scholarly journals Riociguat Reduces Infarct Size and Post-Infarct Heart Failure in Mouse Hearts: Insights from MRI/PET Imaging

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e83910 ◽  
Author(s):  
Carmen Methner ◽  
Guido Buonincontri ◽  
Chou-Hui Hu ◽  
Ana Vujic ◽  
Axel Kretschmer ◽  
...  
2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.


2004 ◽  
Vol 286 (1) ◽  
pp. H381-H387 ◽  
Author(s):  
Ling Chen ◽  
Chang Xun Chen ◽  
Xiaohong Tracey Gan ◽  
Norbert Beier ◽  
Wolfgang Scholz ◽  
...  

Sodium/hydrogen exchange (NHE) inhibitors show promise as potential therapeutic agents for the treatment of heart failure, but it is not known whether they can reverse the maladaptive remodeling that results in heart failure. We sought to determine the effect of the NHE-1-specific inhibitor EMD-87580 (EMD) on heart failure produced by myocardial infarction in the rat and to assess whether up to 4 wk of treatment delay results in beneficial effects. Male Sprague-Dawley rats were subjected to coronary artery ligation (or a sham procedure) and followed for up to 3 mo, at which time hypertrophy and hemodynamics were determined. EMD was provided in the diet, and treatment commenced immediately or 2–4 wk after ligation. EMD significantly reduced hemodynamic abnormalities, including the elevation in left ventricular end-diastolic pressure, and diminished the loss of systolic function with all treatment protocols. Left ventricular dilatation and hypertrophy, as assessed by heart weight, cell size, and atrial natriuretic peptide (ANP) expression, were similarly reversed to sham or near-sham levels. In addition, the increased plasma ANP and pro-ANP values were reversed to levels not significantly different from sham. Surprisingly, virtually all beneficial effects were identical with all treatment protocols. These effects were observed in the absence of infarct size reduction or blood pressure-lowering effects. Our results suggest that NHE-1 inhibition attenuates and reverses postinfarction remodeling and heart failure with a treatment delay of up to 4 wk after infarction. The effect is independent of infarct size or afterload reduction, indicating a direct effect on the myocardium.


2017 ◽  
Vol 102 (11) ◽  
pp. 1448-1458 ◽  
Author(s):  
Vítor Scotta Hentschke ◽  
Lucas Capalonga ◽  
Douglas Dalcin Rossato ◽  
Júlia Luíza Perini ◽  
Jadson Pereira Alves ◽  
...  

2014 ◽  
Vol 30 (10) ◽  
pp. S115
Author(s):  
J. Shavadia ◽  
Y. Zheng ◽  
N Dianati Maleki ◽  
F. Van ◽  
De Werf ◽  
...  

2008 ◽  
Vol 295 (3) ◽  
pp. H1191-H1197 ◽  
Author(s):  
Dmitry Sonin ◽  
Si-Yuan Zhou ◽  
Chunxia Cronin ◽  
Tatiana Sonina ◽  
Jeffrey Wu ◽  
...  

Evidence is accumulating to support the presence of P2X purinergic receptors in the heart. However, the biological role of this receptor remains to be defined. The objectives here were to determine the role of cardiac P2X receptors in modulating the progression of post-myocardial infarction ischemic heart failure and to investigate the underlying mechanism. The P2X4 receptor (P2X4R) is an important subunit of native cardiac P2X receptors, and the cardiac-specific transgenic overexpression of P2X4R (Tg) was developed as a model. Left anterior descending artery ligation resulted in similar infarct size between Tg and wild-type (WT) mice ( P > 0.1). However, Tg mice showed an enhanced cardiac contractile performance at 7 days, 1 mo, and 2 mo after infarction and an increased survival at 1 and 2 mo after infarction ( P < 0.01). The enhanced intact heart function was manifested by a greater global left ventricular developed pressure and rate of contraction of left ventricular pressure in vitro and by a significantly increased fractional shortening and systolic thickening in the noninfarcted region in vivo ( P < 0.05). The salutary effects on the ischemic heart failure phenotype were seen in both sexes and were not the result of any difference in infarct size in Tg versus WT hearts. An enhanced contractile function of the noninfarcted area in the Tg heart was likely an important rescuing mechanism. The cardiac P2X receptor is a novel target to treat post-myocardial infarction ischemic heart failure.


2015 ◽  
Vol 21 (10) ◽  
pp. S167-S168
Author(s):  
Keita Saku ◽  
Takahiro Arimura ◽  
Takamori Kakino ◽  
Takafumi Sakamoto ◽  
Takeshi Tohyama ◽  
...  

Heart ◽  
2013 ◽  
Vol 99 (suppl 2) ◽  
pp. A141-A141
Author(s):  
C Methner ◽  
T Krieg ◽  
A Vujic ◽  
G Buonincontri ◽  
A Carpenter ◽  
...  

2018 ◽  
Vol 2 (1) ◽  
pp. e000100
Author(s):  
Sergey Kozhukhov ◽  
Alexander Parkhomenko ◽  
Nataliia Dovganych

Introduction: Acute heart failure (AHF) is one of the most frequent complication of acute myocardial infarction (AMI). It is not only associated with a several-fold increase of in-hospital mortality but also, worsens the long-term survival in comparison to those without AHF. The AHF is observed to be more in AMI patients whose in-hospital stay is more than 3 days. The clinical implications and prognostic accuracy of the AHF term in the setting of AMI are yet unknown. Methods: We observed 1,104 consecutive cardiac care patients, who were admitted with ST-elevation AMI (STEMI). They were divided into groups according to the AHF presence {AHF(+) n=334 and AHF(-) n=764}. Among 334 AHF(+) patients: 252 patients were found to have a transient AHFt(+), whereas 82 of AHF(+) patients had persistent AHFp(+) during in-hospital period.  Patients' baseline characteristics, blood analysis, left ventricle (LV) and renal function data were assessed and analyzed on the admission day and 10th day post-admission. The follow-up was conducted on the 30th day and after 2 years. Results. STEMI patients accompanied by AHF(+) were older, presented mostly with anterior AMI (p<0.01), had lower LV ejection fraction (EF) (p<0.01) and a higher heart rate (p<0.05). Their rates of comorbidities and of in-hospital complications such as recurrent angina, reinfarction, LV aneurism were higher in comparision to AHF(-) patients. AHFp(+) patients had the shortest time from symptoms onset before thrombolysis in comparision to AHFt(+) and AHF(-) groups. Partial recovery of cardiac function according to Left ventricular ejection fraction (LVEF) and end-systolic volume index, occurred mainly in AHF(-) and AHFt(+) patients on the 10th day post-admission, but not in AHFp(+). STEMI patients with AHFp(+) demonstrated a larger infarct size, higher C-reactive protein and VGEF level, fasting glucose and heart rate on admission, higher erythrocyte sedimentation rate, absence of heart rate normalization on the 10th day post-admission. All of these markers were the signs of severe myocardial damage and inflammation, which can reflect worse recovery in AHF patients despite optimal management. Patients with AHF(+) had renal dysfunction on admission while its creatinine clearance (CrCl) decreased during the in-hospital period which is the reflection of a poor prognosis. Сardiovascular mortality and non-fatal MI were significantly higher in the AHFp(+) group as compared to the AHFt(+) and the AHF(–) groups during the 30 days and 2 years of follow-up. Conclusion: The AHF is a frequent STEMI complication. AHF lasting >3 days had worse short- and long-term prognosis. Therefore, an aggressive strategy should be recommended particularly in patients who have clinical signs and symptoms of persistent AHF. Keywords: myocardial infarction, acute heart failure, infarct size, survival.


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