Abstract 16368: Establishment of Administration Protocol of Immunosuppressive Drug for Ips Cell Derived Cardiomyocytes Patch Transplantation in Rat Myocardial Infarction Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Emiko Ito ◽  
Shigeru Miyagawa ◽  
Ai Kawamura ◽  
Maki Takeda ◽  
Takuji Kawamura ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Immunosuppressive Agent ◽  
Immunosuppressive Drug ◽  
Tumor Formation ◽  
Sham Operation ◽  
Ips Cell ◽  
Treatment Groups ◽  
Group 2 ◽  
Immunosuppressant Treatment

Background: Although Cardiomyogenesis therapy using iPS cells for heart failure should overcome immune rejection because of allogenic cell source, appropriate protocol of immunosuppressant to promise efficacy and safety has not been fully elucidated. In this study, we investigated the duration of immunosuppressant administration that could promise the efficacy of human iPS cell derived cardiomyocytes (hiPSCs-CM) patch transplantation as well as safety. Methods: The hiPSCs-CM patch were transplanted to myocardial infarction model rats with normal immune function in immunosuppressant treatment groups. Control were underwent sham operation and treated with no immunosuppressant (Group1). Immunosuppressant treatment groups were divided into three groups as follows: treated with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisolone (PSL) for 1month and 1 month tapering period (Group2); treated with TAC, MMF, and PSL for 2month and 1 month tapering period (Group3); and treated with TAC, MMF, and PSL for 3month and 1 month tapering period (Group4). After 6 months, cardiac function and histology were analyzed. Results: hiPSC-CM patch transplantation showed significant improvement cardiac fraction compared to the Group1 (ΔLVEF; Group2 22 ± 3 %, Group3 28 ± 5 %, Group4 23 ± 4 % versus Group1 -15 ± 8 %, P < 0.05) and did not show any differences in immunosuppressant treated groups. The hiPSCs-CM patch were detected for 2 months post-transplant and Improved Cardiac functions were maintained for at least 6 months despite disappearance of the transplanted patch. Fibrosis and cardiomyocyte size were significantly ameliorated in Group2-4 compared with Group1, however, there were significant differences in immunosuppressant treated groups. Furthermore, the Group 2, 3 and 4 showed a greater amount of structurally mature blood vessels compared with Group1, however, there were no significant in immunosuppressant treated groups. Tumor formation was not observed 6 months after transplantation in the Group 2, 3 and 4. Conclusion: 2 months administration of immunosuppressive agent may promise the safety and efficacy of hiPSCs-CM patch transplantation for rat ischemic heart failure model, proposing appropriate recipe of immunosuppressant in clinical trial.

scholarly journals The Effects of Velvet Antler of Deer on Cardiac Functions of Rats with Heart Failure following Myocardial Infarction

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Ming-Jing Shao ◽  
Shuo-Ren Wang ◽  
Ming-Jing Zhao ◽  
Xi-Ling Lv ◽  
Hao Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Therapeutic Effects ◽  
Distilled Water ◽  
Functional Parameters ◽  
Related Theory ◽  
Cardiac Functions ◽  
Velvet Antler

Velvet antler of deer (VAD) is a commonly-used kidney-Yang supplementing traditional Chinese medication. According to the heart-kidney-related theory, heart Yang originates in kidney Yang and heart failure due to heart Yang deficiency can be treated by tonifying kidney Yang. In this study, we investigated therapeutic effects of VAD on cardiac functions in rats with heart failure following myocardial infarction. Forty-eight male Wistar rats were subjected either to left coronary artery ligation (N=36) or to sham operation (N=12). One week after the surgery, rats with heart failure received daily treatment of double-distilled water, captopril or VAD by gavage for consecutively four weeks, while sham-operated animals were given double-distilled water. Ultrasonic echocardiography was adopted to examine cardiac structural and functional parameters and serum brain natriuretic peptide (BNP) concentration was measured using radioimmunoassay. We found that VAD partially reversed changes in cardiac functional parameters and serum BNP levels in rats with heart failure. These results provide further evidence for the heart-kidney-related theory and suggest that VAD might be a potentially alternative and complementary medicine for the treatment of heart failure.

scholarly journals Elevated Swelling-Activated Chloride Current Densities in Hypertrophied Ventricular Myocytes in a Rabbit Heart Failure Model

2019 ◽  
Vol 22 (2) ◽  
pp. E107-E111
Author(s):  
Hongwei Shi ◽  
Zhenming Jiang ◽  
Teng Wang ◽  
Yongting Chen ◽  
Feng Cao
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Protein Expression ◽  
Diastolic Pressure ◽  
Rabbit Model ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sham Operation ◽  
Failure Group

Background: The status of the swelling-activated chloride channel (ICl, swell) during heart failure remains unclear. This study aimed to investigate whether the ICl, swell activity is altered during heart failure and to determine how the ICl, swell influences atrial arrhythmias of the failing heart. Methods: We established a heart failure rabbit model and analyzed the hemodynamic indicators 8 weeks after myocardial infarction, which include left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVDEP). Five untreated rabbits and 5 receiving a sham operation served as the control group. Left auricular appendage tissues were obtained and CLCN3 mRNA/CLCN3 protein expression levels were examined by using reverse transcription–polymerase chain reaction and Western blot, respectively. Results: Compared to the control group, the heart failure group showed a significantly decreased LVSP (14.2 ± 0.27 versus 16.9 ± 0.86 kPa, P <.05)and elevated LVDEP (2.49 ± 0.30 versus 0.15 ± 0.03 kPa, P <.05), indicating that myocardial infarction leads to progressive heart failure of rabbits in the heart failure group. CLCN3 mRNA and CLCN3 protein expression were both significantly elevated in the heart failure group compared to the control group (P <.05). Conclusion: In sum, we propose that the dynamic nature of ICl, swell upregulation may contribute to the elevated expression of CLCN3 mRNA and CLCN3 protein, resulting in myocardial cell remodeling induced by heart failure. However, further study is needed to investigate the potential functions of ICl, swell, especially the relation between ICl, swell augmentation and arrhythmia after heart failure.

scholarly journals Biomarkers of Systemic Versus Local Inflammation During the Acute Phase of Myocardial Infarction, as Predictors of Post-infarction Heart Failure

2021 ◽  
Vol 7 (3) ◽  
pp. 70-76
Author(s):  
Botond Matyas ◽  
Stefania Polexa ◽  
Imre Benedek ◽  
Andreea Buicu ◽  
Theodora Benedek
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Systemic Inflammation ◽  
Cell Adhesion Molecules ◽  
Ventricular Dysfunction ◽  
Serum Biomarkers ◽  
Group 2 ◽  
Infarction Heart ◽  
Group 1

Abstract Background: The aim of this study was to investigate the correlation between serum biomarkers of left ventricular dysfunction and systemic inflammation in the first days after the acute episode, and to investigate their role for early identification of patients at high risk for post-infarction heart failure. Materials and methods: In total, 123 subjects admitted to the Intensive Cardiovascular Care Unit of the Cardiology Clinic of the Târgu Mureș County Clinical Emergency Hospital, Romania, with acute myocardial infarction were retrospectively analyzed in this study. Based on the level of NT-proBNP, the study population was divided into 2 groups: Group 1 (n = 92), with NT-proBNP <3,000 pg/mL, and Group 2 (n = 31), with NT-proBNP >3,000 pg/mL. Results: Biomarkers reflecting systemic inflammation presented significantly higher values in patients with elevated NT-proBNP (hs-CRP – 12.3 ± 8.9 mg/L vs. 3.6 ± 6.7 mg/L, p <0.0001, and interleukin 6 – 27.6 ± 30.7 pg/mL vs. 8.6 ± 6.2 pg/mL, p <0.0001). However, cell adhesion molecules VCAM and ICAM were not significantly different between the groups. Patients in Group 2 presented significantly higher rates of major cardiovascular events and rehospitalizations in the first year after the acute coronary event, with 13.33% event rate for patients in Group 2 compared to 8.7% in Group 1 (p <0.05). Conclusions: Serum biomarkers of ventricular dysfunction are strongly associated with systemic inflammation and ventricular impairment in the immediate phase after an acute myocardial infarction. Systemic inflammation has a higher impact on the clinical outcomes and progression to heart failure than the local coronary inflammation expressed by cell adhesion molecules.

The clinical course of atrial fibrillation in patients with coronary heart disease

2016 ◽  
Vol 94 (8) ◽  
pp. 591-595 ◽  
Author(s):  
V. I. Podzolkov ◽  
Aida I. Tarzimanova ◽  
R. G. Gataulin
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Chronic Heart Failure ◽  
Clinical Course ◽  
History Of ◽  
Group 2 ◽  
Group 1

The modern medical literature practically does not contain clinical publications reporting studies of factors responsible for progression of atrial fibrillation (AF) in patients with coronary heart disease (CHD). It accounts for the importance of investigations into evolution of the clinical course of AF in such patients.Aim. To elucidate evolution of the clinical course of AF in patients with CHD in a long-term prospective study.Materials and methods. The study included. 112 patient aged 57-74 (mean 67.44±3.3) years with CHD and paroxysmal form of AF carried outfrom 2011 to 2015. Evolution of the clinical course of AF was evaluated based on the number of arrhythmic attacks during the last 3 months. The appearance ofprolonged persistent AF episodes or permanent AF was regarded as progression of arrhythmia.Results. During the 4 year study, 64 (57,2%) patients (group 1) did not experiencea rise in the frequency and duration of AF attacks. Progression of arrhythmia was documented in 48 (42,8%) of the 112 (100%) patients (group 2). These patients more frequently had the history of myocardial infarction and chronic heart failure than patients of group 1. The latter had the mean values of left ventricular (LV) ejection fraction 61,23±6,24%, i.e. significantly higher than 48,47±8,4% in group 2.47 and 28 % of the patients in group 2and 1 respectively suffered mitral regurgitation (p<0,05). Patients of group 2 had significantly more akineticzones. Intake of nitroglycerin in group 1 resulted in positive dynamics of local LV contractility that did not change in patients of group 2. Conclusion. 42,8% of the patients with CHD and paroxysmal form of AF experienced progression of arrhythmia into a persistent or permanent form. Predictors of AF progression in patients with CHD are the history of myocardial infarction, chronic heart failure, mitral regurgitation, and irreversible changes in local myocardial LV contraction.

G-CSF Stimulation and Coronary Reinfusion of Mobilized Circulating Mononuclear Proangiogenic Cells in Patients with Chronic Ischemic Heart Disease: Five-Year Results of the TOPCARE-G-CSF Trial

2012 ◽  
Vol 21 (11) ◽  
pp. 2325-2337 ◽  
Author(s):  
Joerg Honold ◽  
Ulrich Fischer-Rasokat ◽  
Ralf Lehmann ◽  
David M. Leistner ◽  
Florian H. Seeger ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Heart Disease ◽  
Nyha Class ◽  
Ischemic Heart ◽  
Lv Function ◽  
Chronic Ischemic Heart Disease ◽  
Treatment Groups ◽  
Cardiopulmonary Exercise

Prognosis of patients with heart failure remains poor despite improved conventional and interventional treatment regimens. The improvement of neovascularization and repair processes by administration of bone marrow-derived cells modestly improved the recovery after acute myocardial infarction. However, circulating patient-derived cells are reduced in number and function particularly in chronic heart failure. Therefore, we tested the hypothesis whether the mobilization of circulating mononuclear proangiogenic cells (CPCs) by G-CSF may overcome some of these limitations. In the present pilot study, 32 patients with at least 3-month-old myocardial infarction were randomized to G-CSF alone (G-CSF group) or intracoronary infusion of G-CSF-mobilized and cultured CPCs into the infarct-related artery (G-CSF/CPC group). Primary endpoint of the study was safety. Efficacy parameters included serial assessment of LV function, NT-proBNP levels, and cardiopulmonary exercise testing. G-CSF effectively mobilized circulating CD34+CD45+ cells after 5 days in all patients (408 ± 64%) without serious adverse events. At 3 months, NYHA class and global LV function did not show significant improvements in both treatment groups (G-CSF: ΔLVEF 1.6 ± 2.4%; p = 0.10; G-CSF/CPC: ΔLVEF 1.4 ± 4.1%; p = 0.16). In contrast, target area contractility improved significantly in the G-CSF/CPC group. During 5-year follow-up, one patient died after rehospitalization for worsening heart failure. Eleven patients underwent further revascularization procedures. NT-proBNP levels, cardiopulmonary exercise capacity, and NYHA class remained stable in both treatment groups. The results from our pilot trial indicate that administration of G-CSF alone or G-CSF-mobilized and cultured CPCs can be performed safely in patients with chronic ischemic heart disease. However, only minor effects on LV function, NT-proBNP levels, and NYHA classification were observed during follow-up, suggesting that the enhancement of CPCs by G-CSF alone does not substantially improve intracoronary cell therapy effects in patients with chronic ischemic heart failure.

scholarly journals Yiqi Huoxue Recipe Improves Heart Function through Inhibiting Apoptosis Related to Endoplasmic Reticulum Stress in Myocardial Infarction Model of Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Li-Xia Lou ◽  
Ai-Ming Wu ◽  
Dong-Mei Zhang ◽  
Sheng-Xian Wu ◽  
Yong-Hong Gao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Heart Function ◽  
Tunel Staining ◽  
Sham Operation ◽  
Er Stress Response ◽  
Stress Response Pathway

Objective. To explore the mechanism of cardioprotective effects of Chinese medicine, Yiqi Huoxue recipe, in rats with myocardial infarction- (MI-) induced heart failure.Methods. Male Sprague-Dawley rats underwent left anterior descending artery (LAD) ligation or sham operation. The surviving MI rats were divided randomly into three groups: MI (5 mL/kg/d NS by gavage), MI + Metoprolol Tartrate (MT) (12 mg/kg/d MT by gavage), and MI + Yiqi Huoxue (5 mL/kg recipe by gavage). And the sham operation rats were given 5 mL/kg/d normal saline. Treatments were given on the day following surgery for 4 weeks. Then rats were detected for heart structure and function by transthoracic echocardiography. Apoptosis in heart tissues was detected by TUNEL staining. To determine whether the endoplasmic reticulum (ER) stress response pathway is included in the cardioprotective function of the recipe, ER stress related proteins such as GRP78 and caspase-12 were examined.Results. Yiqi Huoxue recipe attenuated heart function injury, reversed histopathological damage, alleviated myocardial apoptosis and inhibited ER stress in MI rats.Conclusion. All the results suggest that Yiqi Huoxue recipe improves the injured heart function maybe through inhibition of ER stress response pathway, which is a promising target in therapy for heart failure.

scholarly journals LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Po-Cheng Chang ◽  
Shien-Fong Lin ◽  
Yen Chu ◽  
Hung-Ta Wo ◽  
Hui-Ling Lee ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Western Blot ◽  
Sham Group ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Vehicle Group ◽  
Sham Operation ◽  
Channel Proteins ◽  
Enalapril Therapy

Background. LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear. Methods. We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week after MI to confirm the development of HF with left ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. The sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins. Results. The HF-vehicle group did not show significant changes in LVEF. Both enalapril and LCZ696 therapy significantly improved LVEF. The HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy significantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed significant downregulation of NaV1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2. Conclusion. As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K+ channel proteins.

P6437Growth differentiation factor-15 and stromal cell-derived factor-1 as long-term prognosis biomarkers in acute coronary syndrome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O M Peiro Ibanez ◽  
N Farre ◽  
J Ordonez-Llanos ◽  
A Garcia ◽  
G Bonet ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Combined Use ◽  
Group 3 ◽  
Stromal Cell Derived Factor ◽  
Group 2 ◽  
Long Term Prognosis ◽  
Group 1

Abstract Introduction After an acute coronary syn bdrome (ACS) patients are at high risk of cardiovascular morbidity and mortality. In this scenario, Growth differentiation factor-15 (GDF-15) and Stromal cell derived factor-1 (SDF-1) has been reported as potential biomarkers in ACS. However, there is limited data about their combined use in long-term prognosis. Purpose To study the long-term prognostic value of GDF-15 and SDF-1 in ACS. Methods We included patients with ACS who underwent coronary angiography. During angiography an arterial blood sample was collected. Plasma SDF-1 and GDF-15 were measured and clinical data and long-term events were obtained. The cut-off point of SDF-1 and GDF-15 was identified individually by receiver operating characteristic curves. Patients were classified into 3 groups: 1) both biomarkers below cut-off points; 2) only one biomarker above cut-off points; 3) both biomarkers above cut-off points. Results A total of 238 patients were included. The median (IQR) age was 64 (55–74) year and 27.3% were female. Of all patients, 60.9% were admitted with non-ST-elevation myocardial infarction, 22.7% with ST-elevation myocardial infarction and 16.4% with unstable angina. The cut-off point of SDF-1 was 3283.5pg/mL and GDF-15 was 1849ng/L. A total of 127 patients were in group 1, 64 in group 2 and 47 in group 3. Group 3 patients were associated with older age, hypertension, dyslipidemia, diabetes mellitus and history of myocardial infarction (MI), stroke, chronic kidney disease and peripheral artery disease. Besides, they were more likely to have left ventricular dysfunction (ejection fraction <40%) and significant three vessels stenosis. During 6.5 years of follow-up 8 patients died (6.3%) in group 1, 7 patients died (10.9%) in group 2 and 25 patients died (53.2%) in group 3 (Figure 1). Multivariate Cox analysis showed that high levels of SDF-1 and GDF-15 (group 3) were an independent predictor of all-cause death (HR 5.8; 95% CI 2.4 - 14.1; p<0.001) and the composite of major adverse cardiovascular events (MACE) which were identified as all-cause death, nonfatal MI and heart failure (HR 3.9; 95% CI 2.1 - 7.3; p<0.001). During follow-up 1 patient had heart failure in group 1 (0.8%), 3 patients (4.7%) in group 2 and 9 patients (19.1%) in group 3. Despite the low number of events of heart failure, the multivariate competing risks regression showed association between group 3 and heart failure during follow-up (HR 28.0; 95% CI 3.5 - 225.2; p=0.002). Higher levels of SDF-1 and GDF-15 (group 3) were not associated with new MI in multivariate competing risks regression. Regarding group 2, all multivariate analyses were non-significant. Cumulative survival and incidence curves Conclusions Higher values of combined GDF-15 and SDF-1 are an excellent predictor of all-cause death, MACE and heart failure in long-term follow-up of patients with ACS. The combined use of SDF-1 and GDF-15 may be useful in long-term ACS prognosis.

The effect of empagliflozin on the development of chronic heart failure after myocardial infarction according to a 12-month prospective study

2019 ◽  
Vol 22 (4) ◽  
pp. 348-357
Author(s):  
Alexey A. Nekrasov ◽  
Elena S. Timoschenko ◽  
Leonid G. Strongin ◽  
Tatyana A. Nekrasova ◽  
Anastasiya A. Baranova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Glycemic Control ◽  
Ejection Fraction ◽  
Group 2 ◽  
Minute Walk ◽  
Group 1

BACKGROUND: Although the positive cardiovascular effect of empagliflozin has been established, its influence on the formation of heart failure (HF) in patients with type 2 diabetes mellitus (T2D) after myocardial infarction (MI) remains unknown. AIM: To study the effect of empagliflozin on the formation of chronic HF after MI in patients having diabetes mellitus of type 2 (DM 2), according to 12-month follow-up data. MATERIALS AND METHODS: 47 patients with MI and DM 2 were included; 21 received standard therapy for MI and diabetes (group 1); 26 patients, in addition, received empagliflozin (group 2). The patients were investigated in 3 and 12 months, to assess the dynamics of glycemic control, 6-minute walk test, echocardiography. RESULTS: During postinfarction period, the 6-minute walk distance was increasing in group 1 in a lesser degree (p = 0.18) than in group 2 (49.5%, p = 0.0004). The ejection fraction got better particularly in group 2 (p = 0.002). At baseline, the proportions of patients having HF with reduced and mid-range ejection fraction were 85.7% and 82.4% in groups 1 and 2 (p = 0.56) but in 12 months decreased to 71.4% and 29.4% (p = 0.012). In empagliflozin group diastolic function was improved in a third of the patients (p = 0.041). The pulmonary artery systolic pressure was increasing in group 1 (by 10,4%, p = 0.041) but decreasing in group 2 (by 24,0%, p = 0.019). Glycemic control was better in group 2 than in group 1. CONCLUSION: According to 12-month follow-up data, empagliflozin has a positive effect on HF formation and symptoms in patients having MI and DM 2. This effect may be based on the ability of empagliflozin to improve the state of the heart including the delay of postinfarction remodeling, the improvement of pulmonary artery hemodynamics, systolic and diastolic function, the reduction of risk of chronic HF with reduced and mid-range ejection fraction.

Role of nitric oxide in mediating cardiovascular alterations accompanying heart failure in rats

2004 ◽  
Vol 82 (6) ◽  
pp. 372-379 ◽  
Author(s):  
Valdeci da Cunha ◽  
Ivanita Stefanon ◽  
José Geraldo Mill
Keyword(s):  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Left Ventricular ◽  
Maximal Response ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Media Thickness ◽  
Aortic Media

The present study was designed to evaluate the role of endothelial NO in the hemodynamics and vascular changes that occur in heart failure following myocardial infarction in rats. Left ventricular systolic pressure (LVSP), mean blood pressure (MBP), aortic morphology (media thickness) and reactivity were evaluated in rats with coronary artery ligation (heart failure, HF) or sham operation (SO) untreated or treated for four weeks with either a low dose of NG-nitro-L-arginine methyl ester (L-NAME, 6 mg·kg-1·day-1) or L-arginine (1.5 g·kg-1·day-1). In rats with HF LVSP (HF = 111 ± 8 mmHg; SO = 143 ± 6 mmHg, p < 0.05), MBP (HF = 98 ± 8 mmHg; SO = 127 ± 6 mmHg, p < 0.05) and aortic media thickness (HF = 68 ± 6 µm; SO = 75 ± 2 µm, p < 0.05) were significantly reduced. The contractile response to phenylephrine and the endothelium-independent relaxation to sodium nitroprusside were similar in HF and SO aortas, but the sensitivity (pD2) to acetylcholine (HF = 7.5 ± 0.06; SO = 7.1 ± 0.08, p < 0.05) was significantly increased in HF aortas, indicating an enhanced basal NO release. Treatment with L-NAME (LN) reversed the effects of HF on LVSP (HF-LN = 143 ± 9 mmHg, p < 0.05 vs. HF), MBP (HF-LN = 128 ± 8 mmHg, p < 0.05 vs. HF), sensitivity to acetylcholine (HF-LN = 6.9 ± 0.10, p < 0.05 vs. HF) and aortic media thickness (HF-LN = 79 ± 2 µm, p < 0.05 vs. HF), without changing these parameters in SO rats. L-NAME also selectively increased the maximal response to phenylephrine in HF aortas (HF-LN = 2.4 ± 0.20 g; HF = 1.6 ± 0.17 g, p < 0.05). L-arginine (LA) did not change the effects of HF on LSVP, MBP or aortic media thickness, but it reduced the sensitivity to phenylephrine in aortas from SO rats (SO-LA = 6.5 ± 0.12; SO = 7.0 ± 0.09, p < 0.05). Taken together, these results suggest an important role for endothelial NO in mediating the reduced vascular growth, myocardial dysfunction and hypotension in rats with HF.Key words: nitric oxide, myocardial infarction, heart failure, vascular reactivity.

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