scholarly journals Commentary: Come on Maybe Lyse My Fire? Cell-Free DNA: A Potential Novel Therapeutic Target for Post-Cardiopulmonary Bypass Inflammation

Author(s):  
Paul Joseph Devlin ◽  
Sunjay Kaushal
Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Justinn Tanem ◽  
John Scott ◽  
George M Hoffman ◽  
Robert A Niebler ◽  
Aoy TOMITA-MITCHELL ◽  
...  

Introduction: Preoperative risk stratification in congenital cardiac surgery includes patient and procedure related factors, which may be used in clinical decision making as well program performance evaluation. Despite these tools, unidentified factors contribute to wide variation in outcomes both within and between centers. Identification of latent physiologic risk factors may strengthen predictive models. Hypothesis: Total cell-free DNA (TCF) functions as a biomarker for cellular injury as well as a pro-inflammatory cytokine. We hypothesized that elevated preoperative TCF would be associated with poor outcome following pediatric cardiac surgery requiring cardiopulmonary bypass (CPB). Methods: Prospective observational study of children age < 18 yr and wt > 3 kg undergoing planned CPB surgery. The Children’s Wisconsin Institutional Review Board approved the protocol . A serum TCF sample was obtained after induction of anesthesia prior to surgical incision. The primary outcome measure was a composite of postoperative cardiac arrest, ECMO, or death (CAED). Association of outcome to TCF was assessed by logistic regression with a cutpoint chosen by ROC curve exploration. Odds ratios with 95% CI were calculated. Results: Data were available in 117 patients, median age 0.9 years (range 0-17.4), median weight 7.8kg (range 3.2-98). The primary outcome (CAED) was met in 6/117 (5.1%). Table 1 summarizes characteristics of patients with and without CAED. Risk of CAED was 2% with TCF<20 ng/ml, and 27% with TCF>20 ng/ml (OR=18.2, CI 2.2- 212, p<0.01). Elevated TCF was associated to fewer hospital free days (GLM p<0.01). Data in table reported as median [IQR]. Conclusions: Preoperative TCF has an important association with postoperative cardiac arrest, ECMO, and death. Alternative or intensified treatment strategies could be considered in patients with elevated preoperative TCF.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Carolyn Weber ◽  
Alexander Jenke ◽  
Vasilena Chobanova ◽  
Mariam Yazdanyar ◽  
Agunda Chekhoeva ◽  
...  

AbstractThe use of cardiopulmonary bypass (CPB) results in the activation of leukocytes, release of neutrophil extracellular traps (NETs) and severe inflammation. We hypothesize that targeting of circulating cell-free DNA (cfDNA) by DNases might represent a feasible therapeutic strategy to limit CPB-associated side effects. Male Wistar rats (n = 24) underwent CPB with deep hypothermic circulatory arrest (DHCA) and were divided into 3 groups: control (group 1), one i.v. bolus DNase I before CPB start (group 2) and a second DNase I dose before reperfusion (group 3). We found a positive correlation between plasma cfDNA/NETs levels and compromised endothelial vasorelaxation after CPB. DNase I administration significantly diminished plasma cfDNA/NETs levels. Further, a dose-dependent improvement in endothelial function accompanied by significant reduction of circulating intercellular adhesion molecule (ICAM)-1 was observed. Rats of group 3 had significantly reduced plasma IL-6 levels and downregulated expression of adhesion molecules resulting in impaired leukocyte extravasation and reduced MPO activity in lungs. Mechanistically, digestion of NETs by DNase I significantly diminished NETs-dependent upregulation of adhesion molecules in human endothelial cells. Altogether, systemic DNase I administration during CPB efficiently reduced cfDNA/NETs-mediated endothelial dysfunction and inflammation and might represents a promising therapeutic strategy for clinical practice.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 304-OR
Author(s):  
CHANG ZENG ◽  
YING YANG ◽  
ZHOU ZHANG ◽  
CHUAN HE ◽  
WEI ZHANG ◽  
...  

Author(s):  
K. G. Avetisova ◽  
◽  
S. V. Kostyuk ◽  
E. V. Kostyuk ◽  
E. S. Ershova ◽  
...  
Keyword(s):  
Dnase I ◽  

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