Microvesicles with mitochondrial content are increased in patients with sepsis and associated with inflammatory responses

BACKGROUND Endothelial activation plays an important role in sepsis-mediated inflammation,but the triggering factors have not been fully elucidated.Microvesicles carrying mitochondrial content(mitoMVs)have been implicated in several diseases and shown to induce endothelial activation.AIM To explore whether mitoMVs constitute a subset of MVs isolated from plasma of patients with sepsis and contribute to endothelial activation.METHODS MVs were isolated from human plasma and characterized by confocal microscopy and flow cytometry.Proinflammatory cytokines,including interleukin(IL)-6,IL-8 and tumour necrosis factor(TNF)-α,and soluble vascular cell adhesion molecule(sVCAM)-1 were detected by ELISA.Human umbilical vein endothelial cells(HUVECs)were stimulated with the circulating MVs to evaluate their effect on endothelial activation.RESULTS MitoMVs were observed in plasma from patients with sepsis.Compared with those in healthy controls,expression of MVs,mitoMVs,proinflammatory cytokines and sVCAM-1 was increased.The number of mitoMVs was positively associated with TNF-αand sVCAM-1.In vitro,compared with MVs isolated from the plasma of healthy controls,MVs isolated from the plasma of patients with sepsis induced expression of OAS2,RSAD2,and CXCL10 in HUVECs.MitoMVs were taken up by HUVECs,and sonication of MVs significantly reduced the uptake of mitoMVs by HUVECs and expression of the above three type I IFNdependent genes.CONCLUSION MitoMVs are increased in the plasma of patients with sepsis,which induces elevated expression of type I IFN-dependent genes.This suggests that circulating mitoMVs activate the type I IFN signalling pathway in endothelial cells and lead to endothelial activation.

Impact of catheter-tissue contact force on lesion size during right ventricular outflow tract ablation in a swine model

Background:The catheter-tissue contact force(CF)is one of the significant determinants of lesion size and thus has a considerable impact on the effectiveness of ablation procedures.This study aimed to evaluate the impact of CF on the lesion size during right ventricular outflow tract(RVOT)ablation in a swine model.Methods:Twelve Guangxi Bama miniature male pigs weighing 40 to 50 kg were studied.After general anesthesia,a ThermoCool SmartTouch contact-sensing ablation catheter was introduced to the RVOT via the femoral vein under the guidance of the CARTO 3 system.The local ventricular voltage amplitude and impedance were measured using different CF levels.We randomly divided the animals into the following four groups according to the different CF levels:group A(3–9 g);group B(10–19 g);group C(20–29 g);and group D(30–39 g).Radiofrequency ablations were performed at three points in the free wall and septum of the RVOT in power control mode at 30 W for 30 s while maintaining the saline irrigation rate at 17 mL/min.At the end of the procedures,the maximum depth,surface diameter,and lesion volume were measured and recorded.A linear regression analysis was performed to determine the relationship between continuous variables.Results:A total of 72 ablation lesions were created in the RVOT of the 12 Bama pigs.The maximum depth,surface diameter,and volume of the lesions measured were well correlated with the CF(free wall:b=0.105,b=0.162,b=3.355,respectively,P<0.001;septum:b=0.093,b=0.150,b=3.712,respectively,P<0.001).The regional ventricular bipolar voltage amplitude,unipolar voltage amplitude,and impedance were weakly positively associated with the CF(b=0.065,b=0.125,and b=1.054,respectively,P<0.001).There was a significant difference in the incidence of steam pops among groups A,B,C,and D(free wall:F=7.3,P=0.032;septum:F=10.5,P=0.009);and steam pops occurred only when the CF exceeded 20 g.Trans-mural lesions were observed when the CF exceeded 10 g in the free wall,while the lesions in the septum were non-trans-mural even though the CF reached 30 g.Conclusions:CF seems to be a leading predictive factor for the size of formed lesions in RVOT ablation.Maintaining the CF value between 3 and 10 g may be reasonable and effective for creating the necessary lesion size and reducing the risk of complications,such as steam pops and perforations.