Platelets activation is associated with elevated plasma mitochondrial DNA during cardiopulmonary bypass.
BACKGROUND
Mitochondrial DNA (mtDNA) was reported as a pro-inflammatory agent. In our previous study, elevation of plasma mtDNA was revealed after cardiac surgery with cardiopulmonary bypass (CPB). Platelets were activated during the cardiac surgery and recent study revealed its ability to release mtDNA. Our present study postulated that the elevated plasma mtDNA comes from activated platelets, which plays a critical role in post-CPB inflammatory responses.


METHODS
Sixty-eight patients who underwent coronary artery bypass graft (CABG) with CPB were enrolled in our study. Blood samples were collected before induction of anaesthesia (T1), at the end of CPB (T2), 12 h post-CPB (T3), 24 h post-CPB (T4), 48 h post-CPB (T5) and 72 h post-CPB (T6). Blood samples were analyzed for the routine blood test and prepared for plasma isolation. MtDNA concentration was measured by rt-PCR, and TNF-α and IL-6 were examined by specific ELISA kits. Subgroup study was analyzed by activation levels of platelet. Basic information, mtDNA level, TNF-α level and IL-6 level were all carefully studied in each quartile.


RESULTS
Activation level of platelets increased and peaked at T2, which decreased gradually from T3 to T6 (P < 0.05). MtDNA increased after CPB, peaked at T3, and then backed from T4 to T6 (P < 0.05). Bivariate correlation between peak activation level of platelets and peak plasma mtDNA level showed a positive correlation between these two parameters (r = 0.683, P < 0.0001). Both TNF-α and IL-6 showed similar patterns as mtDNA, with an increase from T1 to T3 and a decrease from T4 to T6 (P < 0.05). Subgroup analysis further demonstrated that patients with higher activation levels of PLT had higher plasma mtDNA levels and inflammatory level (P < 0.05).


CONCLUSIONS
Our study revealed the dynamic changes of activation level of platelets and identified the interesting association between platelets activation and plasma mtDNA, suggesting a novel potential mechanism of activated platelets-induced post-CPB inflammatory responses.
Department of Cardiovascular Surgery, West China Hospital, Si Chuan University, Guo Xue Alley 37, Cheng du, Sichuan, 610041, People's Republic of China.
Chaoyi
C
Qin
Department of Cardiovascular Surgery, West China Hospital, Si Chuan University, Guo Xue Alley 37, Cheng du, Sichuan, 610041, People's Republic of China.
Jun
J
Gu
Department of Cardiovascular Surgery, West China Hospital, Si Chuan University, Guo Xue Alley 37, Cheng du, Sichuan, 610041, People's Republic of China.
Jia
J
Hu
Department of Cardiovascular Surgery, West China Hospital, Si Chuan University, Guo Xue Alley 37, Cheng du, Sichuan, 610041, People's Republic of China.
Hong
H
Qian
Department of Anesthesiology, Chengdu Women and Children's Central Hospital, Chengdu, People's Republic of China.
Xu
X
Fei
Department of Cardiology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Yajiao
Y
Li
Department of Burns and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Ruiqi
R
Liu
Department of Cardiovascular Surgery, West China Hospital, Si Chuan University, Guo Xue Alley 37, Cheng du, Sichuan, 610041, People's Republic of China. meng_wei_1111@yahoo.com.
Wei
W
Meng
D001792:Blood Platelets / Q000502:physiology*; D002315:Cardiopulmonary Bypass; D004272:DNA, Mitochondrial / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D004272:DNA, Mitochondrial; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
Cardiopulmonary bypass; Inflammation; Mitochondrial DNA; Platelets