title: Intramyocardial injection of autologous bone marrow cells as an adjunctive therapy to incomplete myocardial revascularization--safety issues.
abstract: OBJECTIVE
  To determine the safety of intramyocardial injection of autologous bone marrow cells in patients undergoing surgical myocardial revascularization (CABG) for severe coronary artery disease.
  
  
  BACKGROUND
  There is little data available regarding the safety profile of autologous bone marrow cells injected during surgical myocardial revascularization. Potential risks include arrythmias, fibrosis in the injected sites and growth of non-cardiac tissues.
  
  
  METHODS
  Ten patients (eight men) were enrolled; they were 59+/-5 years old with limiting angina and were non-optimal candidates for complete CABG. Bone marrow cells (1.3+/-0.3x10(8)) were obtained prior to surgery, and the lymphomonocytic fraction (CD34+ =1.8+/-0.3%) was separated by density gradient centrifugation. During surgery, bone marrow cells were injected in non-grafted areas of ischemic myocardium. During the first year after surgery, the patients underwent laboratory tests, cardiac imaging, and 24-hour ECG monitoring.
  
  
  RESULTS
  Injected segments: inferior (n=7), anterior (n=2), septal (n=1), apical (n=1), and lateral (n=1) walls. Except for a transient elevation of C-reactive protein at one month post-surgery (P=0.01), laboratory tests results were within normal ranges; neither complex arrhythmias nor structural abnormalities were detected during follow-up. There was a reduction in functional class of angina from 3.6+/-0.8 (baseline) to 1.2+/-0.4 (one year) (P<0.0001). Also, patients had a significant decrease in the ischemic score assessed by magnetic resonance, not only globally from 0.65+/-0.14 (baseline) to 0.17+/-0.05 (one year) (P=0.002), but also in the injected areas from 1.11+/-0.20 (baseline) to 0.34+/-0.13 (one year) (P=0.0009).
  
  
  CONCLUSIONS
  Intramyocardial injection of bone marrow cells combined with CABG appears to be safe. Theoretical concerns with arrhythmias and/or structural abnormalities after cell therapy were not confirmed in this safety trial.
authors.affiliation: Heart Institute, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. luis.gowdak@incor.usp.br
authors.forename: Luís Henrique W
authors.initials: LH
authors.lastname: Gowdak
authors.forename: Isolmar T
authors.initials: IT
authors.lastname: Schettert
authors.forename: Eduardo
authors.initials: E
authors.lastname: Baptista
authors.forename: Nailú L G
authors.initials: NL
authors.lastname: Lopes
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Rochitte
authors.forename: Marcelo Luiz C
authors.initials: ML
authors.lastname: Vieira
authors.forename: César José
authors.initials: CJ
authors.lastname: Grupi
authors.forename: Luiz Antonio M
authors.initials: LA
authors.lastname: César
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Sérgio A
authors.initials: SA
authors.lastname: de Oliveira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000601:surgery; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000401:mortality; D004452:Echocardiography; D004812:Epidemiologic Methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000601:surgery*; D009204:Myocardial Revascularization / Q000379:methods*; D018919:Neovascularization, Physiologic; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers