment did not show marked improvement of these parameters. Our present data suggest that HQJZT has potential therapeutic effects to improve cardiac function by regulation of apoptotic signaling pathway.


2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P1309-P1309
Author(s):  
C. P. H. Lexis ◽  
W. G. Wieringa ◽  
B. Hiemstra ◽  
V. M. Van Deursen ◽  
E. Lipsic ◽  
...  

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Shohei Sumi ◽  
Masamitsu Iwasa ◽  
Hiroyuki Kobayashi ◽  
Shinji Yasuda ◽  
Takahiko Yamaki ◽  
...  

It has been reported that granulocyte-colony-stimulating factor(G-CSF) improves cardiac function after myocardial infarction (MI). However, its direct effect on the myocardium and its signaling pathway remain unclear. We examined the acute beneficial effect of G-CSF on myocardial infarct size and its precise mechanisms in a rabbit model of myocardial infarction. In 80 Japanese white rabbits, MI was induced by 30 min of ischemia and 48 hours of reperfusion. Rabbits were intravenously injected with 10 μg/kg of G-CSF (G-CSF group, n=10) or saline (control group, n=10) immediately after reperfusion. The G-CSF+5HD group (n=10) was injected with 5-HD(5-hydroxydecanoate, a mitochondrial KATP channel blocker) 5 min before G-CSF injection. The G-CSF +wortmaninn group (n=10) was injected wortmaninn (0.6mg/kg) 5 min before G-CSF injection. G-CSF+L-NAME group (n=10) was injected with L-NAME (10mg/kg) 5 min before G-CSF injection. The 5HD alone (n=10), wortmannin alone (n=10), L-NAME alone (n=10) groups were respectively injected 5HD, wortmannin and L-NAME immediately after reperfusion. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot analysis was performed to examine the Akt and phospho-Akt and phospho-eNOS in the ischemic myocardium at 48 hours of reperfusion. The infarct size was significantly smaller in the G-CSF group (26.7±2.7%) than in the control group (42.3±4.6%). The infarct size-reducing effect of G-CSF was completely blocked by 5-HD (42.5±1.66%), wortmaninn(44.7±4.81) and L-NAME (42.1±4.2%). Wortmannin, L-NAME or 5HD alone did not affect the infarct size. Western blotting showed higher expression of phospho-Akt and phosho-eNOS in the infarct area in the G-CSF group than in the control group. G-CSF administered immediately after reperfusion reduces myocardial infarct size via activation of PI3K, Akt, eNOS and opening the mitochondrial KATP channels.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Marie Sophie L de Koning ◽  
B. D Westenbrink ◽  
Solmaz Assa ◽  
Dirk J van Veldhuisen ◽  
Robin P Dullaart ◽  
...  

Background: Circulating ketone bodies (KB) are increased in patients with heart failure, corresponding with increased utilization of KB as a cardiac fuel. Whether circulating KB are increased in patients presenting with ST-elevation myocardial infarction (STEMI) and whether this is associated with infarct size is unknown. Methods: KB were measured in 379 non-diabetic participants of the Glycometabolic Intervention as Adjunct to Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction (GIPS) III trial (Clinicaltrial.gov Identifier: NCT01217307). Non-fasting plasma concentrations of the KB beta-hydroxybutyrate, acetoacetate, acetone were measured at presentation, 24 hours and 4 months after STEMI presentation using nuclear magnetic resonance spectroscopy. Associations of circulating KB with myocardial infarct size and left ventricular ejection fraction (both detected with MRI at 4 months after STEMI) were determined using multivariable linear regression analyses. Results: Circulating KB were higher at baseline (total KB 520 [315-997](median [IQR], μmol/L), compared to 206 [174-246] at 24 hours and 166 [143-201] at 4 months ( P <0.001 for all)). KB at 24 hours were positively associated with enzymatic infarct size, HbA1C and beta-blocker use. KB at 24 hours were independently associated with MRI outcomes at 4 months. Higher KB was associated with larger myocardial infarct size (total KB: standardized β=0.17, 95%-confidence interval (CI) (0.04-0.31), P =0.012) and lower ejection fraction (standardized β=-0.15, 95%-CI (-0.29- -0.009), P =0.037). Conclusion: Circulating KB are increased in patients with STEMI and are independently associated with myocardial infarct size and left ventricular function after 4 months of follow-up. The increase in circulating KB may reflect maladaptive changes of myocardial metabolism during the acute phase.


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