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Rivaroxaban improves patency and decreases inflammation in a mouse model of catheter thrombosis.

ABSTRACT: 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.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.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.

SUBMITTER: Terry CM

PROVIDER: S-EPMC4980169 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Rivaroxaban improves patency and decreases inflammation in a mouse model of catheter thrombosis.

Terry Christi M CM He Yuxia Y Cheung Alfred K AK

Thrombosis research 20160609

<h4>Introduction</h4>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.<h4>Materials and methods</h4>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 ...[more]

PMID: 27318247

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Project description:BackgroundCentral venous catheters (CVCs) facilitate the administration of intravenous drugs, fluids, blood products and parenteral nutrition to patients with either chronic disease or critical illness. Despite a pivotal role within medical management, a common complication associated with CVC use is occlusion of the CVC lumen(s). CVC occlusion can interrupt and cause serious delays in administration of treatment interventions.ObjectivesThe primary objective of this review was to assess the efficacy and safety of different interventions used to restore patency of occluded CVC lumens, in adults and children.Search methodsWe identified trials by searching the Cochrane Central Register of Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue 9); OvidSP MEDLINE (1950 to September 2011); OvidSP EMBASE (1980 to September 2011) and NHS Evidence CINAHL (1982 to September 2011). We also searched clinical trial registers, handsearched reference lists, contacted pharmaceutical companies and authors of publications that met the inclusion criteria to identify trials.Selection criteriaWe selected randomized controlled trials which investigated the efficacy of an intervention (chemical, surgical or drug) used to restore patency to an occluded CVC lumen, in either adults or children.Data collection and analysisThree authors independently assessed those studies that met the inclusion criteria for quality and extracted the relevant data using a standardized form.Main resultsNo studies were found that investigated the efficacy and safety of either chemical or surgical interventions.Seven studies (eight papers) with a total of 632 participants were identified from the search. They investigated different comparisons, strengths of thrombolytic or anticoagulant drug interventions for treating CVC lumen occlusion thought to be caused by a thrombus.There was low quality evidence from a meta-analysis of two studies suggesting that urokinase (various strengths) was more effective than placebo for restoring patency to occluded CVC lumens in adults and children with underlying medical conditions (relative risk (RR) 2.09, 95% confidence interval (CI) 1.47 to 2.95), with a number needed to treat of 4 (95% CI 2 to 8). There was insufficient evidence to draw conclusions on the safety of urokinase.The overall quality of the evidence provided by these studies was low to very low due to one or more domains being assessed as either at 'unclear risk of bias' or 'high risk of bias'. Furthermore, the total number of participants in these studies was small and consequently may lead to spurious results.Authors' conclusionsThere is inadequate evidence to draw strong conclusions on the efficacy or safety of the drug interventions included in this review. There is some low quality evidence from a meta-analysis of two studies investigating urokinase (various strengths) and some very low evidence from two single studies investigating alteplase 2 mg/2 mL that suggest that these two drug interventions may be effective in treating withdrawal or total occlusion of CVC lumens caused by thrombosis. Further high quality, sufficiently powered research is still required to look at the efficacy and safety of urokinase, alteplase and other chemical, surgical and drug interventions for treating CVC lumen occlusion. Research studies which exclusively include child participants are especially warranted.

Project description:IntroductionCongenital muscular dystrophy is a distinct group of diseases presenting with weakness in infancy or childhood and no current therapy. One form, MDC1A, is the result of laminin alpha-2 deficiency and results in significant weakness, respiratory insufficiency and early death. Modification of apoptosis is one potential pathway for therapy in these patients.Methodsdy(2J) mice were treated with vehicle, 0.1 mg/kg or 1 mg/kg of omigapil daily via oral gavage over 17.5 weeks. Untreated age matched BL6 mice were used as controls. Functional, behavioral and histological measurements were collected.Resultsdy(2J) mice treated with omigapil showed improved respiratory rates compared to vehicle treated dy(2J) mice (396 to 402 vs. 371 breaths per minute, p<0.03) and similar to control mice. There were no statistical differences in normalized forelimb grip strength between dy(2J) and controls at baseline or after 17.5 weeks and no significant differences seen among the dy(2J) treatment groups. At 30-33 weeks of age, dy(2J) mice treated with 0.1 mg/kg omigapil showed significantly more movement time and less rest time compared to vehicle treated. dy(2J) mice showed normal cardiac systolic function throughout the trial. dy(2J) mice had significantly lower hindlimb maximal (p<0.001) and specific force (p<0.002) compared to the control group at the end of the trial. There were no statistically significant differences in maximal or specific force among treatments. dy(2J) mice treated with 0.1 mg/kg/day omigapil showed decreased percent fibrosis in both gastrocnemius (p<0.03) and diaphragm (p<0.001) compared to vehicle, and in diaphragm (p<0.013) when compared to 1 mg/kg/day omigapil treated mice. Omigapil treated dy(2J) mice demonstrated decreased apoptosis.ConclusionOmigapil therapy (0.1 mg/kg) improved respiratory rate and decreased skeletal and respiratory muscle fibrosis in dy(2J) mice. These results support a putative role for the use of omigapil in laminin deficient congenital muscular dystrophy patients.

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Rivaroxaban improves patency and decreases inflammation in a mouse model of catheter thrombosis.

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Rivaroxaban improves patency and decreases inflammation in a mouse model of catheter thrombosis.

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