BACKGROUND:Chronic myocardial infarction (CMI), represents a public health and a financial burden. Since stem cell transplant is used to regenerate cardiac tissue after acute myocardial infarction. AIM OF THE STUDY:To determine if autologous CXCR4 stem cells could restore damaged myocardial tissue in patients with CMI lesions. METHODS:20 NYHA grade III male patients with CMI defined by clinical, biochemical, ECG and echocardiographic parameters were included. Patients were treated with G-CSF for 6 d before isolating their autologous stem cells from PBMCs. Cell phenotyping was done by cytofluorometry using monoclonal antibodies (anti-CXCR4, -CD34, -48, -117, -133, -Ki67, -SDF1 and CXCR4); CXCR4 cell subpopulations isolated by sorting were adjusted to 1 × 108 cells by subpopulation and injected in a circular pattern into the cicatrix previously defined by echocardiography. RESULTS:Patients were followed for 6 and 12 months. Six months after cell implant improvements in left ventricle ejection fraction (from 33-50%), stress rate values (from -3/-9% to -18/-22%), stress tests (from 4-12 METS), and the quantity of left ventricle affected segments (3-9) disappeared according to the G-SPECT images. 12 months evaluations did not show significant differences. Interestingly, 3 months after cell implant the ECG showed normal electrical activity in 9 patients whereas after 6 months it was normal in all the patients. CONCLUSIONS:These results ratify that locally injected autologous CXCR4+ bone marrow-derived stem cells have a physiological and a clinical impact in patients with CMI.
Introduction: The physiological process of sternum surgical fracture consolidation in patients undergoing cardiac surgery could be prolonged by the invasion of gram-positive saprophytic bacteria which perpetuates the local inflammatory process despite the standardized aseptic and antiseptic measures in cardiac surgery. In this regard, the topical application of Vancomycin can exert a positive effect and prevent the perpetuation of the local inflammatory process by the elimination of these bacteria which in turn reduces bone consolidation time.The purpose of the current study was to determine the effect of topical Vancomycin on sternum surgical fracture consolidation in patients undergoing to open-heart surgery. Materials and Methods: Patients who underwent open heart surgery were assigned into groups receiving the topical application of bone wax or Vancomycin mass in the spongy tissue exposed by surgical sternotomy, prior to sternal closure. The bone consolidation processes were assessed by two expert radiologists with simple chest computed tomography (CT) in the postoperative period (4, 8, and 12 weeks). Results: The study was conducted on 55 patients in Vancomycin (n=33) and bone wax group (n=19). The computerized axial tomography (CAT) scan revealed a higher number of patients with early bone consolidation (Medullar and bone continuity, and callus bone) in Vancomycin group, as compared to bone wax group (p values between 0.004-0.02 at 4 weeks and 0.01-0.06 at 8 weeks). However, no difference was observed at 12 weeks (P=0.09-0.11). Moreover, The magnitude effect of topical Vancomycin was high (>90%) at 3, 8, and 12 weeks of follow up, compared to the patients who received bone wax (<90%). Conclusion: The topical Vancomycin application had a positive effect on sternal surgical fracture and promotes an early bone consolidation in patients undergoing open-heart surgery.
Cell therapy has shown beneficial effects on ventricular function and tissue regeneration in patients with acute and chronic myocardial infarction, although with diverse grades of variability in the results, possibly by proportion, subtype and cell cycle status. Objective: Identify and phenotypically characterize, via CXCR4 and SDF-1 expression, the bone marrow cell subpopulations that are mobilized into the bloodstream in patients with Acute Myocardial Infarction (AMI) and Acute Ischemia (AI) such as acute angina and Chronic Ischemia (CI) such as chronic stable angina, and also determine the cell cycle status of these cells. Method: Patients with AMI and AI were recruited in the ICCU, and patients with CI in the departments of cardiology and cardiovascular surgery. The quantification of cellular subpopulations was made by cytofluorometry with a FACS caliburcyto fluorometry (Becton Dickinson) with specific FITC-labeled anti human monoclonal antibodies against CD34, CD133, CD117, CD48, CXCR4, SDF-1 and Ki67 (Becton Dickinson). Serum concentration of IL-6 and IL-8 were determined by a sequential solid phase chemiluminescent assay performed in a SIEMENS IMMULITE 1000 Analyzer. Statistical analysis was made with the SPSS version 20.0 for Windows. A p value 3/ml) than that in AI (9.2 ± 1.3 × 103/ml) and CI (6.6 ± 1.1 × 103/ml) patients (p p = 0.22 to 0.39), but interestingly in AMI and AI patients, cells were CXCR4+ in almost half of these mobilized cells, although the proportion was significantly higher in AMI patients (46.8% ± 7.1% to 55.7% ± 6.3% vs 23% ± 1.6% to 28.4% ± 2.1%, p = 0.03 to 0.05). A similar behavior was observed with the Ki67 antibody (29.9% ± 2.1% to 36.1% ± 6.3% vs 10% ± 1.2% to 24% ± 1.1%, p = 0.001 to 0.05). Bivariate analysis of the results showed a significant correlation of the cell proportion in AMI but not in AI and CI patients (p = 0.001 to 0.05; 0.12 to 0.87 and 0.17 to 0.92 respectively). The amount of myocardial tissue infarcted did not show any correlation with the amount of cellular subpopulations mobilized to peripheral blood (r = 0.10 to 0.20; p = 0.21 to 0.64) from the bone marrow. Conclusion: The proportion of cellular subpopulations with regenerative potential mobilized to circulation during an event of Acute Myocardial Infarction is significantly higher than during an event of acute angina and chronic stable angina, with a significant proportion of mobilized cells that expressed CXCR4, most of which were already in some of the cell cycle phases.
Aims: We have shown that autologous transplant of CD34 + -enriched peripheral-blood mononuclear cells (PBMSC) could restore depressed myocardial function, and sustain adequate myocardial function 12 months after surgery in patients with old (>one yearold) myocardial infarction.Our aim is to report the long-term morbidity and mortality efficacy of this procedure.Methods and results: Seventy patients with an old anteroseptal myocardial infarction were followed for 2 to 7 years, 35 had a revascularization procedure and received an intra-myocardial injection of autologous CD34 + -enriched PBMSC (8 × 10 8 mononuclear cells/ml including 3 × 10 7 CD34 + cells/ml)(Group A).Group B patients only had the revascularization.Abnormal pre-surgical values of LVEF (33.2% ± 4.8%), LVDV (178 ± 13.7 ml), LVSV (120 ± 16 m), LVDD (58.9 ± 3.84 mm), E and A waves without contractility in infarction area in group A patients improved to approximate normal values (50% ± 3% for LVEF; 90 ± 9.3 ml for LVDV; 80 ± 9.9 ml for LVSV; 55.3 ± 3 mm for LVDD; 5.2 ± 0.5 cm/s for E wave and 4.18 ± 0.3 cm/s for A wave) 1 year after the procedure and have remained unaltered for all the follow-up period.All the patients remain alive.Only seven patients have been readmitted to the hospital for non-myocardial related events.Group B only 11 patients continued alive to 5 years after surgery and LEVF never increased more than 6%, all of them with many hospitalizations (n ≥ 10) by heart failure events.Conclusion: Intramyocardial injection of CD34 + highly enriched PBSC represent an encouraging alternative for patients with severely scarred and dysfunctional myocardium.
Introduction and objectives. Ostium secunclum atrial septal defects require closure. Echocardiographic studies have reported that, in 7% of cases, the Amplatzer occluder is orientated perpendicular to the rim of the defect. This article describes the use of an ancillary technique involving a balloon catheter that enables the Amplatzer device to be positioned transversely.Methods. We report six patients with an ostium secundum atrial septal defect in whom echocardiographic imaging showed that the Amplatzer device was positioned perpendicular to the rim of the defect. To correct the device's orientation, we used an ancillary maneuver that involved placing a balloon catheter at the device's lower edge, thereby inducing it to adopt a transverse position and undergo successful implantation.Results. In all cases, the ancillary balloon catheter technique enabled the device to adopt the correct transverse odentation, thereby facilitating successful implantation.Conclusions. The ancillary balloon catheter technique is useful for ensuring that Amplatzer devices adopt a transverse orientation when echocardiography shows the device to be persistently orientated perpendicular to the rim of the septal defect.
La comunicación interauricular ostium secundum (CIAOS) es una afección que require cierre del defecto. Se han publicado imagines ecocardiográficas con la posición perpendicular del oclusor Amplatzer en el 7% de los casos. En este documento describimos una técnica de apoyo con balón que permite la presentación transversa del dispositivo. En 6 pacientes con diagnóstico de CIAOS se observó mediante imágenes ecocardiograficas la posición perpendicular del dispositivo sobre los bordes del defecto. Para corregir esta posición, aplicamos una maniobra de apoyo con balón sobre el borde inferior del dispositivo para favorecer la posición transversa y su implantación. En todos los casos, la maniobra de apoyo con balón permitió la correcta presentación transversa del dispositivo, favoreciendo su implantación. La técnica de apoyo con balón es una alternativa útil que permite la posición transversa del dispositivo Amplatzer cuando en imágenes ecocardiográficas el dispositivo mantiene una posición persistentemente perpendicular sobre los bordes del defecto. Ostium secundum atrial septal defects require closure. Echocardiographic studies have reported that, in 7% of cases, the Amplatzer occluder is orientated perpendicular to the rim of the defect. This article describes the use of an ancillary technique involving a balloon catheter that enables the Amplatzer device to be positioned transversely. We report six patients with an ostium secundum atrial septal defect in whom echocardiographic imaging showed that the Amplatzer device was positioned perpendicular to the rim of the defect. To correct the device's orientation, we used an ancillary maneuver that involved placing a balloon catheter at the device's lower edge, thereby inducing it to adopt a transverse position and undergo successful implantation. In all cases, the ancillary balloon catheter technique enabled the device to adopt the correct transverse orientation, thereby facilitating successful implantation. The ancillary balloon catheter technique is useful for ensuring that Amplatzer devices adopt a transverse orientation when echocardiography shows the device to be persistently orientated perpendicular to the rim of the septal defect.
Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue. The first three cells lines have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, after stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation methods in infarcted myocardial tissue.
Autologous transplant of bone marrow stem cells (BMSC), although extremely useful after acute myocardial events, has not been evaluated in patients with old (>one-year-old) myocardial infarction. Our aim was to determine if CD34(+)-enriched peripheral-blood cells, obtained by apheresis, injected directly into the severely damaged myocardium of five patients with old myocardial infarction could restore depressed myocardial function. We found that 28 weeks after revascularization and peri-infarction injection of the enriched CD34(+) peripheral mononuclear cells, ventricular hemodynamic parameters that included left ventricular ejection fraction, left ventricular diastolic volume, ventricular systolic volume and left ventricular diastolic diameter approximated normal values and there was no restenosis; two patients have been followed for >52 weeks and their parameters are within normal values. In conclusion, intramyocardial injection of easily obtained CD34(+) enriched peripheral blood cells represent an encouraging procedure for patients with severely scarred and dysfunctional myocardium.
The aim of this work was to determine whether there is a pre-established basal condition of the endothelial cells isolated from aortic abdominal aneurysm that might augment immune effector mechanisms and thus provide us an insight into the possible causes of aneurysm rupture. Endothelial cells isolated from saccular aortic aneurysm fragments were analyzed by cytofluorometry for the expression of different immune response-related molecules. Our results showed that there is a subpopulation of granule-rich, CD105 positive and von Willebrand antigen negative endothelial cells that have an enhanced basal expression of ICAM-1, and Fas antigen, but, interestingly, no apoptotic bodies were detected. Control endothelial cells derived from healthy areas of the same abdominal aortas did not show such enhanced expression. We conclude that in the endothelium that lines abdominal aorta aneurysms there is, at least, one endothelial cell subpopulation with an apparent inhibition of programmed cell death and in a proinflammatory activation status.
The aim of this work was to determine whether there is a pre-established basal condition of the endothelial cells isolated from aortic abdominal aneurysm that might augment immune effector mechanisms and thus provide us an insight into the possible causes of aneurysm rupture. Endothelial cells isolated from saccular aortic aneurysm fragments were analyzed by cytofluorometry for the expression of different immune response-related molecules. Our results showed that there is a subpopulation of granule-rich, CD105 positive and von Willebrand antigen negative endothelial cells that have an enhanced basal expression of ICAM-1, and Fas antigen, but, interestingly, no apoptotic bodies were detected. Control endothelial cells derived from healthy areas of the same abdominal aortas did not show such enhanced expression. We conclude that in the endothelium that lines abdominal aorta aneurysms there is, at least, one endothelial cell subpopulation with an apparent inhibition of programmed cell death and in a proinflammatory activation status.