Randomized transcoronary delivery of CD34(+) cells with perfusion versus stop-flow method in patients with recent myocardial infarction: Early cardiac retention of ⁹⁹(m)Tc-labeled cells activity

J Nucl Cardiol. 2011 Feb;18(1):104-16. doi: 10.1007/s12350-010-9326-z. Epub 2010 Dec 14.

Abstract

Background: For transcoronary progenitor cells' administration, injections under flow arrest (over-the-wire balloon technique, OTW) are used universally despite lack of evidence for being required for cell delivery or being effective in stimulating myocardial engraftment. Flow-mediated endothelial rolling is mandatory for subsequent cell adhesion and extravasation.

Methods: To optimize cell directing toward the coronary endothelium under maintained flow, the authors developed a cell-delivery side-holed perfusion catheter (PC). Thirty-four patients (36-69 years, 30 men) with primary stent-assisted angioplasty-treated anterior MI (peak TnI 151 [53-356]ng/dL, mean[range]) were randomly assigned to OTW or PC autologous ⁹⁹Tc-extametazime-labeled bone marrow CD34(+) cells (4.34 [0.92-7.54] × 10⁶) administration at 6-14 days after pPCI (LVEF 37.1 [24-44]%). Myocardial perfusion (⁹⁹(m)Tc-MIBI) and labeled cells' activity were evaluated (SPECT) at, respectively, 36-48 h prior to and 60 min after delivery.

Results: In contrast to OTW coronary occlusions, no intolerance or ventricular arrhythmia occurred with PC cells' administration (P < .001). One hour after delivery, 4.86 [1.7-7.6]% and 5.05 [2.2-9.9]% activity was detected in the myocardium (OTW and PC, respectively, P = .84). Labeled cell activity was clearly limited to the (viable) peri-infarct zone in 88% patients, indicating that the infarct core zone may be largely inaccessible to transcoronary-administered cells.

Conclusions: Irrespective of the transcoronary delivery method, only ≈ 5% of native (i.e., non-engineered) CD34(+) cells spontaneously home to the injured myocardium, and cell retention occurs preferentially in the viable peri-infarct zone. Although the efficacy of cell delivery is not increased with the perfusion method, by avoiding provoking ischemic episodes PC offers a rational alternative to the OTW delivery.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cardiac Catheterization / methods*
  • Cell Tracking / methods*
  • Female
  • Frizzled Receptors / immunology
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Male
  • Myocardial Infarction / diagnostic imaging*
  • Myocardial Infarction / surgery*
  • Myocardial Perfusion Imaging / methods*
  • Radiopharmaceuticals
  • Receptors, G-Protein-Coupled / immunology
  • Staining and Labeling / methods
  • Technetium* / pharmacokinetics
  • Tomography, Emission-Computed, Single-Photon / methods
  • Treatment Outcome

Substances

  • FZD9 protein, human
  • Frizzled Receptors
  • Radiopharmaceuticals
  • Receptors, G-Protein-Coupled
  • Technetium