Association of electrostimulation with cell transplantation in ischemic heart disease

BackgroundUntil now, cell therapy has constituted a passive therapeutic approach; the only effects seem to be related to the reduction of the myocardial fibrosis and the limitation of the adverse ventricular remodeling. Cardiac resynchronization therapy is indicated in patients with heart failure to correct conduction disorders associated with chronic systolic and diastolic dysfunction. The association of electrostimulation with cellular cardiomyoplasty could be a way to transform passive cell therapy into “dynamic cellular support.” Electrostimulation of ventricles following skeletal myoblast implantation should induce the contraction of the transplanted cells and a higher expression of slow myosin, which is better adapted for chronic ventricular assistance. The purpose of this study is to evaluate myogenic cell transplantation in an ischemic heart model associated with cardiac resynchronization therapy.MethodsTwenty two sheep were included. All animals underwent myocardial infarction by ligation of 2 coronary artery branches (distal left anterior descending artery and D2). After 4 weeks, autologous cultured myoblasts were injected in the infarcted areas with or without pacemaker implantation. Atrial synchronized biventricular pacing was performed using epicardial electrodes. Echocardiography was performed at 4 weeks (baseline) and 12 weeks after infarction.ResultsEchocardiography showed a significant improvement in ejection fraction and limitation of left ventricular dilatation in cell therapy with cardiac resynchronization therapy as compared with the other groups. Viable cells were identified in the infarcted areas. Differentiation of myoblasts into myotubes and enhanced expression of slow myosin heavy chain was observed in the electrostimulated group. Transplantation of cells with cardiac resynchronization therapy caused an increase in diastolic wall thickening in the infarcted zone relative to cells-only group and cardiac resynchronization therapy–only group.ConclusionsBiventricular pacing seems to induce synchronous contraction of transplanted myoblasts and the host myocardium, thus improving ventricular function. Electrostimulation was related with enhanced expression of slow myosin and the organization of myoblasts in myotubes, which are better adapted at performing cardiac work. Patients with heart failure presenting myocardial infarct scars and indication for cardiac resynchronization therapy might benefit from simultaneous cardiac pacing and cell therapy

Normal human immunoglobulins for intravenous use (IVIg) delay hyperacute xenograft rejection through F(ab′)2-mediated anti-complement activity

Xenotransplantation between discordant species leads to a hyperacute rejection mediated by natural antibodies, both of the IgG and IgM isotypes, activation of complement and endothelial cell activation. The combination of these mechanisms leads to a transplant survival of minutes to a few hours. Polyclonal human immunoglobulins for intravenous use (IVIg) from normal donors have proved effective in a number of antibody-mediated disorders, as well as in inflammatory disorders. We demonstrate that administration of IVIg in a guinea pig to rat model of cardiac xenografting can effectively delay hyperacute rejection. This effect is mediated by the F(ab′)2 fragments of IVIg, and is correlated to an anti-complementary activity

Standardized approach to valve repair using an expansible aortic ring versus mechanical Bentall: early outcomes of the CAVIAAR multicentric prospective cohort study

International audienceOBJECTIVE: The study objective was to compare the 30-day outcomes of a standardized aortic valve repair technique (REPAIR group) associating root remodeling with an expansible aortic ring annuloplasty versus mechanical composite valve and graft (CVG group) replacement in treating aortic root aneurysms. METHODS: A total of 261 consecutive patients with aortic root aneurysm were enrolled in this multicentric prospective cohort (131 in the CVG group, 130 in the REPAIR group) in 20 centers. The main end point is a composite criterion including mortality; reoperation; thromboembolic, hemorrhagic, or infectious events; and heart failure. Secondary end points were major adverse valve-related events. Crude and propensity score adjusted estimates are provided. RESULTS: The mean age was 56.1 years, and the valve was bicuspid in 115 patients (44.7%). The median (interquartile range) preoperative aortic insufficiency grade was 2.0 (1.0-3.0) in the REPAIR group and 3.0 (2.0-3.0) in the CVG group (P = .0002). Thirty-day mortality was 3.8% (n = 5) in both groups (P = 1.00). Despite a learning curve and longer crossclamp times for valve repair (147.7 vs 99.8 minutes, P \textless .0001), the 2 groups did not differ significantly for the main criterion (odds ratio, 1.31; 95% confidence interval, 0.72-2.40; P = .38) or 30-day mortality (odds ratio, 0.99; 95% confidence interval, 0.28-3053; P = .99), with a trend toward more frequent major adverse valve-related events in the CVG group (odds ratio, 2.52; 95% confidence interval, 0.86-7.40; P = .09). At discharge, 121 patients (96.8%) in the REPAIR group had grade 0 or 1 aortic insufficiency. CONCLUSIONS: A new standardized approach to valve repair, combining an expansible aortic annuloplasty ring with the remodeling technique, presented similar 30-day results to mechanical CVG with a trend toward reducing major adverse valve-related events. Analysis of late outcomes is in process for 3- and 10-year follow-ups