title: Safety of intramyocardial injection of autologous bone marrow cells to treat myocardial ischemia in pigs.
abstract: OBJECTIVE
  The purpose of this study is to determine the potential adverse consequences of intracardiac injections of bone marrow mononuclear cells (BMCs) to facilitate the revascularization of ischemic myocardium.
  
  
  BACKGROUND
  Bone marrow mononuclear cells are used to treat heart failure, though there are few studies that evaluated the safety of BMC transplantation for chronic myocardial ischemia.
  
  
  METHODS
  The pigs received coronary ameroid constrictors to induce chronic myocardial ischemia and left ventricular dysfunction. At 4 weeks, autologous BMCs were injected intramyocardially by Boston Scientific Stiletto catheter with low-dose (10(7) cells) or high-dose BMC (10(8)). Control animals received saline. Blood samples were collected for hematological and chemical indices, including cardiac enzyme levels at regular time intervals postinfarction. At 7 weeks, animals underwent electrophysiological study to evaluate the arrhythmic potential of transplanted BMC, followed by necropsy and histopathology.
  
  
  RESULTS
  No mortalities were associated with intramyocardial delivery of BMC or saline. At Day 0, the total creatine phosphokinase (CPK) was in the normal range in all groups. All groups had significant elevations in CPK after ameroid placement, with no significant differences between groups. At 7 weeks, CPK in all groups had returned to pretreatment levels. Electrophysiological assessment revealed that one control animal had an inducible arrhythmia. No arrhythmias were induced in low- or high-dose BMC-treated pigs. There were no histopathological changes associated with BMC injection.
  
  
  CONCLUSIONS
  This study showed, in a clinically relevant large-animal model, that catheter-based intramyocardial injection of autologous BMC into ischemic myocardium is safe.
authors.affiliation: AC Therapeutics, 3155 Northwoods Place, Norcross, GA 30017, USA. tgoodchild@acrionline.org
authors.forename: Traci
authors.initials: T
authors.lastname: Goodchild
authors.forename: Wenxin
authors.initials: W
authors.lastname: Pang
authors.forename: Fernando
authors.initials: F
authors.lastname: Tondato
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cui
authors.forename: Yoritaka
authors.initials: Y
authors.lastname: Otsuka
authors.forename: Steve
authors.initials: S
authors.lastname: Frowein
authors.forename: Mark
authors.initials: M
authors.lastname: Ungs
authors.forename: Keith
authors.initials: K
authors.lastname: Robinson
authors.forename: Mark
authors.initials: M
authors.lastname: Poznansky
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chronos
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002364:Caseins / Q000009:adverse effects; D002453:Cell Cycle; D002454:Cell Differentiation; D002908:Chronic Disease; D052276:Creatine Kinase, BB Form / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D005434:Flow Cytometry; D020100:Hydrogels / Q000009:adverse effects; D017202:Myocardial Ischemia / Q000097:blood / Q000139:chemically induced / Q000401:mortality / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D011183:Postoperative Complications / Q000209:etiology; D015996:Survival Rate; D013552:Swine; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D014182:Transplantation, Autologous; D018487:Ventricular Dysfunction, Left / Q000601:surgery
chemical_list: D015415:Biomarkers; D002364:Caseins; D020100:Hydrogels; C009719:ameroid; D052276:Creatine Kinase, BB Form; D052279:Creatine Kinase, MB Form