Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Jun 2010
The role of cytokines and inducible nitric oxide synthase in endotoxemia-induced endothelial dysfunction.
Sepsis is characterized by a blunted vascular responses due to impairment of endothelial function. The aim of our study was to assess endothelial function and the role of cytokines and nitric oxide (NO). Endotoxin tolerance was induced in 14 healthy volunteers by intravenous injection of 2 ng.kg.d lipopolysaccharide on 5 consecutive days. ⋯ FBF showed an attenuation of ACh-induced vasodilatory response with 67% (45%-72%) 4 hours after the first LPS administration (P = 0.01) with an unchanged dose-response curve to sodium nitroprusside. This attenuation to ACh infusion did not occur in the presence of aminoguanidine (P = 0.21) and also did not occur when tolerance was present on day 5 (P = 0.45). Our data demonstrate that endothelial dysfunction caused by endotoxemia does not occur when endotoxin tolerance develops, indicated by the absence of cytokine production and during administration of selective inducible NO synthase inhibitor aminoguanidine in vivo.
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J. Cardiovasc. Pharmacol. · Jun 2010
Review Comparative StudyPreventing serious sequelae after an acute coronary syndrome: the consequences of thrombosis versus bleeding with antiplatelet therapy.
Acute coronary syndrome (ACS) is associated with a persistent prothrombotic state, placing patients at high risk of subsequent ischemic events. Guidelines recommend the use of dual antiplatelet therapy with aspirin + a thienopyridine (clopidogrel) for at least a year after ACS in most patients, except those who undergo coronary artery bypass grafting. Clinical studies demonstrate that this strategy significantly reduces the risk of ischemic events at the expense of a small increase in the risk of bleeding. ⋯ The relationship between bleeding and mortality is complicated by the fact that many risk factors for bleeding are also those for mortality and that bleeding may lead to discontinuation of antiplatelet therapy, thereby increasing the risk for an ischemic event. Data suggest that physicians tend to overestimate the risk of bleeding and underestimate the risk of ischemia. Careful patient selection and thorough patient education are the keys to managing antiplatelet therapy after ACS, especially as newer more potent antiplatelet agents, such as prasugrel, become available.