Rivaroxaban improves patency and decreases inflammation in a mouse model of catheter thrombosis.
BACKGROUND
Dysfunction of indwelling central venous catheters (CVC) due to tissue ingrowth or clotting is common. The study objective was to determine if the oral anticoagulant rivaroxaban (RIVA) improved CVC patency and inflammation in mice.


METHODS
Polyurethane catheters (0.5cm length) were placed unilaterally into the external jugular vein (EJV) of mice, which subsequently underwent daily gavage with either vehicle or RIVA (5mg/kg). CVC patency, as assessed by B-mode and Doppler ultrasound, and hematocrit were measured at 3, 7, 14 or 21days (n=8-11 mice/group/time-point). Plasma monocyte chemotactic protein-1 (MCP-1) levels were assessed by ELISA, EJV matrix metalloproteinase-9 (MMP-9) levels by western immunoblotting, and cell proliferation (anti-Ki67), macrophage infiltration (anti-MAC387) by immunostaining of EJV tissues.


CONCLUSIONS
CVC patency was significantly improved in RIVA-treated mice compared to vehicle-treated (93.8% vs. 62.9%) with the probability of patency in RIVA-treated mice being 1.5 times that in vehicle-treated (relative risk [RR], 1.50, 95% confidence interval [CI], 1.14-1.95, p=0.002). Plasma MCP-1 levels were lower in RIVA-treated mice vs. vehicle-treated at 21days (389±260 vs. 804±292ng/mL, p=0.005). Cell proliferation was less at day 7 in EJV from the RIVA-treated mice than vehicle-treated (5.0%±3.0 vs. 11.5%±3.6, p=0.0006), as were MMP-9 protein levels. There were no differences in hematocrit between vehicle and RIVA-treated groups at any time point. In conclusion, these data indicate RIVA lowers inflammation and improves CVC patency in a mouse model, supporting future studies to assess RIVA for improving CVC patency in patients.
Division of Nephrology & Hypertension, Internal Medicine, School of Medicine, University of Utah, 30 N. 1900 E. Room 4R312, Salt Lake City, UT 84132, USA. Electronic address: christi.terry@hsc.utah.edu.
Christi M
CM
Terry
Division of Nephrology & Hypertension, Internal Medicine, School of Medicine, University of Utah, 30 N. 1900 E. Room 4R312, Salt Lake City, UT 84132, USA.
Yuxia
Y
He
Division of Nephrology & Hypertension, Internal Medicine, School of Medicine, University of Utah, 30 N. 1900 E. Room 4R312, Salt Lake City, UT 84132, USA; Medicine, Veterans Affairs Salt Lake City Healthcare System, 500 Foothill Dr., 151N, Salt Lake City, UT 84108, USA.
Alfred K
AK
Cheung
D000818:Animals; D002405:Catheterization, Central Venous / Q000009:adverse effects; D062905:Central Venous Catheters / Q000009:adverse effects*; D018932:Chemokine CCL2 / Q000097:blood; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D000069552:Rivaroxaban / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D014654:Vascular Patency / Q000187:drug effects*
D018932:Chemokine CCL2; D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban
Central venous catheters; Chemokine CCL2; Inflammation; Rivaroxaban; Venous thrombosis