scholarly journals Is Skeletal Myoblast Transplantation Clinically Relevant in the Era of Angiotensin-Converting Enzyme Inhibitors?

Circulation ◽  
2001 ◽  
Vol 104 (suppl_1) ◽  
Author(s):  
Bruno Pouzet ◽  
Saïd Ghostine ◽  
Jean-Thomas Vilquin ◽  
Isabelle Garcin ◽  
Marcio Scorsin ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Cell Transplantation ◽  
Ace Inhibitors ◽  
Culture Medium ◽  
Ace Inhibitor ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Coronary Artery Ligation ◽  
Ventricular Ejection Fraction

Background There is compelling experimental evidence that autologous skeletal muscle (SM) cell transplantation improves postinfarction cardiac function. This study assessed whether this benefit is still manifested in the clinically relevant setting of a treatment by ACE inhibitors. Methods and Results A myocardial infarction was created in 99 rats by coronary artery ligation. They were divided into 4 groups. Two groups did not receive any drug and were intramyocardially injected 7 days after the infarct with either culture medium alone (control rats, n=16) or autologous SM cells (2.3×10 6 myoblasts) previously expanded ex vivo for 7 days (myoblasts, n=24). Two other groups received the ACE inhibitor perindoprilat (1 mg · kg −1 · d −1 ), started the day of the infarct and continued uninterruptedly thereafter, and underwent time-matched procedures, that is, they were intramyocardially injected at 7 days after infarction with either culture medium alone (ACE inhibitors, n=22) or autologous SM cells (2.5×10 6 myoblasts) previously expanded ex vivo for 7 days (ACE inhibitors+myoblasts, n=37). Left ventricular function was assessed by 2D echocardiography. At the end of the 2-month study, left ventricular ejection fraction (%, mean±SEM) was increased in all groups (myoblasts, 37.4±1.2; ACE inhibitors, 31.6±1.7; ACE inhibitors+myoblasts, 43.9±1.4) compared with that in control rats (19.8±0.7) ( P <0.0001). The improvement in ejection fraction was similar in the ACE inhibitor and the myoblast groups (31.6±1.7 versus 37.4±1.2, P =0.0636). However, in the ACE inhibitor+myoblast group, this improvement was greater than that seen in hearts receiving either treatment alone (43.9±1.4 versus 31.6±1.7 in the ACE inhibitor group and 43.9±1.4. versus 37.4±1.2 in the myoblast group, P <0.0001 and P =0.0084, respectively). Conclusions These data provide further support for the clinical relevance of autologous SM cell transplantation in that its cardioprotective effects are additive to those observed with ACE inhibitors.

scholarly journals Bioenergetic and Functional Consequences of Bone Marrow–Derived Multipotent Progenitor Cell Transplantation in Hearts With Postinfarction Left Ventricular Remodeling

Circulation ◽  
2007 ◽  
Vol 115 (14) ◽  
pp. 1866-1875 ◽  
Author(s):  
Lepeng Zeng ◽  
Qingsong Hu ◽  
Xiaohong Wang ◽  
Abdul Mansoor ◽  
Joseph Lee ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
Cell Transplantation ◽  
Cyclosporine A ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Infarct Zone ◽  
Ventricular Ejection Fraction ◽  
Left Anterior Descending Artery

Background— The present study examined whether transplantation of adherent bone marrow–derived stem cells, termed pMultistem, induces neovascularization and cardiomyocyte regeneration that stabilizes bioenergetic and contractile function in the infarct zone and border zone (BZ) after coronary artery occlusion. Methods and Results— Permanent left anterior descending artery occlusion in swine caused left ventricular remodeling with a decrease of ejection fraction from 55±5.6% to 30±5.4% (magnetic resonance imaging). Four weeks after left anterior descending artery occlusion, BZ myocardium demonstrated profound bioenergetic abnormalities, with a marked decrease in subendocardial phosphocreatine/ATP ( 31 P magnetic resonance spectroscopy; 1.06±0.30 in infarcted hearts [n=9] versus 1.90±0.15 in normal hearts [n=8; P <0.01]). This abnormality was significantly improved by transplantation of allogeneic pMultistem cells (subendocardial phosphocreatine/ATP to 1.34±0.29; n=7; P <0.05). The BZ protein expression of creatine kinase–mt and creatine kinase–m isoforms was significantly reduced in infarcted hearts but recovered significantly in response to cell transplantation. MRI demonstrated that the infarct zone systolic thickening fraction improved significantly from systolic “bulging” in untreated animals with myocardial infarction to active thickening (19.7±9.8%, P <0.01), whereas the left ventricular ejection fraction improved to 42.0±6.5% ( P <0.05 versus myocardial infarction). Only 0.35±0.05% donor cells could be detected 4 weeks after left anterior descending artery ligation, independent of cell transplantation with or without immunosuppression with cyclosporine A (with cyclosporine A, n=6; no cyclosporine A, n=7). The fraction of grafted cells that acquired an endothelial or cardiomyocyte phenotype was 3% and ≈2%, respectively. Patchy spared myocytes in the infarct zone were found only in pMultistem transplanted hearts. Vascular density was significantly higher in both BZ and infarct zone of cell-treated hearts than in untreated myocardial infarction hearts ( P <0.05). Conclusions— Thus, allogeneic pMultistem improved BZ energetics, regional contractile performance, and global left ventricular ejection fraction. These improvements may have resulted from paracrine effects that include increased vascular density in the BZ and spared myocytes in the infarct zone.

Injection of autologous bone marrow cells in hyaluronan hydrogel improves cardiac performance after infarction in pigs

2014 ◽  
Vol 306 (7) ◽  
pp. H1078-H1086 ◽  
Author(s):  
Chien-Hsi Chen ◽  
Ming-Yao Chang ◽  
Shoei-Shen Wang ◽  
Patrick C. H. Hsieh
Keyword(s):  
Bone Marrow ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Normal Saline ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Coronary Artery Ligation ◽  
Intramyocardial Injection ◽  
Ventricular Ejection Fraction

Intramyocardial injection of bone marrow mononuclear cells (MNCs) with hyaluronan (HA) hydrogel is beneficial to the ischemic heart in a rat model of myocardial infarction (MI). However, the therapeutic efficacy and safety must be addressed in large animals before moving onto a clinical trial. Therefore, the effect of combined treatment on MI was investigated in pigs. Coronary artery ligation was performed in minipigs to induce MI followed by an intramyocardial injection of normal saline ( n = 7), HA ( n = 7), normal saline with 1 × 108 freshly isolated MNCs ( n = 8), or HA with 1 × 108 MNCs (HA-MNC; n = 7), with a sham-operated group serving as a control ( n = 7). The response of each experimental group was estimated by echocardiography, ventricular catheterization, and histological analysis. Although injection of HA or MNCs slightly elevated left ventricular ejection fraction, the combined HA-MNC injection showed a significant increase in left ventricular ejection fraction, contractility, infarct size, and neovascularization. Importantly, injection of MNCs with HA also promoted MNC retention and MNC differentiation into vascular lineage cells in pigs. Therefore, this study not only provides evidence but also raises the possibility of using a combined HA-MNC injection as a promising therapy for heart repair.

P4535Discharge treatment with ACE inhibitor/ARB after a heart failure hospitalization is associated with a better prognosis irrespectively of left ventricular ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Vicent Alaminos ◽  
J Cinca ◽  
R Vazquez-Garcia ◽  
J R Gonzalez-Juanatey ◽  
M Rivera ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Ace Inhibitor ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Refractory Heart Failure ◽  
All Cause Mortality ◽  
Heart Failure Readmissions

Abstract Background Medical therapy could improve the prognosis of real-life patients discharged after a heart failure (HF) hospitalization. Purpose We aimed to determine the impact of discharge HF treatment on mortality and readmissions in different left ventricular ejection fraction (LVEF) groups. Methods Multicentre prospective registry in 20 Spanish hospitals. Patients were enrolled after a HF hospitalization. Results A total of 1831 patients were included (583 [31.8%] HF with reduced ejection fraction [HFrEF]; 227 [12.4%] HF with midrange ejection fraction [HFmrEF]; 610 [33.3%] HF with preserved ejection fraction [HFpEF], and 411 [22.4%] with unknown LVEF. Angiotensin-converting enzyme (ACE) inhibitors/Angiotensin II receptor blockers (ARB) at discharge were independently associated with a reduction in: i) all-cause mortality: hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.41–0.74, P<0.001, with a similar effect in the four groups; ii) mortality due to refractory HF HR 0.45, 95% CI 0.29–0.64, P<0.001, with a similar effect in the three groups with known LVEF; iii) mortality/HF admissions (HR 0.61; 95% CI: 0.50–0.74), more evident in HFrEF (HR 0.54; 95% CI: 0.38–0.78) compared to HRmEF (HR 0.64; 95% CI 0.40–1.02), orHFpEF (HR 0.70; 95% CI 0.53–0.92).Inpatients with HFrEFtriple therapy (ACE inhibitor/ARB+ betablocker+ mineralocorticoid receptor antagonist) was associated with the lowest mortality risk (HR 0.21; 95% CI: 0.08–0.57, P=0.002) compared to patients that received none of these drugs. Events according to the number of drugs – HFrEF (n=583) 0 (n=14) 1 (n=98) 2 (n=160) 3 (n=294) P Death or heart failure readmissions 10 (71.4) 58 (59.2) 66 (41.3) 106 (36.1) <0.001 All-cause mortality 9 (64.3) 28 (28.6) 31 (19.4) 36 (12.2) <0.001 Mortality due to refractory heart failure 7 (50.0) 14 (14.3) 17 (10.6) 17 (5.8) <0.001 – HFmrEF (n=227) 0 (n=18) 1 (n=57) 2 (n=81) 3 (n=65) P Death or heart failure readmissions 9 (50.0) 35 (61.4) 34 (42.0) 25 (38.5) 0.057 All-cause mortality 5 (27.8) 18 (31.6) 15 (18.5) 11 (16.9) 0.191 Mortality due to refractory heart failure 3 (16.7) 7 (12.3) 7 (8.6) 4 (6.2) 0.475 – HFpEF (n=610) 0 (n=61) 1 (n=242) 2 (n=219) 3 (n=69) P Death or heart failure readmissions 32 (52.5) 97 (40.1) 89 (40.6) 20 (29.0) 0.057 All-cause mortality 20 (32.8) 41 (16.9) 32 (14.6) 10 (14.5) 0.017 Mortality due to refractory heart failure 11 (18.0) 18 (7.4) 13 (5.9) 4 (5.8) 0.041 Outcomes according to the number of medications at discharge. Kaplan-Meier Curves for study outcomes Conclusions Discharge treatment with ACE inhibitor/ARB after a HF hospitalization is associated with a reduction in all-cause and refractory HF mortality, irrespectively of LVEF.

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