학술대회안내사전등록초록등록안내초록등록/관리숙박 및 교통
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Short-term Granulocyte-Colony Stimulating Factor Treatment Dose Not Induce Endothelial Dysfunction in Patients with Myocardial Infarction
서울대학교 의과대학 내과학 교실¹ ; 서울대학교병원 임상의학연구소 심혈관 연구실² ; 서울대학교병원 심혈관센터
신정임¹ ² ³, 조현재¹ ² ³ , 김대희² , 박옥이¹ ³ , 이춘수² , 허진² , 강현재¹ ² ³ , 구본권¹ ² ³ , 김효수¹ ² ³, 손대원¹ ² ³ , 오병희¹ ² ³, 이명묵¹ ² ³, 박영배¹ ² ³, 최윤식¹ ² ³ , 김용진¹ ² ³
Background We, recently, reported that granulocyte-colony stimulating factor(G-CSF) could be used as a stem cell mobilizer to enhance myocardial regeneration in patients with myocardial infarction(MI). However, it has remained controversial whether G-CSF may induce harmful systemic inflammation, which impairs endothelial function and transiently increases the risk of cardiovascular event. Therefore, we evaluated the influence of stem cell mobilization on endothelial dysfunction and inflammation.
Methods and Results We injected G-CSF(10μg/kg/day) for 3 days in patients with acute, old MI, and healthy volunteers, as a part of ongoing stem cell clinical trial(MAGIC cell trial, the effect of intracoronary infusion of peripheral blood stem cells mobilized with G-CSF). Endothelial function was assessed by high-resolution brachial artery ultrasound before and after G-CSF. Flow-mediated dilation(FMD) during reactive hyperemia was defined as the % change in arterial diameter following 5-min arterial occlusion. WBC count, C-reactive protein(CRP), Interleukin-6(IL-6) were measured as biomarkers of inflammation. G-CSF resulted in significant elevation in WBC count in all groups. Serum levels of CRP and IL-6 increased in patients with old MI, and healthy group, however, FMD did not decrease after G-CSF. Most importantly, G-CSF did not increase serum levels of CRP and IL-6, also did not decrease FMD in patients with acute MI(see Table 1). The change of FMD after G-CSF was associated with change of serum levels of CRP(r=-0.688, p<0.001).
Conclusions Despite marked leukocytosis, endothelial function was not deteriorated by short-term G-CSF treatment. This finding suggests that G-CSF may be used safely in patients with MI.

Table 1. Comparion of FMD and inflammatory markers, before and after G-CSF treatment.

 

AMI (n=11)

OMI (n=16)

Healthy volunteer (n=12)

before

after

p-value

before

after

p-value

before

after

p-value

FMD(%)

6.97±4.06

9.25±5.62

0.169

8.47±5.47

6.24±5.44

0.12

13.39±5.24

13.20±5.54

0.722

WBC count (x103/)

7.41±2.10

42.77±19.49

0.003

6.87±1.63

33.14±6.36

<0.001

5.27±0.88

37.96±8.92

0.002

CRP (mg/dl)

1.25±0.65

0.85±0.52

0.005

0.52±0.37

1.09±0.58

0.002

0.03±0.06

0.49±0.28

0.002

IL-6 (pg/ml)

28.92±19.13

13.49±7.61

0.04

17.56±17.44.

27.04±22.51

0.023

7.43±14.41

13.50±14.72

0.012



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