Effects of dynamic exercise training on the metabolic and cardiocirculatory responses to exercise in the rat model of myocardial infarction and heart failure

Introduction: Phosphodiesterase 9 (PDE9) controls natriuretic-peptide-stimulated cyclic guanosine monophosphate in cardiac myocytes and is stongly upregulated in human heart failure, suggesting its potential as a promising therapeutic target in heart failure. Here we investigated the potential effects of TT-00920, a clinical stage novel and highly selective PDE9 inhibitor, on heart failure in a rat model of myocardial infarction. Methods: Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation in male Sprague Dawley rats. After 4-week treatment of vehicle, LCZ696, TT-00920, or TT-00920/Valsartan by oral gavage, efficacy was assessed by echocardiography and cardiac histopathology. Results: TT-00920 had remarkably improved cardiac function, protected against cardiac remodeling and fibrosis in a dose-dependent manner. TT-00920/Valsartan combination showed superior beneficial efficacy when compared to TT-00920 or LCZ696 single agent.Figure 1. TT-00920 improved cardiac function and ventricular remodeling.Figure 2. TT-00920 attenuated cardiac fibrosis in peri-infarct zone. Conclusions: TT-00920 reversed LAD-induced left ventricular dysfunction and remodeling, supporting its potential as a novel therapeutic agent for heart failure. The superior efficacy of TT-00920/Valsartan combination suggests that TT-00920 and renin-angiotensin-aldosterone system inhibitors may have additive therapeutic effects in heart failure.TT-00920 is currently being evaluated in Phase 1 clinical study for safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers (NCT04364789).

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Psychological Effects on Patients with Myocardial Infarction after a Dynamic Exercise Training During Rehabilitation

Adapted Physical Activity ◽

10.1007/978-3-642-74873-8_49 ◽

1990 ◽

pp. 333-337 ◽

Cited By ~ 1

Author(s):

E. Eisenriegler ◽

R. Jokiel ◽

R. Heller ◽

M. Jetté ◽

G. Blümchen

Keyword(s):

Myocardial Infarction ◽

Exercise Training ◽

Dynamic Exercise ◽

Psychological Effects

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Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

Cellular Physiology and Biochemistry ◽

10.1159/000487871 ◽

2018 ◽

Vol 45 (5) ◽

pp. 1797-1806 ◽

Cited By ~ 22

Author(s):

Anbang Han ◽

Yingdong Lu ◽

Qi Zheng ◽

Jian Zhang ◽

YiZhou Zhao ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Cardiac Function ◽

Signaling Pathways ◽

Rat Model ◽

Cardiac Remodeling ◽

Left Ventricular ◽

Protective Effects ◽

Tnf Α ◽

Tgf Β1

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

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Exercise Training Corrects Control Of Diastolic Calcium In Hearts From Myocardial Infarction Heart Failure Rats

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000355086.27397.a8 ◽

2009 ◽

Vol 41 ◽

pp. 174

Author(s):

Ole J. Kemi ◽

Niall MacQuaide ◽

Morten A. Hoydal ◽

Per M. Haram ◽

Oyvind Ellingsen ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Exercise Training ◽

Infarction Heart

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Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats

Journal of Cellular Physiology ◽

10.1002/jcp.22771 ◽

2011 ◽

Vol 227 (1) ◽

pp. 20-26 ◽

Cited By ~ 13

Author(s):

Ole J. Kemi ◽

Niall MacQuaide ◽

Morten A. Hoydal ◽

Oyvind Ellingsen ◽

Godfrey L. Smith ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Exercise Training ◽

Calcium Waves ◽

Infarction Heart

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P2521Exercise-Based Cardiac Rehabilitation in post myocardial infarction patients with mid-range ejection fraction

European Heart Journal ◽

10.1093/eurheartj/ehz748.0850 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

I Burazor ◽

P Seferovic ◽

M Ostojic ◽

B Ivanovic ◽

M Andjic ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Exercise Training ◽

Ejection Fraction ◽

Secondary Prevention ◽

Cardiac Rehabilitation ◽

Prevention Program ◽

Rehabilitation Program ◽

Cardiac Rehabilitation Program ◽

Walking Test

Abstract Heart failure is a major cause of morbidity, mortality and re-hospitalizations and is highly prevalent in myocardial infarction survivors. Cardiac rehabilitation based on exercise training and heart failure self-care counseling have each been shown to improve clinical status and clinical outcomes. We designed our study with aim to evaluate the usefulness of exercise based in house cardiac rehabilitation/ secondary prevention program in patients with heart failure with mid-range ejection fraction (HFmrEF) after myocardial infarction. Patients and methods Out of 2753 patients who were admitted to our three weeks in- hospital secondary prevention program – exercised based cardiac rehabilitation, we analyze a total of 219 patients who were admitted early after coronary revascularization (percutaneus coronary interventions or coronary bypass surgery) with HFmrEF. The majority of patients were males (68%). Risk factors and co morbidities were noted. Patients were selected for exercise training after six minute walking test or exercise stress test (cardiopulmonary dominantly to evaluate unexpected exertional dyspnea). After 3 weeks in house cardiac rehabilitation the patients were re-tested. Results The major comorbidities in our patient population were as follows: hypertension, diabetes and dyslipidemia. Six minutes walking test was performed and the total distance walked ranged from 120 to 480 meters and the beginning of the program. Patient had 7 -days a week training program. After the 3 weeks in hospital exercise rehabilitation the improvement in the test was ∼32%. Cardiopulmonary test showed also improvement of functional capacity.We noted several rhythm disturbance complications by telemetry (VES, SVES). None had acutisation of heart failure (with peripheral edema and congestion). All patients fulfilled cardiac rehabilitation program. Conclusions Supervised multidisciplinary cardiac rehabilitation program, including an individualized exercise component is effective and can improve functional status and exercise tolerance in patient with HFmrEF after myocardial infarction.

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