Scintigraphic assessment of the effects of bone marrow-derived mononuclear cell transplantation combined with off-pump coronary artery bypass surgery in patients with ischemic heart disease.
Myocardial SPECT may be useful for assessment of the therapeutic effects and the mechanisms of cardiac regeneration medicine. We aimed to assess first the feasibility and the short-term safety of autologous bone marrow-derived mononuclear cell transplantation (BMCT) into the ischemic myocardium in patients who undergo off-pump coronary artery bypass surgery (OPCAB). In addition, we aimed to assess our hypothesis that the BMCT may help ameliorate myocardial perfusion in patients with ischemic heart disease (IHD) using myocardial perfusion scintigraphy.


METHODS
We performed BMCT in 10 patients with IHD during OPCAB. Cells for BMCT were collected by intraoperative bone marrow aspiration or by preoperative cellular apheresis after pretreatment with granulocyte colony-stimulating factor. After OPCAB was performed in all graftable ischemic areas, a total of 3.4 +/- 1.2 x 10(9) mononuclear cells, including 5.2 +/- 1.6 x 10(6) CD34-positive (CD34(+)) cells, were injected into ungraftable ischemic myocardial areas. Dipyridamole-stress and resting (99m)Tc myocardial SPECT was performed before and 1 mo after the procedures.


RESULTS
BMCT was performed safely in all patients. Compared with before treatment, myocardial (99m)Tc tracer uptake on the dipyridamole-stress image increased similarly in BMCT- and OPCAB-treated areas, whereas tracer accumulation at rest did not change in all myocardial areas. The improvement of myocardial perfusion was not correlated with the total number of mononuclear cells transplanted. However, it was positively correlated with the number of transplanted CD34(+) cells: (99m)Tc tracer uptake after/before BMCT (ratio) = 1.091 x (CD34(+) cell number [x10(6)])(0.074) (r(2) = 0.48, P < 0.05), although new development of coronary vessels was not documented cineangiographically. Myocardial histopathology in 2 of 3 autopsy cases revealed coronary angiogenesis in the areas corresponding to the sites of BMCT.


CONCLUSIONS
The present study demonstrates the feasibility of BMCT combined with OPCAB. This therapy improves myocardial perfusion possibly via CD34-related development of coronary microvessels.
Yaoita
Hiroyuki
H
First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
Takase
Shinya
S
Maruyama
Yukio
Y
Sato
Yoshiyuki
Y
Satokawa
Hirono
H
Hoshi
Nobuo
N
Ono
Nobutaka
N
Igari
Tsuguo
T
Ohto
Hitoshi
H
Yokoyama
Hitoshi
H
D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D003131:Combined Modality Therapy; D047549:Coronary Artery Bypass, Off-Pump / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000601:surgery*; D011182:Postoperative Care / Q000379:methods; D011379:Prognosis; D011877:Radionuclide Imaging; D016896:Treatment Outcome