Abstract P345: The Neuregulin Glial Growth Factor 2 (GGF2) Produces Sustained Improvement in Left Ventricular Function in Rats with Both Early and Established Heart Failure

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Anindita Ganguly ◽  
Erika Troy ◽  
Maya Srinivas ◽  
Andrea Vecchione ◽  
Patrick Sarmiere ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Cardiac Development ◽  
Left Ventricular ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Sustained Improvement ◽  
Delayed Initiation

Neuregulin-1β is essential for fetal cardiac development and adult cardiac function. Previous reports indicate that neuregulins improve left ventricular function in heart failure models, however the duration of the functional improvements with early or late initiation of neuregulin treatment has not been characterized. The present studies examine the effects of early and delayed initiation of intravenous GGF2 treatment on left ventricular (LV) function in rats with myocardial infarction (MI). Rats underwent surgically-induced MI by left anterior coronary artery ligation. Treatment with vehicle or GGF2 (2.6 mg/kg) was initiated at 2 or 16 w post-MI and continued once or twice weekly or once every two weeks for the in-life duration of the study (approximately 40 weeks). LV function was assessed echocardiographically up to once weekly for the duration of the study. Early and delayed initiation of GGF2 treatment caused sustained and significant improvement (p < 0.05) in both ejection fraction (EF) and fractional shortening (FS) in all regimens tested. The greatest improvements were seen with the once weekly dosing paradigm after early initiation (average EF (%) at 40 weeks post initiation of dosing: vehicle = 44.4 ± 6.0, n = 8 rats, vs. GGF2 = 64.7±6.1. n = 9 rats) and twice weekly dosing paradigm after delayed initiation (average EF (%) at 4 weeks post initiation of dosing: vehicle = 34.18±1.6, n = 7 rats, vs. GGF2 = 50.69±4.68, n = 7 rats). In addition, LV function improved when rats were re-challenged with GGF2 following an extended wash out period. This observation indicates potential efficacy for treatment paradigms that utilize intermittent dosing. These findings suggest that GGF2 produces sustained improvement in LV function after early or delayed initiation of treatment following MI in rats.

Abstract 425: Induced Pluripotent Stem Cell Derived Cardiomyocyte Tissue Engineered Scaffold Improves Left Ventricular Function and Electro-Mechanical Coupling in Rats with Heart Failure

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jordan J Lancaster ◽  
Elizabeth Juneman ◽  
Pablo Sanchez ◽  
Kyle Weigand ◽  
Talal Moukabary ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Hospital Readmissions ◽  
The United States ◽  
Left Ventricular ◽  
Dermal Fibroblasts ◽  
Coronary Artery Ligation ◽  
Mechanical Coupling ◽  
Induced Pluripotent

Background: Chronic Heart Failure (CHF) is the leading cause of hospital readmissions in the United States. It may result from systolic or diastolic dysfunction, which often coexists. Here we report the effects of delivering human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) via a bioengineered patch on left ventricular function in rats with CHF. Methods: Adult male Sprague-Dawley rats underwent left coronary artery ligation and were randomized to Sham, CHF, and hiPSC-CM patch. High purity human hiPSC-CMs were obtained from Cellular Dynamics International, seeded and co-cultured onto a vicryl matrix embedded with human dermal fibroblasts. Echocardiography was performed at 3 and 6 weeks post-randomization. Hemodynamic pressure measurements were performed at 6 weeks post-ligation with Millar solid state micromanometer catheters. Open chest Electrophysiologic (EP) mapping was performed at 6 weeks post ligation. Results: Patches constructed with hiPSC-CMs displayed synchronized and spontaneous contractions within 48hrs of culture which developed in robustness over time. At maximal robustness, contractions were visualized across the full thickness of the construct. Contractions were recorded at 36+5 beats BPM. Three weeks after implantation, the hiPSC-CM patch decreased LV EDP (45%), Tau (29%), E/e’ (23%) and increased, EF (14%), e’ (20%), and e’/a’ (36%) versus CHF. EP studies show electro-mechanical coupling between the patch and the native myocardium with normal activation through the patch and increases (P<0.05) voltage amplitude in CHF versus hiPSC-CM patch treated rats (1±0.5 mV vs 6±1.5mV). Conclusion: Cardiac patch implantation with human iPSC derived cardiomyocytes is an effective and feasible method of treating CHF with improvements in systolic function, diastolic function, and electro-mechanical coupling in rats with CHF.

Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice

2008 ◽  
Vol 294 (3) ◽  
pp. H1398-H1406 ◽  
Author(s):  
Fadi N. Salloum ◽  
Antonio Abbate ◽  
Anindita Das ◽  
Jon-Erik Houser ◽  
Colin A. Mudrick ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Ischemic Cardiomyopathy ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Coronary Artery Ligation ◽  
Protective Effects ◽  
Artery Ligation

We tested the hypothesis that chronic treatment with sildenafil attenuates myocardial infarction (MI)-induced heart failure. Sildenafil has potent protective effects against necrosis and apoptosis following ischemia-reperfusion in the intact heart and cardiomyocytes. ICR mice underwent MI by left anterior descending coronary artery ligation and were treated with sildenafil (0.71 mg/kg bid) or saline for 4 wk. Infarct size (IS) was measured 24 h postinfarction, and apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Left ventricular end-diastolic diameter (LVEDD) and fractional shortening (FS) were measured by echocardiography. Sildenafil reduced IS (40.0 ± 4.6%) compared with that in saline (69.6 ± 4.1%, P < 0.05). NG-nitro-l-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor (15 mg/kg bid), blocked the protective effect of sildenafil (IS, 60.2 ± 1.6%, P < 0.05 vs. sildenafil). Western blot analysis revealed a significant increase in endothelial NOS/inducible NOS proteins 24 h post-MI after treatment with sildenafil versus saline. Apoptosis decreased from 2.4 ± 0.3% with saline to 1.2 ± 0.1% with sildenafil ( P < 0.05) on day 7 and from 2.0 ± 0.2% with saline to 1.2 ± 0.1% with sildenafil on day 28 ( P < 0.05), which was associated with an early increase in the Bcl-2-to-Bax ratio. LVEDD increased from baseline value of 3.6 ± 0.1 to 5.2 ± 0.2 and to 5.5 ± 0.1 mm on days 7 and 28, respectively, with saline ( P < 0.05) but was attenuated to 4.4 ± 0.2 and 4.4 ± 0.1 mm following sildenafil treatment on days 7 and 28, respectively ( P > 0.05 vs. baseline). FS significantly improved post-MI with sildenafil. A marked decline in cardiac hypertrophy was observed with sildenafil, which paralleled a reduction in pulmonary edema. Survival rate was lower with saline (36%) compared with sildenafil (93%, P < 0.05). Sildenafil attenuates ischemic cardiomyopathy in mice by limiting necrosis and apoptosis and by preserving left ventricular function possibly through a nitric oxide-dependent pathway.

Abstract 249: Chronic Neuregulin-1β Treatment Mitigates the Progression of Post-myocardial Infarction Heart Failure in the Setting of Type 1 Diabetes Mellitus

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Manisha Gupte ◽  
Hind Lal ◽  
Firdos Ahmad ◽  
Lin Zhong ◽  
Douglas B Sawyer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 1 Diabetes ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Artery Ligation

Aim: Neuregulin-1β (NRG-1β), a growth factor critical for cardiac development as well as maintenance of heart function after injury has been shown to significantly improve heart function in preclinical rodent models. Importantly, number of studies are ongoing to test the efficacy of NRG-1β as a treatment for patients with chronic heart failure. However, the efficacy of recombinant NRG-1β in a typ1 diabetic model of heart failure due to myocardial infarction (MI) has not been investigated. The aim of the present study was to determine the efficacy of exogenous NRG-1β to improve residual cardiac function after MI in type1 diabetic rats. Methods and Results: Sprague Dawley rats were induced type 1 diabetes by a single injection of streptozotocin (STZ) (65 mg/kg). Two weeks after induction of type 1 diabetes, rats underwent left coronary artery ligation to induce MI. STZ-diabetic rats were treated with saline or NRG-1β (100 ug/kg) twice a week for 7 weeks, starting two weeks prior to experimental MI. Residual left ventricular (LV) function was significantly greater in the NRG-1β-treated STZ-diabetic MI group compared to the vehicle-treated STZ-diabetic MI group 5 weeks after MI as assessed by high-resolution echocardiography. Furthermore, NRG-1β treatment in STZ-diabetic MI rats reduced myocardial fibrosis and apoptosis as well as decreased gene expression of key oxidant-producing enzymes. Conclusion: This study demonstrates that augmentation of NRG-1β signaling in STZ-diabetic post-MI rats via therapy with exogenous recombinant NRG-1β will alleviate subsequent HF through improvements in residual LV function via protection against adverse remodeling and apoptosis.

Validation of echocardiographic methods for assessing left ventricular dysfunction in rats with myocardial infarction

2004 ◽  
Vol 287 (5) ◽  
pp. H2049-H2053 ◽  
Author(s):  
Eric E. Morgan ◽  
Michael D. Faulx ◽  
Tracy A. McElfresh ◽  
Theodore A. Kung ◽  
Michael S. Zawaneh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Index ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Artery Ligation ◽  
Peak Rate ◽  
Fractional Shortening

The rat infarct model is widely used in heart failure research, but few echocardiographic indexes of left ventricular (LV) function are validated in this model. Accordingly, the objective of this study was to validate a 13-segment LV wall motion score index (WMSI) and the myocardial performance index (MPI) in infarcted rats. Twenty-nine male Wistar rats underwent left coronary artery ligation or sham operation and were evaluated with two-dimensional and Doppler flow echocardiography 8 wk later. After echocardiography, invasive indexes were obtained using a high-fidelity catheter. WMSI and MPI were correlated with the invasive and noninvasive measurements of LV function. WMSI and MPI significantly correlated directly with end-diastolic pressure ( r = 0.72 and 0.42 for WMSI and MPI, respectively) and the time constant of isovolumic relaxation ( r = 0.68 and 0.48) and inversely with peak rate of rise of LV pressure (+dP/d t; r = −0.68 and −0.50), peak rate of decline in LV pressure ( r = −0.57 and −0.44), LV developed pressure ( r = −0.58 and −0.42), area fractional shortening ( r = −0.85 and −0.53), and cardiac index ( r = −0.74 and −0.74). Stepwise linear regression analyses revealed that LV end-diastolic pressure, +dP/d t, area fractional shortening, and cardiac index were independent determinants of WMSI ( r = 0.994) and that cardiac index and +dP/d t were independent determinants of MPI ( r = 0.781). We conclude that the 13-segment WMSI and MPI are reproducible and correlate strongly with established echocardiographic and invasive indexes of systolic and diastolic function. These findings support the use of WMSI and MPI as indexes of global LV function in the rat infarction model of heart failure.

scholarly journals ACE Inhibition Modulates Myeloid Hematopoiesis after Acute Myocardial Infarction and Reduces Cardiac and Vascular Inflammation in Ischemic Heart Failure

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 396
Author(s):  
Wolf-Stephan Rudi ◽  
Michael Molitor ◽  
Venkata Garlapati ◽  
Stefanie Finger ◽  
Johannes Wild ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Bone Marrow ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Vascular Inflammation ◽  
Ace Inhibition ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Ischemic Heart Failure

Aims: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a cornerstone of drug therapy after myocardial infarction (MI) and improve left ventricular function and survival. We aimed to elucidate the impact of early treatment with the ACE inhibitor ramipril on the hematopoietic response after MI, as well as on the chronic systemic and vascular inflammation. Methods and Results: In a mouse model of MI, induced by permanent ligation of the left anterior descending artery, immediate initiation of treatment with ramipril (10 mg/k/d via drinking water) reduced cardiac inflammation and the number of circulating inflammatory monocytes, whereas left ventricular function was not altered significantly, respectively. This effect was accompanied by enhanced retention of hematopoietic stem cells, Lin−Sca1−c-Kit+CD34+CD16/32+ granulocyte–macrophage progenitors (GMP) and Lin−Sca1−c-Kit+CD150−CD48− multipotent progenitors (MPP) in the bone marrow, with an upregulation of the niche factors Angiopoetin 1 and Kitl at 7 d post MI. Long-term ACE inhibition for 28 d limited vascular inflammation, particularly the infiltration of Ly6Chigh monocytes/macrophages, and reduced superoxide formation, resulting in improved endothelial function in mice with ischemic heart failure. Conclusion: ACE inhibition modulates the myeloid inflammatory response after MI due to the retention of myeloid precursor cells in their bone marrow reservoir. This results in a reduction in cardiac and vascular inflammation with improvement in survival after MI.

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