Rivaroxaban improves vascular response in LPS-induced acute inflammation in experimental models.

Rivaroxaban (RVX) was suggested to possess anti-inflammatory and vascular tone modulatory effects. The goal of this study was to investigate whether RVX impacts lipopolysaccharide (LPS)-induced acute vascular inflammatory response. Male rats were treated with 5 mg/kg RVX (oral gavage) followed by 10 mg/kg LPS i.p injection. Circulating levels of IL-6, MCP-1, VCAM-1, and ICAM-1 were measured in plasma 6 and 24 hours after LPS injection, while isolated aorta was used for gene expression analysis, immunohistochemistry, and vascular tone evaluation. RVX pre-treatment significantly reduced LPS mediated increase after 6h and 24h for IL-6 (4.4±2.2 and 2.8±1.7 fold), MCP-1 (1.4±1.5 and 1.3±1.4 fold) VCAM-1 (1.8±2.0 and 1.7±2.1 fold). A similar trend was observed in the aorta for iNOS (5.5±3.3 and 3.3±1.9 folds reduction, P<0.01 and P<0.001, respectively), VCAM-1 (1.3±1.2 and 1.4±1.3 fold reduction, P<0.05), and MCP-1 (3.9±2.2 and 1.9±1.6 fold reduction, P<0.01). Moreover, RVX pre-treatment, improved LPS-induced PE contractile dysfunction in aortic rings (Control vs LPS, Emax reduction = 35.4 and 31.19%, P<0.001; Control vs LPS+RVX, Emax reduction = 10.83 and 11.48%, P>0.05, respectively), resulting in 24.5% and 19.7% change in maximal constriction in LPS and LPS+RVX respectively. These data indicate that RVX pre-treatment attenuates LPS-induced acute vascular inflammation and contractile dysfunction.

Pharmacotherapy Evaluation and Utilization in Coronary Artery Bypass Grafting Patients in Kosovo during the Period 2016-2017.

BACKGROUND: Coronary Artery Bypass Grafting (CABG) is realised in patients with critical or advanced disease of coronary arteries. There are different pharmacotherapeutic approaches which are used as management, treatment and preventive therapy in cardiovascular disease or related comorbidities. Performing a successful surgery, pharmacotherapy, and increase of bypass patency rate remains a serious challenge. AIM: This study aims to analyse the patient characteristics undergoing CABG and evaluation of their drug utilisation rate and daily dosages in the perioperative period. MATERIAL AND METHODS: Data were collected from 102 patients in the period 2016-2017 and detailed therapeutic prescription and dosages, patient characteristics were analysed before the operation, after the operation and visit after operation in the Clinic of Cardiac surgery-University Clinical Center of Kosovo. RESULTS: Our findings had shown that patients provided to have normal biochemical parameters in the clinic before the operation, and were related to cardiovascular diseases and comorbidities and risk factors with mainly elective intervention. The, however, higher utilisation of cardiovascular drugs such as beta blockers, diuretics, anticoagulants, statins and lower calcium blockers, ACEi, ARBs, hydrochlorothiazide, amiodarone were founded. ARBs, beta blockers, statins, nitrates and nadroparin utilisation decreased after operation and visit after the operation, whereas amiodarone only in the visit after the operation. Diuretics are increased after the operation which decreases in the visit after the operation. Regarding the daily dosage, only metoprolol was increased in the visit after operation (P < 0.001) and visit after operation (P < 0.05) whereas losartan and furosemide were increased (P < 0.01) and (P < 0.05) respectively. CONCLUSION: The study showed that beta blockers, statins, aspirin, nitrates (before the operation), furosemide and spironolactone are the most utilised drugs. However, we found low utilisation rate for ACEi, ARBs, clopidogrel, nadroparin, warfarin, xanthines, amiodarone, calcium blockers. Daily dosages were different compared to before CABG only in metoprolol, losartan, and furosemide.

Arctigenin improves vascular tone and decreases inflammation in human saphenous vein.

The goal of this study was to test the effects of bioactive phenylpropanoid dibenzylbutyrolactone lignan arctigenin (ATG) in vascular tone. Human bypass graft vessel, from a saphenous vein (SV), were set up in organ bath system and contracted with potassium chloride (KCl, 40mM). Two concentration-response curves of noradrenaline (NE) (10nM-100µM) separated with an incubation period of 30min without (Control) or with ATG (3-100µM) were established. Inhibitors of nitric oxide, prostaglandins, K+ related channels or calcium influx were used to delineate the molecular mechanisms beyond ATG effects. To investigate anti-inflammatory actions, SV were treated with 10µM or 100µM ATG and incubated for 18h in the absence or presence of both interleukin-1beta (IL-1ß) and lipopolysaccharide (LPS) to mimic the physiological or inflamed tissue conditions. Proatherogenic and inflammatory mediators Interleukine-1 beta (IL-1ß), Monocyte Chemoattractant Proteine-1 (MCP-1), Tumor Necrosis Factor- α (TNF-α), Interleukine-6 (IL-6), Prostaglandin E2 (PGE2) and Interleukine-8 (IL-8) in the supernatant were measured. ATG significantly decreased vascular contractile response to NE. Moreover, it reduced contractions induced by KCl and cumulative addition of CaCl2. The mediators were significantly increased in inflammatory conditions compared to normal conditions, an effect which was inhibited by ATG (10 and 100µM). ATG reduces contractions in SV and decreases the production of proinflammatory-proatherogenic mediators, setting the stage for further evaluating the effect of ATG in cardiovascular diseases.