YiQiFuMai Powder Injection attenuates coronary artery ligation-induced myocardial remodeling and heart failure through modulating MAPKs signaling pathway

2017 ◽  
Vol 202 ◽  
pp. 67-77 ◽  
Author(s):  
Li-zhi Pang ◽  
Ai-chun Ju ◽  
Xian-jie Zheng ◽  
Fang Li ◽  
Yun-fei Song ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Signaling Pathway ◽  
Powder Injection ◽  
Coronary Artery Ligation ◽  
Myocardial Remodeling ◽  
Artery Ligation

scholarly journals Inhibition of N-type calcium channels in cardiac sympathetic neurons attenuates ventricular arrhythmogenesis in heart failure

2020 ◽  
Author(s):  
Dongze Zhang ◽  
Huiyin Tu ◽  
Chaojun Wang ◽  
Liang Cao ◽  
Wenfeng Hu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Ventricular Arrhythmias ◽  
Sympathetic Neurons ◽  
Coronary Artery Ligation ◽  
Channel Blockers ◽  
Artery Ligation ◽  
Cell Excitability ◽  
Ventricular Arrhythmogenesis

Abstract Aims Cardiac sympathetic overactivation is an important trigger of ventricular arrhythmias in patients with chronic heart failure (CHF). Our previous study demonstrated that N-type calcium (Cav2.2) currents in cardiac sympathetic post-ganglionic (CSP) neurons were increased in CHF. This study investigated the contribution of Cav2.2 channels in cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Methods and results Rat CHF was induced by surgical ligation of the left coronary artery. Lentiviral Cav2.2-α shRNA or scrambled shRNA was transfected in vivo into stellate ganglia (SG) in CHF rats. Final experiments were performed at 14 weeks after coronary artery ligation. Real-time polymerase chain reaction and western blot data showed that in vivo transfection of Cav2.2-α shRNA reduced the expression of Cav2.2-α mRNA and protein in the SG in CHF rats. Cav2.2-α shRNA also reduced Cav2.2 currents and cell excitability of CSP neurons and attenuated cardiac sympathetic nerve activities (CSNA) in CHF rats. The power spectral analysis of heart rate variability (HRV) further revealed that transfection of Cav2.2-α shRNA in the SG normalized CHF-caused cardiac sympathetic overactivation in conscious rats. Twenty-four-hour continuous telemetry electrocardiogram recording revealed that this Cav2.2-α shRNA not only decreased incidence and duration of ventricular tachycardia/ventricular fibrillation but also improved CHF-induced heterogeneity of ventricular electrical activity in conscious CHF rats. Cav2.2-α shRNA also decreased susceptibility to ventricular arrhythmias in anaesthetized CHF rats. However, Cav2.2-α shRNA failed to improve CHF-induced cardiac contractile dysfunction. Scrambled shRNA did not affect Cav2.2 currents and cell excitability of CSP neurons, CSNA, HRV, and ventricular arrhythmogenesis in CHF rats. Conclusions Overactivation of Cav2.2 channels in CSP neurons contributes to cardiac sympathetic hyperactivation and ventricular arrhythmogenesis in CHF. This suggests that discovering purely selective and potent small-molecule Cav2.2 channel blockers could be a potential therapeutic strategy to decrease fatal ventricular arrhythmias in CHF.

scholarly journals Mitigation of the progression of heart failure with sildenafil involves inhibition of RhoA/Rho-kinase pathway

2011 ◽  
Vol 300 (6) ◽  
pp. H2272-H2279 ◽  
Author(s):  
Vinh Q. Chau ◽  
Fadi N. Salloum ◽  
Nicholas N. Hoke ◽  
Antonio Abbate ◽  
Rakesh C. Kukreja
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Rho Kinase ◽  
Inhibitory Effect ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Saline Treatment ◽  
Kinase Pathway ◽  
Fractional Shortening

Chronic inhibition of phosphodiesterase-5 with sildenafil immediately after permanent occlusion of the left anterior descending coronary artery was shown to limit ischemic heart failure (HF) in mice. To mimic a more clinical scenario, we postulated that treatment with sildenafil beginning at 3 days post-myocardial infarction (MI) would also reduce HF progression through the inhibition of the RhoA/Rho-kinase pathway. Adult male ICR mice with fractional shortening < 25% at day 3 following permanent left anterior descending coronary artery ligation were continuously treated with either saline (volume matched, ip, 2 times/day) or sildenafil (21 mg/kg, ip, 2 times/day) for 25 days. Echocardiography showed fractional shortening preservation and less left ventricular end-diastolic dilatation with sildenafil treatment compared with saline treatment at 7 and 28 days post-MI ( P < 0.05). Both fibrosis and apoptosis, determined by Masson's trichrome and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), respectively, were attenuated in the sildenafil-treated mice ( P < 0.05 vs. saline). Western blot analysis showed enchanced Bcl-2-to-Bax ratio with sildenafil treatment ( P < 0.05 vs. saline). Activity assay showed sildenafil-mediated PKG activation 1 day after treatment ( P < 0.05 vs. sham and saline). PKG activation was associated with sildenafil-mediated inhibition of Rho kinase ( P < 0.05) compared with saline treatment, whereas PKG inhibition with KT-5823 abolished this inhibitory effect of sildenafil. In conclusion, for the first time, our findings show that chronic sildenafil treatment, initiated at 3 days post-MI, attenuates left ventricular dysfunction independent of its infarct-sparing effect, and this cardioprotection involves the inhibition of the RhoA/Rho-kinase pathway. Sildenafil may be a promising therapeutic tool for advanced HF in patients.

scholarly journals ERK1/2 MAPK signaling in hypothalamic paraventricular nucleus contributes to sympathetic excitation in rats with heart failure after myocardial infarction

2016 ◽  
Vol 310 (6) ◽  
pp. H732-H739 ◽  
Author(s):  
Yang Yu ◽  
Shun-Guang Wei ◽  
Zhi-Hua Zhang ◽  
Robert M. Weiss ◽  
Robert B. Felder
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Paraventricular Nucleus ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Mapk Signaling ◽  
Coronary Artery Ligation ◽  
Nerve Activity ◽  
Artery Ligation

Brain MAPK signaling pathways are activated in heart failure (HF) induced by myocardial infarction and contribute to augmented sympathetic nerve activity. We tested whether decreasing ERK1/2 (also known as p44/42 MAPK) signaling in the hypothalamic paraventricular nucleus (PVN), a forebrain source of presympathetic neurons, would reduce the upregulation of sympathoexcitatory mediators in the PVN and augmented sympathetic nerve activity in rats with HF. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce HF, with left ventricular dysfunction confirmed by echocardiography. One week after coronary artery ligation or sham operation, small interfering (si)RNAs targeting ERK1/2 or a nontargeting control siRNA was microinjected bilaterally into the PVN. Experiments were conducted 5–7 days later. Confocal images revealed reduced phosphorylated ERK1/2 immunofluorescence in the PVN of HF rats treated with ERK1/2 siRNAs compared with HF rats treated with control siRNA. Western blot analysis confirmed significant reductions in both total and phosphorylated ERK1/2 in the PVN of HF rats treated with ERK1/2 siRNAs along with reduced expression of renin-angiotensin system components and inflammatory mediators. HF rats treated with ERK1/2 siRNAs also had reduced PVN neuronal excitation (fewer Fos-related antigen-like-immunoreactive neurons), lower plasma norepinephrine levels, and improved peripheral manifestations of HF compared with HF rats treated with control siRNAs. These results demonstrate that ERK1/2 signaling in the PVN plays a pivotal role in mediating sympathetic drive in HF induced by myocardial infarction and may be a novel target for therapeutic intervention.

Heart failure and greater infarct expansion in middle-aged mice: a relevant model for postinfarction failure

2002 ◽  
Vol 282 (2) ◽  
pp. H615-H621 ◽  
Author(s):  
Kenneth E. Gould ◽  
George E. Taffet ◽  
Lloyd H. Michael ◽  
Robert M. Christie ◽  
Debra L. Konkol ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Systolic Function ◽  
Coronary Artery Ligation ◽  
Myocardial Repair ◽  
Artery Ligation ◽  
Aged Mice ◽  
Septal Hypertrophy ◽  
Infarct Expansion ◽  
Young Mice

Young mice tolerate myocardial loss after coronary artery ligation (CAL) without congestive heart failure (CHF) signs or mortality. We predicted a CHF phenotype after CAL in aged mice. Left coronary artery ligation produced permanent myocardial infarcts (MI). Mortality was higher in male 14-mo-old C57BL/6N mice (Older mice) than in 2-mo-old mice (Young mice) (16 of 25 Older mice died vs. 0 of 10 Young mice, P < 0.02). After 8 wk, rales, weight loss, and lethargy preceded deaths. Captopril (50 mg · kg−1 · day−1) increased Older mouse survival (6 of 22 died, P < 0.02). Captopril improved systolic function (peak aortic blood velocity) from 76 ± 6% of baseline in untreated Older mice to 93 ± 8% ( P < 0.036). At 24 h, MI comprised 28 ± 4% of the left ventricle in Young mice, surprisingly larger than that in Older mice (18 ± 2%, P < 0.011). Endocardial area underlying the infarct scar was significantly larger in Older mice than in Young mice. Captopril did not reduce expansion but markedly reduced septal hypertrophy. Aging reduces compensatory ability in mice despite smaller acute infarcts. Less effective myocardial repair, greater infarct expansion, and septal hypertrophy are seen with aging. Aging is a more relevant murine model of post-MI heart failure in patients.

Na+/H+ exchange inhibition reduces hypertrophy and heart failure after myocardial infarction in rats

2001 ◽  
Vol 280 (2) ◽  
pp. H738-H745 ◽  
Author(s):  
Keiji Kusumoto ◽  
James V. Haist ◽  
Morris Karmazyn
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Hydrogen Exchange ◽  
Diastolic Pressure ◽  
Control Diet ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Large Infarct

We investigated the effect of sodium/hydrogen exchange inhibition (NHE-1) on hypertrophy and heart failure after coronary artery ligation (CAL) in the rat. Animals were subjected to occlusion (or sham) of the left main coronary artery and immediately administered a control diet or one consisting of the NHE-1 inhibitor cariporide for 13–15 wk. Hearts were separated by small [≤30% of left ventricle (LV)] and large (>30% of LV) infarcts. CAL depressed change in left ventricular increase in pressure over time (LV +dP/d t) in small and large infarct groups by 18.8% ( P < 0.05) and 34% ( P < 0.01), respectively, whereas comparative values for the cariporide groups were 8.7% (not significant) and 23.1% ( P < 0.01), respectively. LV end-diastolic pressure was increased by 1,225% in the control large infarct group but was significantly reduced to 447% with cariporide. Cariporide also significantly reduced the degree of LV dilation in animals with large infarcts. Hypertrophy, defined by tissue weights and cell size, was reduced by cariporide, and shortening of surviving myocytes was preserved. Infarct sizes were unaffected by cariporide, and the drug had no influence on either blood pressure or the depressed inotropic response of infarcted hearts to dobutamine. These results suggest an important role for NHE-1 in the progression of heart failure after myocardial infarction.

Normal contractions triggered by I Ca,L in ventricular myocytes from rats with postinfarction CHF

2002 ◽  
Vol 283 (3) ◽  
pp. H1225-H1236 ◽  
Author(s):  
Ivar Sjaastad ◽  
Janny Bøkenes ◽  
Fredrik Swift ◽  
J. Andrew Wasserstrom ◽  
Ole M. Sejersted
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Coronary Artery ◽  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Cardiac Contractility ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Fractional Shortening

Attenuated L-type Ca2+ current ( I Ca,L), or current-contraction gain have been proposed to explain impaired cardiac contractility in congestive heart failure (CHF). Six weeks after coronary artery ligation, which induced CHF, left ventricular myocytes from isoflurane-anesthetized rats were current or voltage clamped from −70 mV. In both cases, contraction and contractility were attenuated in CHF cells compared with cells from sham-operated rats when cells were only minimally dialyzed using high-resistance microelectrodes. With patch pipettes, cell dialysis caused attenuation of contractions in sham cells, but not CHF cells. Stepping from −50 mV, the following variables were not different between sham and CHF, respectively: peak I Ca,L (4.5 ± 0.3 vs. 3.8 ± 0.3 pApF−1 at 23°C and 9.4 ± 0.5 vs. 8.4 ± 0.5 pApF−1 at 37°C), the bell-shaped voltage-contraction relationship in Cs+ solutions (fractional shortening, 15.2 ± 1.0% vs. 14.3 ± 0.7%, respectively, at 23°C and 7.5 ± 0.4% vs. 6.7 ± 0.5% at 37°C) and the sigmoidal voltage-contraction relationship in K+ solutions. Caffeine-induced Ca2+ release and sarcoplasmic reticulum Ca2+-ATPase-to-phospholamban ratio were not different. Thus CHF contractions triggered by I Ca,L were normal, and the contractile deficit was only seen in undialyzed cardiomyocytes stimulated from −70 mV.

Sign in / Sign up

Export Citation Format

Share Document