scholarly journals The Effect of Mesenchymal Stem Cells Transplantation on Cardiac Functioning and Contractility in Experimental Myocardial Infarction

Author(s):  
S. I. Estrin ◽  
T. V. Kravchenko ◽  
A. O. Kovalchuk

Introduction. Heart failure as a result of ischemic myocardial remodeling is one of the most severe diseases with poor prognosis. Drug therapy alone with surgical or percutaneous revascularization of damaged myocardium often fails to achieve optimum effect in the treatment of the mentioned syndrome. Cell cardiomyoplasty using autologous bone marrow derived mesenchymal stem cells (BM-MSCs) has already proved to be promising alternative to both these treatment methods, as it’s aimed directly at restoration of normally functioning myocard. The aim. To study the effects of different techniques of cardiomyoplasty with BM-MSCs on morphometrical and functional indices of post-infarctional left ventricular remodeling in experiment. Materials and methods. An experimental model of myocardial infarction in laboratory rats was used for the research. The survived animals were equally divided into 5 groups; the animals of 3 groups underwent BM-MSC transplantation. A certain technique of cardiomyoplasty was used in each of the 3 groups: direct injection into necrotic myocardium, intravenous injection and injection inside left ventricular cavity (which imitates intracoronalintroduction). Other 2 groups were comparison groups where the animals did not achieve BM-MSCs after infarction. There was also control group with intact animals with normal values of all the studied indices. The following invasive and noninvasive measurements of functional heart indices have been done in all research groups: left ventricular weight and its relation to body weight, end-systolic and end-diastolic left ventricular internal dimensions, fractional shortening, ejection fraction, stroke volume, heart rate, systemic arterial pressure and left ventricular inner pressure, both systolic and diastolic. The follow-up period was 1 and 3 months after the experiment. Finally, all animals were euthanized and autopsied, and the results of macroscopic examination of their hearts have been matched with aforecited functional indices in each group. Results and discussion. The analysis of all measured parameters and their comparison between groups have revealed that BM-MSC transplantation (irrespective of technique) conduces to reliably significant retention of functioning myocardium volume, reliably significant improvement of contractility parameters, particularly, reduced end-systolic and end-diastolic internal dimensions, increased ejection fraction, fractional shortening and stroke volume; it also contributes to maximal inalterability of such hemodynamic parameters as heart rate, systemic arterial pressure, left ventricular inner pressure. In addition, in all 3 groups of cell therapy the indices of contractility and pump function of the left ventricle were very close to normal rates. But the optimal results have been obtained in the group of direct intramyocardial injections. Conclusion. Cell cardiomyoplasty with BM-MSCs tends to prevent ischemic myocardial remodeling and, as a result, to improve myocardial contractility and neutralize manifestations of severe heart failure in short-term follow-up of 1 and 3 months.

Author(s):  
Ramachandran S. Vasan ◽  
Solomon K. Musani ◽  
Kunihiro Matsushita ◽  
Walter Beard ◽  
Olushola B. Obafemi ◽  
...  

Background Black individuals have a higher burden of risk factors for heart failure (HF) and subclinical left ventricular remodeling. Methods and Results We evaluated 1871 Black participants in the Atherosclerosis Risk in Communities Study cohort who attended a routine examination (1993–1996, median age 58 years) when they underwent echocardiography. We estimated the prevalences of 4 HF stages: (1) Stage 0 : no risk factors; (2) Stage A : presence of HF risk factors (hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, coronary artery disease without clinical myocardial infarction), no cardiac structural/functional abnormality; (3) Stage B : presence of prior myocardial infarction, systolic dysfunction, left ventricular hypertrophy, regional wall motion abnormality, or left ventricular enlargement; and (4) Stage C/D : prevalent HF. We assessed the incidence of clinical HF, atherosclerotic cardiovascular disease events, and all‐cause mortality on follow‐up according to HF stage. The prevalence of HF Stages 0, A, B, and C/D were 3.8%, 20.6%, 67.0%, and 8.6%, respectively, at baseline. On follow‐up (median 19.0 years), 309 participants developed overt HF, 390 incurred new‐onset cardiovascular disease events, and 651 individuals died. Incidence rates per 1000 person‐years for overt HF, cardiovascular disease events, and death, respectively, were Stage 0, 2.4, 0.8, and 7.6; Stage A, 7.4, 9.7, and 13.5; Stage B 13.6, 15.9, and 22.0. Stage B HF was associated with a 1.5‐ to 2‐fold increased adjusted risk of HF, cardiovascular disease events and death compared with Stages 0/A. Conclusions In our large community‐based sample of Black individuals, we observed a strikingly high prevalence of Stage B HF in middle age that was a marker of high cardiovascular morbidity and mortality.


Author(s):  
Mei-Zhen Wu ◽  
Yan Chen ◽  
Yu-Juan Yu ◽  
Zhe Zhen ◽  
Ying-Xian Liu ◽  
...  

Abstract Aims  Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodelling, and diastolic dysfunction in patients with type 2 diabetes (T2DM). The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodelling, and diastolic dysfunction in patients with T2DM. Further, the prognostic value of diastolic function in women and men was also evaluated. Methods and results  A total of 350 patients with T2DM (mean age 61 ± 11 years; women, 48.3%) was recruited. Detailed echocardiography was performed at baseline and after 25 months. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization, or myocardial infarction. Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 21 patients developed MACE (5 cardiovascular death, 9 hospitalization for heart failure, and 7 myocardial infarction) during a median follow-up of 56 months. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women [hazard ratio = 6.30; 95% confidence interval (CI) = 1.06–37.54; P < 0.05] but not men (hazard ratio = 2.29, 95% CI = 0.67–7.89; P = 0.19). Conclusion  LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Minushkina ◽  
V Brazhnik ◽  
N Selezneva ◽  
V Safarjan ◽  
M Alekhin ◽  
...  

Abstract   Left ventricular (LV) global function index (LVGFI) is a MRI marker of left ventricular remodeling. LVGFI has high predictive significance in young healthy individuals. The aim of the study was to assess prognostic significance in patients with acute coronary syndrome (ACS). We include into this analysis 2169 patients with ACS (1340 (61.8%) men and 829 (38.2%) women), mean age 64.08±12.601 years. All patients were observed in 2 Russian multicenter observational studies: ORACLE I (ObseRvation after Acute Coronary syndrome for deveLopment of trEatment options) (2004–2007 years) and ORACLE II (NCT04068909) (2014–2019 years). 1886 (87.0%) pts had arterial hypertension, 1539 (71.0%) – history of coronary artery disease, 647 (29.8%) – history of myocardial infarction, 444 (20.5%) - diabetes mellitus. Duration of the follow-up was 1 years after the hospital discharge. Cases of death from any cause, coronary deaths, repeated coronary events (fatal and non-fatal) were recorded. An echocardiographic study was conducted 5–7 days from the time of hospitalization. The LVGFI was defined as LV stroke volume/LV global volume × 100, where LV global volume was the sum of the LV mean cavity volume ((LV end-diastolic volume + LV end-systolic volume)/2) and myocardial volume (LV mass/density). During the follow-up, 193 deaths were recorded (8.9%), 122 deaths (5.6%) were coronary. In total, repeated coronary events were recorded in 253 (11.7%) patients. Mean LVGFI was 22.64±8.121%. Patients who died during the follow-up were older (73.03±10.936 years and 63.15±12.429 years, p=0.001), had a higher blood glucose level at the admission to the hospital (8.12±3.887 mmol/L and 7.17±3.355 mmol/L, p=0.041), serum creatinine (110.86±53.954 μmol/L and 99.25±30.273 μmol/L, p=0.007), maximum systolic blood pressure (196.3±25.17 mm Hg and 190.3±27.83 mm Hg, p=0.042). Those who died had a lower LVGFI value (19.75±6.77% and 23.01±8.243%, p<0.001). Myocardial mass index, ejection fraction and other left ventricular parameters did not significantly differ between died and alive patients. Among the patients who died, there were higher rate of women, pts with a history of myocardial infarction, heart failure, diabetes. In a multivariate analysis, diabetes mellitus OR1.67 95% CI [1.12–2.51] p=0.012, history of heart failure (1.78 [1.2.-2.59], p=0.003), a history of myocardial infarction (1.47 [1.05–2.05], p=0024), age (1.06 [1.05–1.08], p=0.001) and LVGFI <22% (1.53 [1.08–2.17], p=0.015) were independent predictors of death from any cause. The LVGFI was also independently associated with the risk of coronary death, but not with the risk of all recurring coronary events. Thus, LVGFI may be useful the marker to assess risk in patients who have experienced an ACS episode. Funding Acknowledgement Type of funding source: None


2018 ◽  
Vol 64 (9) ◽  
pp. 853-860 ◽  
Author(s):  
Roberta da Silva Teixeira ◽  
Bruna Medeiros Gonçalves de Veras ◽  
Kátia Marie Simões e Senna ◽  
Rosângela Caetano

SUMMARY INTRODUCTION Heart failure due to an acute myocardial infarction is a very frequent event, with a tendency to increase according to improvements in the treatment of acute conditions which have led to larger numbers of infarction survivors. OBJECTIVE The aim of this study is to synthesize the evidence, through a systematic review, on efficacy and safety of the device in patients with this basic condition. METHODS Studies published between January 2002 and October 2016 were analysed, having as reference databases Embase, Medline, Cochrane Library, Lilacs, Web of Science and Scopus. The selection of studies, data extraction and methodological quality assessment of studies were examined by two independent reviewers, with disagreements resolved by consensus. RESULTS Only prospective studies without control group were identified. Six studies were included, with averages of 34 participants and follow-up of 13 months. Clinical, functional, hemodynamic and quality of life outcomes were evaluated. The highest mortality rate was 8.4% with 12-month follow-up for unspecified cardiovascular reasons, and heart failure rehospitalization was 29.4% with 36-month follow-up. Statistically significant improvements were found only in some of the studies which evaluating changes in left ventricular volume indices, the distance measured by the six-minute walk test, New York Heart Association functional classification, and quality of life, in pre and post-procedure analysis. CONCLUSIONS The present review indicates that no available quality evidence can assert efficacy and safety of PARACHUTE® in the treatment of heart failure after apical or anterior wall myocardial infarction.


2017 ◽  
Vol 313 (4) ◽  
pp. H690-H699 ◽  
Author(s):  
Shayne C. Barlow ◽  
Heather Doviak ◽  
Julia Jacobs ◽  
Lisa A. Freeburg ◽  
Paige E. Perreault ◽  
...  

Ischemia-reperfusion (IR) and myocardial infarction (MI) cause adverse left ventricular (LV) remodeling and heart failure and are facilitated by an imbalance in matrix metalloproteinase (MMP) activation and the endogenous tissue inhibitors of metalloproteinase (TIMPs). We have identified that myocardial injections of recombinant TIMP-3 (rTIMP-3; human full length) can interrupt post-MI remodeling. However, whether and to what degree intracoronary delivery of rTIMP-3 post-IR is feasible and effective remained to be established. Pigs (25 kg) underwent coronary catheterization and balloon occlusion of the left anterior descending coronary artery (LAD) for 90 min whereby at the final 4 min, rTIMP-3 (30 mg, n = 9) or saline was infused in the distal LAD. LV echocardiography was performed at 3–28 days post-IR, and LV ejection fraction (EF) and LV end-diastolic volume were measured. LV EF fell and LV end-diastolic volume increased from baseline (pre-IR) values (66 ± 1% and 40 ± 1 ml, respectively, means ± standard deviation) in both groups; however, the extent of LV dilation was reduced in the rTIMP-3 group by 40% at 28 days post-IR ( P < 0.05) and the fall in LV EF was attenuated. Despite equivalent plasma troponin levels (14 ± 3 ng/ml), computed MI size at 28 days was reduced by over 45% in the rTIMP-3 group ( P < 0.05), indicating that rTIMP-3 treatment abrogated MI expansion post-IR. Plasma NH2-terminal pro-brain natriuretic peptide levels, an index of heart failure progression, were reduced by 25% in the rTIMP-3 group compared with MI saline values ( P < 0.05). Although the imbalance between MMPs and TIMPs has been recognized as a contributory factor for post-MI remodeling, therapeutic strategies targeting this imbalance have not been forthcoming. This study is the first to demonstrate that a relevant delivery approach (intracoronary) using rTIMP can alter the course of post-MI remodeling. NEW & NOTEWORTHY Myocardial ischemia and reperfusion injury remain significant causes of morbidity and mortality whereby alterations in the balance between matrix metalloproteinase and tissue inhibitor of metalloproteinase have been identified as contributory biological mechanisms. This novel translational study advances the concept of targeted delivery of recombinant proteins to modify adverse myocardial remodeling in ischemia-reperfusion injury.


2021 ◽  
Author(s):  
Bo Chen ◽  
Yinjun Yang ◽  
Jinbo Wu ◽  
Jianjiang Song ◽  
Jia Lu

Abstract Objective: Myocardial infarction (MI) is acknowledged as a major cause of heart disease related death in the world. This study aims to explore the function and mechanism of miR-17-5p-induced STAT3 in myocardial remodeling after MI.Methods: MI mice were infected by lentivirus antago-miR-17-5p vector. The expression of miR-17-5p in myocardial tissues was detected. The levels of STAT3 and specific markers of autophagy LC3-II/LC3-I, Beclin-1 and p62 were measured. Myocardial remodeling and scar size were assessed and cell apoptosis was determined. The binding of miR-17-5p and STAT3 was analyzed. The functions of miR-17-5p and STAT3 in autophagy and myocardial remodeling after MI were confirmed by functional rescue experiment after injecting STAT3 inhibitor S31-20.Results: Decreased fractional shortening, increased left ventricular systolic diameter and ventricular filling velocity were detected in MI mice. High expression of miR-17-5p was found in myocardial tissues after MI. The inhibition of miR-17-5p expression led to reduction of fibrosis of myocardial tissues, scarring, cardiomyocyte apoptosis, and expressions of LC3-II/LC3-I and Beclin-1, and increased p62 expression after MI. miR-17-5p targeted STAT3 and negatively regulated its expression. Inhibition of STAT3 level reversed the improving effect of antago-miR-17-5p on MI.Conclusion: Inhibition of miR-17-5p can inhibit myocardial autophagy through targeting STAT3, and then inhibit myocardial remodeling, thereby protecting myocardium after MI.


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.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M A E Haukilahti ◽  
T V Kentta ◽  
J Tikkanen ◽  
O Anttonen ◽  
A Aro ◽  
...  

Abstract Background Heart failure (HF) is one the leading causes of hospitalization in the Western world. Women have a lower rate of HF hospitalization and mortality compared to men. Role of 12-lead electrocardiography (ECG) as a risk marker of future HF in women is not well known. Purpose We studied the association of standard 12-lead ECG and clinical risk factors to HF hospitalization in women and in men separately from a large middle aged general population sample with a long-term follow-up. Methods Standard 12-lead ECG markers were analyzed from 10,864 subjects (48.8% women, N=5,215) of the prospective Mobile Clinic Study, and their predictive value for HF hospitalization was analyzed. Results During the follow-up (29.6±11.2 yrs.), a total of 1,743 subjects had HF hospitalization; out of these, 861 were women (49.4%). Several baseline characteristics, such as age, body mass index, blood pressure, and history of prior cardiac disease predicted the occurrence of HF both in women and men (P<0.001 for all). After adjusting for baseline variables, ECG sign of left ventricular hypertrophy (LVH) (P<0.001), and atrial fibrillation (P<0.001) were the only baseline ECG variables that predicted the future HF in women. In men, HF was predicted by fast heart rate (P=0.008), T wave inversions (P<0.001), abnormal Q waves (P=0.002), and atrial fibrillation (P<0.001). Statistically significant gender interactions in prediction of HF were observed in ECG sign of LVH (P<0.001), inferolateral T wave inversions (P=0.005), and heart rate (P=0.012). Conclusions ECG sign of LVH predicts future HF in middle-aged women independently, and T wave inversions and elevated heart rate are associated with HF hospitalization in men in. Acknowledgement/Funding Finnish Cultural Foundation, The University of Oulu Scholarship Foundation, Juho Vainio Foundation


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Moritake Iguchi ◽  
Hisashi Ogawa ◽  
Hirofumi Sugiyama ◽  
Nobutoyo Masunaga ◽  
Mitsuru Ishii ◽  
...  

Purpose: Previous reports suggested that lenient rate control was not inferior to strict rate control among patients with chronic atrial fibrillation (AF). However, the impact of heart rate (HR) on the incidence of cardiovascular events is not clearly understood. Methods: The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Kyoto, Japan. At present, follow-up data were available in 3,514 patients (median follow-up period, 842 days). 1,622 patients had chronic AF, and we obtained ECG findings in 1,561 patients. We divided these patients into three groups based on their heart rate; high-HR (HR≥110) (n=179), intermediate-HR (80≤HR<110) (n=695), and low-HR (HR<80) (n=687), and explored the cardiovascular events (composite of cardiovascular death, hospitalization for heart failure, and arrhythmic events). Results: Mean HR was 128±13 bpm, 93±8 bpm, and 67±9 bpm, respectively. High HR group was younger than other groups, but the prevalence of heart failure was the highest (44.7%, 37.0%, 32.3%; p=0.007) and left-ventricular ejection fraction was the lowest (56.5±14.6%, 60.7±11.9%, 62.7±10.5%; p<0.0001). Prescription of beta-blocker (37.4%, 28.9%, 30.0%) and diltiazem (2.8%, 2.9%, 4.2%) was comparable, but prescription of verapamil was the highest in high-HR group (19.0%, 12.4%, 8.0%; p=0.0001), and prescription of digitalis was the highest in low-HR group (14.0%, 18.2%, 23.4%; p=0.005). Mean CHADS2 score was 2.3±1.3, 2.2±1.3, and 2.2±1.4, respectively. In Kaplan-Meier analysis, the incidence of cardiovascular events was higher in high-HR groups than intermediate- and low-HR group (9.2%/year vs 5.8%/year, p=0.02), but was similar between intermediate- and low-HR group (6.2%/year vs 5.4%/year, p=0.3). The incidence of stroke or systemic embolism was comparable between the three groups (2.6%/year, 3.6%/year, 2.4%/year). Cox proportional hazard ratios [95%CI] of high- and intermediate-HR for cardiovascular events compared to low-HR were 1.63 [1.06-2.44] and 1.10 [0.81-1.79], respectively. Conclusions: Among chronic AF patients, the incidence of cardiovascular events was higher in the patients with high-HR, but was similar between intermediate- and low-HR groups.


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