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32 Transradial Catheterisation: A Clinical Translational Model of Human Arterial Injury in vivo
  1. Andrew Mitchell1,
  2. Takeshi Fujisawa1,
  3. Nicholas Mills1,
  4. David Newby1,
  5. Nicholas Cruden2
  1. 1University of Edinburgh
  2. 2Edinburgh Heart Centre

Abstract

Introduction Endothelial outgrowth cells (EOC) isolated from the circulation can be expanded in culture and have major potential as a therapy for vascular regeneration, but investigation of their role in vascular repair has been limited by the lack of a safe model of arterial injury in man. We developed a GMP-compliant culture process for EOC production and characterised the functional response to vascular injury in patients undergoing transradial cardiac catheterization.

Methods Patients with stable angina (n = 50, 63.8 ± 10.8 years) undergoing transradial cardiac catheterization had an assessment of flow-mediated dilatation (FMD) in both radial arteries prior to catheterisation and at 24 h, 1, 4 and 12 weeks. Peripheral blood was obtained for the isolation and quantification of EOC, and for the development of a GMP-complaint protocol.

Results FMD was attenuated in the catheterised artery compared to the non-catheterised artery at 24 h (4.3 ± 3.4 vs. 10.7 ± 5.6, P < 0.05) and at one week (3.1 ± 4.1 vs. 7.7 ± 5.6, P < 0.05), but had recovered by 12 weeks. EOCs were obtained in 66.67% of patients (14/21) and using a GMP-compliant protocol we were able to produce 32.1 ± 11.2 × 106 cells over four weeks.

Conclusions Transradial catheterization is associated with endothelial denudation and radial artery vasomotor dysfunction, and represents an accessible and reproducible model of vascular injury in man. The development of an efficient GMP-compliant culture protocol for the manufacture of EOC will permit first-in-man clinical trials to assess whether EOCs are able to home to and incorporate at sites of vascular injury in man.

  • Endothelial progenitor cells
  • vascular injury
  • radial artery

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