Angiogenic pretreatment improves the efficacy of cellular cardiomyoplasty performed with fetal cardiomyocyte implantation. Academic Article Article uri icon

Overview

MeSH

  • Animals
  • Cell Survival
  • Combined Modality Therapy
  • Disease Models, Animal
  • Exercise Tolerance
  • Male
  • Models, Cardiovascular
  • Myocardial Contraction
  • Myocardial Infarction
  • Myocardium
  • Rats
  • Rats, Inbred F344
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A

MeSH Major

  • Cardiomyoplasty
  • Cell Transplantation
  • Fetal Heart
  • Myocytes, Cardiac

abstract

  • Cell implantation into areas of myocardial infarction (cellular cardiomyoplasty) may be limited in efficacy because of the lack of blood supply to these areas of myocardium, resulting in early loss of transplanted cells. We therefore tested the hypothesis that pretreatment of infarcted myocardium with angiogenic therapy, followed by cell transplant, would be more effective than the application of either strategy alone. Fischer 344 rats underwent left coronary artery ligation and injection of an adenovirus encoding VEGF 121, an empty expression cassette control vector, or saline solution. Capillary density in the infarcted region was determined in preliminary studies. Cardiomyocytes harvested from syngeneic Fischer rat fetuses were prelabeled and then injected directly into the infarct area 3 weeks after vector administration. Exercise treadmill testing was performed 2 weeks after cell transplantation, after which a cell viability index was calculated as the number of implanted (prelabeled) nuclei divided by the number of coadministered microspheres detected in sections of implanted myocardium. Capillary density in the area of infarction was significantly greater in adenovirus encoding VEGF 121 compared with rats injected with saline solution (P =.001). The cell survival index was also greater in adenovirus encoding VEGF 121 compared with animals injected with empty expression cassette control or saline solution (P =.0045). Exercise tolerance was nearly doubled in animals receiving adenovirus encoding VEGF 121 3 weeks prior to cell implantation compared with animals receiving adenovirus encoding VEGF 121 or cells alone or those receiving adenovirus encoding VEGF 121 at the time of cell implantation (P <.001). Pretreatment of an infarcted region of the heart with angiogenic mediators such as VEGF can enhance the efficacy of cellular cardiomyoplasty, presumably by creating a more favorable environment for the survival of transplanted cells.

publication date

  • April 2004

has subject area

  • Animals
  • Cardiomyoplasty
  • Cell Survival
  • Cell Transplantation
  • Combined Modality Therapy
  • Disease Models, Animal
  • Exercise Tolerance
  • Fetal Heart
  • Male
  • Models, Cardiovascular
  • Myocardial Contraction
  • Myocardial Infarction
  • Myocardium
  • Myocytes, Cardiac
  • Rats
  • Rats, Inbred F344
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.jtcvs.2003.09.049

PubMed ID

  • 15052201

Additional Document Info

start page

  • 1041

end page

  • 9; discussion 1049-51

volume

  • 127

number

  • 4