Current vascular pharmacology
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Curr Vasc Pharmacol · Sep 2012
ReviewCrosstalk between inflammation and coagulation: the lessons of sepsis.
Sepsis results in the concurrent activation of inflammatory and procoagulant pathways. Bacterial products and proinflammatory cytokines trigger the coagulation system primarily via induction of tissue factor. During sepsis, activation of coagulation is accompanied by impaired function of major anticoagulant mechanisms, including antithrombin, the protein C system and fibrinolysis. ⋯ Recombinant APC protects against mortality in experimental endotoxemia and sepsis by effects that can be mediated by either EPCR - PAR1 dependent (endothelial cells, dendritic cells) or CD11b/CD18 - PAR1 dependent (macrophages) mechanisms. These protective APC effects do not rely on the anticoagulant properties of this protein. APC mutants that lack anticoagulant properties but retain the capacity to activate PAR1 are promising new drugs for sepsis treatment.
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Ticagrelor is a new oral antagonist of the platelet P2Y₁₂ receptor that offers several potential advantages compared to clopidogrel including faster and more effective inhibition of platelet aggregation. Ticagrelor has been compared to clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial in a broad population of patients with acute coronary syndrome showing a reduction of the 12-month risk of death from vascular causes, myocardial infarction and stroke without increasing the overall risk of major bleeding. In a subanalysis of the PLATO trial focusing on patients with ST-elevation myocardial infarction, ticagrelor results were consistent with those of the overall trial. Additionally, possible pleiotropic effects of ticagrelor, including an appealing interaction with adenosine, might constitute a specific advantage in this particular subset of patients.
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Curr Vasc Pharmacol · Mar 2011
ReviewPleiotropic effects of ARB in vascular metabolism--focusing on atherosclerosis-based cardiovascular disease.
The renin-angiotensin system (RAS) plays an essential role in fluid and electrolyte homeostasis and the regulation of vascular tone; however, dysregulation and over-activation of the RAS lead to the pathogenesis of various cardiovascular diseases. The RAS is closely associated with NADPH oxidase, a major enzymatic source of reactive oxygen species (ROS) in vasculature, and angiotensin II, the final effecter of the RAS, is a potent stimulator of this oxidase. There are accumulating evidences to support the significance of NADPH oxidase in the pathogenesis of atherosclerosis. ⋯ However, this group of agents exerts a wide variety of biological effects on vascular metabolism, including antioxidative and anti-inflammatory actions. These pleiotropic actions play a role in cardiovascular protection. From a viewpoint of oxidative stress, we discuss pleiotropic effects of ARBs on vascular metabolism focusing on pathogenesis of atherosclerosis-based cardiovascular diseases.
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Curr Vasc Pharmacol · Jan 2011
ReviewTotal knee replacement and chemical thromboprophylaxis: current evidence.
Thromboembolic disease remains one of the most devastating and potentially lethal complications after elective total knee replacement (TKR) surgery. Studies have shown that 40-85% of patients undergoing TKR will develop venographically confirmed deep vein thrombosis (DVT) if they are not given any type of post-operative thromboprophylaxis and approximately 0.1 to 1.7% will suffer fatal pulmonary embolism (PE). ⋯ Clinical guidelines as described by the American Academy of Orthopaedic Surgeons (AAOS), the American College of Chest Physicians (ACCP) and the UK's National Institute for Health and Clinical Excellence (NICE) are summarized along with the differences between the recommendations. The results of the new oral anticoagulants are reviewed as well as the most recent developments in the search for the most effective venous thromboembolism (VTE) prophylaxis after TKR surgery.
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Curr Vasc Pharmacol · Jan 2011
ReviewPerioperative thromboprophylaxis and anticoagulation in patients undergoing non-cardiac vascular surgery.
Patients undergoing non-cardiac vascular surgery (NCVS) are at high risk of developing perioperative venous and arterial thrombotic complications. Effective thromboprophylaxis is an essential part of the perioperative management of patients undergoing surgical procedures. ⋯ Very few of these recommendations are designed specifically for patients undergoing NCVS. This review aims to highlight the relevant guidelines and novel recommendations that are available for patients undergoing NCVS while noting their limitations and providing suggestions for specific subsets.