title: Molecular Cardiac Surgery with Recirculating Delivery (MCARD): Procedure and Vector Transfer.
abstract: Despite progress in clinical treatment, cardiovascular diseases are still the leading cause of morbidity and mortality worldwide. Therefore, novel therapeutic approaches are needed, targeting the underlying molecular mechanisms of disease with improved outcomes for patients. Gene therapy is one of the most promising fields for the development of new treatments for the advanced stages of cardiovascular diseases. The establishment of clinically relevant methods of gene transfer remains one of the principal limitations on the effectiveness of gene therapy. Recently, there have been significant advances in direct and transvascular gene delivery methods. The ideal gene transfer method should be explored in clinically relevant large animal models of heart disease to evaluate the roles of specific molecular pathways in disease pathogenesis. Characteristics of the optimal technique for gene delivery include low morbidity, an increased myocardial transcapillary gradient, esxtended vector residence time in the myocytes, and the exclusion of residual vector from the systemic circulation after delivery to minimize collateral expression and immune response. Here we describe myocardial gene transfer techniques with molecular cardiac surgery with recirculating delivery in a large animal model of post ischemic heart failure.
authors.affiliation: Cardiovascular Research Center, Icahn school of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1030, New York, NY, 10029-6574, USA. michael.katz1@mssm.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katz
authors.affiliation: Cardiovascular Research Center, Icahn school of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1030, New York, NY, 10029-6574, USA.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fargnoli
authors.affiliation: Sanger Heart and Vascular Institute, Charlotte, NC, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Kendle
authors.affiliation: Cardiovascular Research Center, Icahn school of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1030, New York, NY, 10029-6574, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Bridges
mesh_terms: D000818:Animals; D006348:Cardiac Surgical Procedures / Q000379:methods*; D003331:Coronary Vessels / Q000473:pathology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000378:metabolism*; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery; D011182:Postoperative Care; D011300:Preoperative Care; D012756:Sheep
keywords: Cardiopulmonary bypass vector transfer; Gene therapy; Ischemic heart failure; Molecular cardiac surgery with recirculating delivery; Myocardial infarction; Surgical gene delivery methods