Improvement of collateral perfusion and regional function by implantation of peripheral blood mononuclear cells into ischemic hibernating myocardium.
OBJECTIVE
This study was performed to evaluate the angiogenic effect of implantation of peripheral blood mononuclear cells (PB-MNCs) compared with bone marrow mononuclear cells (BM-MNCs) into ischemic hibernating myocardium.


RESULTS
A NOGA electromechanical system was used to map the hibernating region and to inject cells. PB-MNCs and BM-MNCs contained similar levels of vascular endothelial growth factor and basic fibroblast growth factor, whereas contents of angiogenic cytokines (interleukin-1beta and tumor necrosis factor-alpha) were larger in PB-MNCs. Numbers of endothelial progenitors were approximately 500-fold higher in BM-MNCs. In BM-MNC-implanted myocardia of pigs, an increase in systolic function (ejection fraction from 33% to 52%) and regional blood flow (2.1-fold) and a reduction of the ischemic area (from 29% to 8%) were observed. PB-MNC implantation reduced the ischemic area (from 31% to 17%), the extent of which was less than that seen with BM-MNCs. In saline-implanted myocardium, the ischemic area expanded (from 28% to 38%), and systolic function deteriorated. Angiography revealed an increase in collateral vessel formation by PB-MNC or BM-MNC implantation. Capillary numbers were increased 2.6- and 1.7-fold by BM-MNC and PB-MNC implantation, respectively. BM-MNCs but not PB-MNCs were incorporated into neocapillaries.


CONCLUSIONS
Catheter-based implantation of PB-MNCs can effectively improve collateral perfusion and regional function in hibernating ischemic myocardium by its ability to mainly supply angiogenic factors and cytokines.
Kamihata
Hiroshi
H
Department of Medicine II and Cardiovascular Center, Kansai Medical University, Moriguchi, Osaka, Japan.
Matsubara
Hiroaki
H
Nishiue
Takashi
T
Fujiyama
Soichiro
S
Amano
Katsuya
K
Iba
Osamu
O
Imada
Takanobu
T
Iwasaka
Toshiji
T
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000737:chemistry / Q000502:physiology; D016026:Bone Marrow Transplantation; D002196:Capillaries / Q000737:chemistry / Q000166:cytology; D006328:Cardiac Catheterization / Q000379:methods; D019070:Cell Lineage; D017023:Coronary Angiography / Q000379:methods; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D016130:Immunophenotyping / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000502:physiology* / Q000637:transplantation*; D009200:Myocardial Contraction / Q000502:physiology*; D017202:Myocardial Ischemia / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology; D010477:Perfusion / Q000379:methods*; D020127:Recovery of Function / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D013552:Swine
D043925:Angiogenesis Inducing Agents