scholarly journals Cardioprotective effects of Ginsenoside compound-Mc1 and Dendrobium Nobile Lindl against myocardial infarction in an aged rat model: Involvement of TLR4/NF-κB signaling pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110005
Author(s):  
Yongle Sun ◽  
Jing Geng ◽  
Deyu Wang
Keyword(s):  
Myocardial Infarction ◽  
Combination Therapy ◽  
Infarct Size ◽  
Signaling Pathway ◽  
Left Ventricular ◽  
Male Rats ◽  
Dendrobium Nobile ◽  
Tnf Α ◽  
Cardioprotective Effects ◽  
Dendrobium Nobile Lindl

Aging is the crucial co-morbidity that prevents the full cardioprotection against myocardial ischemia/reperfusion (I/R) injury. Combination therapy as a promising strategy may overcome this clinical problem. This study aimed to investigate the cardioprotective effects of Ginsenoside compound-Mc1 (GMc1) and Dendrobium Nobile Lindl (DNL) in myocardial I/R injury and explore the involvement of the TLR4/NF-κB signaling pathway in aged rats. In vivo I/R injury and myocardial infarction was established by temporary coronary ligation in 22–24 months’ old Sprague Dawley male rats. GMc1 (10 mg/kg) and DNL (80 mg/kg) were administered intraperitoneally for 4 weeks and orally for 14 days, respectively, before I/R injury. Infarct size was measured through triphenyl-tetrazolium-chloride staining. ELISA assay was conducted to quantify the levels of cardiotroponin, and myocardial content of TNF-α and glutathione. Western blotting was employed to detect the expression of TLR4/MyD88/NF-κB proteins. GMc1 and DNL significantly reduced the infarct size to a similar extent ( p < 0.05) but their combined effect was greater than individual ones ( p < 0.01). Combination therapy significantly restored the left ventricular end-diastolic and developed pressures at the end of reperfusion as compared with the untreated group ( p < 0.01). Although the GMc1 and DNL reduced the levels of inflammatory cytokine TNF-α and increased the contents of antioxidant glutathione significantly, their individual effects on the reduction of protein expression of TLR4/MyD88/NF-κB pathway were not consistent. However, their combination could significantly reduce all parameters of this inflammatory pathway as compared to untreated I/R rats ( p < 0.001). Therefore, the combined treatment with GMc1 and DNL increased the potency of each intervention in protecting the aged hearts against I/R injury. Reduction in the activity of the TLR4/MyD88/NF-κB signaling pathway and subsequent modulation of the activity of inflammatory cytokines and endogenous antioxidants play an important role in this cardioprotection.

Preinfarction Angina and Improved Reperfusion of the Infarct-related Artery

1999 ◽  
Vol 82 (S 01) ◽  
pp. 68-72 ◽  
Author(s):  
Alessandro Sciahbasi ◽  
Eugenia De Marco ◽  
Attilio Maseri ◽  
Felicita Andreotti
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Early Reperfusion ◽  
Vast Number ◽  
Beneficial Effects ◽  
Infarct Related Artery ◽  
Cardioprotective Effects ◽  
Collateral Vessels

SummaryPreinfarction angina and early reperfusion of the infarct-related artery are major determinants of reduced infarct-size in patients with acute myocardial infarction. The beneficial effects of preinfarction angina on infarct size have been attributed to the development of collateral vessels and/or to post-ischemic myocardial protection. However, recently, a relation has been found between prodromal angina, faster coronary recanalization, and smaller infarcts in patients treated with rt-PA: those with preinfarction angina showed earlier reperfusion (p = 0.006) and a 50% reduction of CKMB-estimated infarct-size (p = 0.009) compared to patients without preinfarction angina. This intriguing observation is consistent with a subsequent observation of higher coronary recanalization rates following thrombolysis in patients with prodromal preinfarction angina compared to patients without antecedent angina. Recent findings in dogs show an enhanced spontaneous lysis of plateletrich coronary thrombi with ischemic preconditioning, which is prevented by adenosine blockade, suggesting an antithrom-botic effect of ischemic metabolites. Understanding the mechanisms responsible for earlier and enhanced coronary recanalization in patients with preinfarction angina may open the way to new reperfusion strategies.A vast number of studies, globally involving ≈17,000 patients with acute myocardial infarction, have unequivocally shown that an infarction preceded by angina evolves into a smaller area of necrosis compared to an infarct not preceded by angina (Table 1) (1). So far, preinfarction angina has been thought to have cardioprotective effects mainly through two mechanisms: collateral perfusion of the infarctzone (2-4), and ischemic preconditioning of the myocardium (5-7). Here we discuss a further mechanism of protection represented by improved reperfusion of the infarct-related artery.

Implication of anti-angiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Marcos Garces ◽  
C Rios-Navarro ◽  
L Hueso ◽  
A Diaz ◽  
C Bonanad ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Adjuvant Therapy ◽  
Ejection Fraction ◽  
Infarct Size ◽  
Systolic Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Coronary Reperfusion ◽  
Ventricular Ejection Fraction

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).

scholarly journals The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats

Open Medicine ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. 047-057
Author(s):  
Lei Gong ◽  
Xuyang Wang ◽  
Jinyu Pan ◽  
Mingjun Zhang ◽  
Dian Liu ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Mtor Signaling ◽  
Maximal Rate ◽  
H9c2 Cells ◽  
Mtor Signaling Pathway ◽  
Cardioprotective Effects

AbstractObjectiveThe purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism.MethodsSprague-Dawley (SD) rats (n = 25) were divided into five groups randomly: (1) Sham, (2) I/R, (3) I/R + RSV (10 mg/kg), (4) IR + DGZ (1 mg/kg), and (5) I/R + RSV (10 mg/kg) + DGZ (1 mg/kg). The I/R model was induced with 30 min of left anterior descending occlusion followed by 120 min of reperfusion.ResultsIn vivo pretreatment with RSV and DGZ, respectively, showed a significant reduction of infarction size, a significant increase in the levels of left ventricular systolic pressure, and maximal rate increase in left ventricular pressure (+dp/dtmax), decrease in the levels of left ventricular end-diastolic pressure (LVEDP), maximal rate of decrease of left ventricular pressure (−dp/dtmax) and activity of cardiac enzymes of creatine kinase (CK), creatine kinase MB isoenzymes (CK-MB), and hyper-tensive cardiac troponin I compared with the I/R group. H9C2 cells were exposed to hypoxia/reoxygenation to simulate an I/R model. In vitro administration of 25 µM RSV and 50 µM DGZ significantly enhanced cell viability, upregulated the expression levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2, whereas it downregulated cleaved-caspase3, Bax. TUNEL assay indicated that pretreatment with RSV and DGZ decreased the apoptosis of H9C2 cells.ConclusionThe combination of RSV and DGZ significantly enhances the cardioprotective effects compared with RSV or DGZ alone. RSV and DGZ have the potential cardioprotective effects against I/R injury by activating the PI3K/AKt/mTOR signaling pathway.

Cardioprotection with esmolol-based cardioplegia for non-infarcted and infarcted rat hearts

2021 ◽  
Author(s):  
Alexander B Veitinger ◽  
Audrey Komguem ◽  
Lena Assling-Simon ◽  
Martina Heep ◽  
Julia Schipke ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Lactate Production ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Cardioplegic Arrest ◽  
Blood Cardioplegia ◽  
Rat Hearts

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.

Abstract P210: Central Blockade Of Tumor Necrosis Factor-Á-Converting Enzyme (tace) Ameliorates Neuroinflammation, Sympathetic Excitation And Cardiac Dysfunction In Heart Failure Rat

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yang Yu ◽  
Baojian Xue ◽  
Hanzeng Li ◽  
Qing Chen ◽  
Mingxuan Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Cardiac Dysfunction ◽  
Tumor Necrosis ◽  
Left Ventricular ◽  
Male Rats ◽  
Tnf Α ◽  
Necrosis Factor

TACE is a key metalloprotease involved in ectodomain shedding of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-α. We previously reported that TACE-mediated production of TNF-α in the hypothalamic paraventricular nucleus (PVN) contributes to the sympathetic excitation in heart failure (HF). Additionally, the upregulated TGF-α in the PVN transactivates the epidermal growth factor receptor (EGFR) to activate extracellular signal-regulated kinase (ERK) 1/2 in HF. Here we sought to determine whether central inhibition of TACE attenuates neuroinflammation and prevents the progress of HF. Male rats underwent coronary artery ligation to induce HF or sham surgery (Sham). These rats were treated with bilateral PVN microinjection of a TACE siRNA or control siRNA while some rats received a 4-week intracerebroventricular (ICV) infusion of TACE inhibitor TAPI-0 or vehicle. Compared with Sham rats, HF rats treated with control siRNA, had higher (*P<0.05) levels of TNF-α (7.88±1.32* vs 2.77±0.98 pg/mL) and TGF-α (28.27±2.76* vs 11.62±2.48 pg/mL) in cerebrospinal fluid, and increased mRNA expression of TACE (2.53±0.30* vs 1.04±0.12), TNF-α (3.43±0.55* vs 1.03±0.11), TNF-α receptor 1 (2.32±0.27* vs 1.07±0.19), cyclooxygenase-2 (2.96±0.31* vs 1.10±0.19) and TGF-α (2.68±0.41* vs 1.06±0.14) in the PVN, but these levels were markedly reduced (39-54%*) in TACE siRNA-treated HF rats. Compared with control HF rats, HF rats treated with TACE siRNA had reduced expression of phosphorylated (p-) NF-κB p65 (1.27±0.14 vs 0.84±0.07*), p-EGFR (0.52±0.05 vs 0.37±0.04*) and p-ERK1/2 (1.06±0.10 vs 0.62±0.09*) in the PVN. Moreover, the elevated plasma norepinephrine levels, lung/body weight, heart/body weight and left ventricular (LV) end-diastolic pressure along with decreased LV dP/dt max in HF rats-treated with control siRNA were significantly attenuated in HF rats treated with TACE siRNA. Treatments with TACE siRNA in the PVN also improved the indicators of cardiac hypertrophy and fibrosis of HF. ICV infusion of TAPI-0 had the similar effects with PVN TACE siRNA on these variables in HF. These data indicate that central interventions suppressing TACE activity ameliorate neuroinflammation, sympathetic activation and cardiac dysfunction in HF.

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