Suppression of right ventricular hypertrophy after extensive pulmonary resection in rats by granulocyte colony-stimulating factor.
BACKGROUND
The objective of the present study was to investigate the effects of granulocyte colony-stimulating factor (G-CSF) on right ventricular hypertrophy following extensive pulmonary resection in rats.


METHODS
Adult rats were divided into four groups: (1) Group S (right thoracotomy only); (2) Group L (right three lobectomy); (3) Group LG10 (Group L+G-CSF [10microg/kg/d]); and (4) Group LG100 (Group L+G-CSF [100microg/kg/d]). At postoperative day 21, weight ratio of the right ventricular to the left ventricle plus septum (RV/LV+S, indicator of right ventricular hypertrophy) were measured, and a histopathological study was conducted to determine percentage wall thickness of peripheral pulmonary arteries and proliferating cell nuclear antigen labeling index (indicator of oxidative DNA damage) of right ventricles.


RESULTS
Mean RV/LV+S for Group S was 0.27+/-0.02, significantly smaller than that for the lobectomy groups (Group L, LG10, LG100; 0.47+/-0.05, 0.35+/-0.02, 0.38+/-0.05). G-CSF significantly suppressed right ventricular hypertrophy. Mean medial wall thickness of peripheral pulmonary arteries for Group S was 13.6% +/- 4.9%, significantly smaller than that for Group L (22.9% +/- 9.6%). Compared with Group L, G-CSF reduced medial wall thickness (LG10, 17.6% +/- 9.5%; LG100, 18.0% +/- 11.2%). Incidence of proliferating cell nuclear antigen positive nuclei for Group S was 1.07% +/- 0.49%, significantly smaller than that for Group L (13.77% +/- 5.87%). G-CSF significantly reduced the incidence of proliferating cell nuclear antigen positive nuclei (LG10, 4.04% +/- 2.14%; LG100, 3.18% +/- 1.66%).


CONCLUSIONS
G-CSF administration not only reduce medial wall thickness of peripheral pulmonary arteries but also directly protect cardiomyocytes of the right ventricle, thus suppressing right ventricular hypertrophy. These results suggest that low-dose G-CSF administration can prevent right heart failure following extensive pulmonary resection.
Matsumoto
Shinsuke
S
Department of General and Cardiothoracic Surgery, Graduate School of Medicine, Gifu University, Gifu, Japan. kurt@xj8.so-net.ne.jp
Iwata
Hisashi
H
Shirahashi
Koyo
K
Saio
Masanao
M
Umeda
Yukio
Y
Marui
Tsutomu
T
Ishida
Narihiro
N
Kimura
Masaki
M
Sugimoto
Takuya
T
Manabe
Hideaki
H
Takemura
Hirofumi
H
D000818:Animals; D038481:Anterior Temporal Lobectomy / Q000401:mortality; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006454:Hemoglobins / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000209:etiology / Q000601:surgery; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000209:etiology / Q000601:surgery*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000254:growth & development / Q000473:pathology / Q000601:surgery*; D008297:Male; D032342:Muscle Cells / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013908:Thoracotomy
D006454:Hemoglobins; D018809:Proliferating Cell Nuclear Antigen; D016179:Granulocyte Colony-Stimulating Factor