title: Exogenous connexin43-expressing autologous skeletal myoblasts ameliorate mechanical function and electrical activity of the rabbit heart after experimental infarction.
abstract: Acute myocardial infarction is one of the major causes of mortality worldwide. For regeneration of the rabbit heart after experimentally induced infarction we used autologous skeletal myoblasts (SMs) due to their high proliferative potential, resistance to ischaemia and absence of immunological and ethical concerns. The cells were characterized with muscle-specific and myogenic markers. Cell transplantation was performed by injection of cell suspension (0.5 ml) containing approximately 6 million myoblasts into the infarction zone. The animals were divided into four groups: (i) no injection; (ii) sham injected; (iii) injected with wild-type SMs; and (iv) injected with SMs expressing connexin43 fused with green fluorescent protein (Cx43EGFP). Left ventricular ejection fraction (LVEF) was evaluated by 2D echocardiography in vivo before infarction, when myocardium has stabilized after infarction, and 3 months after infarction. Electrical activity in the healthy and infarction zones of the heart was examined ex vivo in Langendorff-perfused hearts by optical mapping using di-4-ANEPPS, a potential sensitive fluorescent dye. We demonstrate that SMs in the coculture can couple electrically not only to abutted but also to remote acutely isolated allogenic cardiac myocytes through membranous tunnelling tubes. The beneficial effect of cellular therapy on LVEF and electrical activity was observed in the group of animals injected with Cx43EGFP-expressing SMs. L-type Ca(2+) current amplitude was approximately fivefold smaller in the isolated SMs compared to healthy myocytes suggesting that limited recovery of LVEF may be related to inadequate expression or function of L-type Ca(2+) channels in transplanted differentiating SMs.
authors.affiliation: Institute of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Ieva
authors.initials: I
authors.lastname: Antanavičiūtė
authors.forename: Eglė
authors.initials: E
authors.lastname: Ereminienė
authors.forename: Vaidas
authors.initials: V
authors.lastname: Vysockas
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Račkauskas
authors.forename: Vilius
authors.initials: V
authors.lastname: Skipskis
authors.forename: Kristina
authors.initials: K
authors.lastname: Rysevaitė
authors.forename: Rimantas
authors.initials: R
authors.lastname: Treinys
authors.forename: Rimantas
authors.initials: R
authors.lastname: Benetis
authors.forename: Jonas
authors.initials: J
authors.lastname: Jurevičius
authors.forename: Vytenis A
authors.initials: VA
authors.lastname: Skeberdis
mesh_terms: D000200:Action Potentials; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D002450:Cell Communication; D049109:Cell Proliferation; D002470:Cell Survival; D058948:Cell Tracking / Q000379:methods; D002478:Cells, Cultured; D018920:Coculture Techniques; D018031:Connexin 43 / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006329:Heart Conduction System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000378:metabolism; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D020127:Recovery of Function; D012038:Regeneration; D013318:Stroke Volume; D013997:Time Factors; D014162:Transfection; D016277:Ventricular Function, Left; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D020746:Calcium Channels, L-Type; D018031:Connexin 43; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: 2D echocardiography; autologous skeletal myoblast transplantation; connexin43; intercellular communication; myocardial infarction; optical mapping