Abstract 3178: Implantation of Autologus Mesenchymal Stem Cells Into Atrioventricular Annulus Improves Cardiac Conduction and Cardiac Output in Canine With Complete Heart Block
Introduction: Mesenchymal stem cells (MSCs) are capable of division, differentiation and coupling with adjacent myocytes in vitro and in vivo. Here we tested the feasibility of implanting MSCs into autologous atrioventricular (AV) annulus as an alternative treatment for complete atrioventricular block (CAVB).
Methods: MSCs were isolated from bone marrow of adult dogs. The cells were incubated and propagated in vitro. The third generation of MSCs was transfected with adenoviral constructs of green fluorescent protein (GFP) and suspended in cultural medium. CAVB was induced by radiofrequency ablation and electronic pacemaker was implanted. A thoracotomy was then performed. After the fatty tissue in right AV groove was stabilized with two forceps, 4 × 106 of MSCs (MSC group, 6 dogs) or saline (control group, 4 dogs) were injected into the right AV annular region. Animals were monitored by electrocardiogram and echocardiogram for up to 4 weeks after injection, at which time cardiac output (CO) was measured by thermodilution in pulmonary artery. The heart was then removed and the injection site was visually harvested for immunohistochemical studies.
Results: The 1:1 AV conduction was recovered in 3 dogs (50%) in MSC group with shortened P-R intervals (0.96 +/− 0.22 s, mean +/− SD) during the 4-week observation, whereas no improvement was observed in control dogs. Stroke volume was lower in MSC group than that in control group (34.3 +/− 11.1 ml/p vs. 48.3 +/− 1.7 ml/p, P<.05). CO in MSC group was higher than that in control group (2.9 +/− 0.6 L/min vs. 2.1+/−0.2 L/min, P<.05). No tachyarrhythmia or ventricular hypertrophy was observed in all dogs by echocardiography in 4 weeks. Immuno-histochemical studies identified the presence of GFP-labeled MSCs and gap junction protein connexin43 between MSCs and surrounding atrial/ventricular myocytes. No GFP-labeled MSCs were found in distal myocardium of atrium or ventricle.
Conclusions: Autograft of MSCs into AV annulus offers a promising therapeutic method for CAVB through improving cardiac conduction and cardiac output, although long-term stability and safety of the approach remain to be evaluated.