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.
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J. Cardiovasc. Pharmacol. · Apr 2010
Hyperglycemia inhibits anesthetic-induced postconditioning in the rabbit heart via modulation of phosphatidylinositol-3-kinase/Akt and endothelial nitric oxide synthase signaling.
Hyperglycemia is known to inhibit ischemic and anesthetic preconditioning. We tested whether hyperglycemia inhibits anesthetic postconditioning with isoflurane and whether this effect is mediated via phosphatidylinositol-3-kinase/Akt and nitric oxide signaling. New Zealand white rabbits subjected to 40 minutes of myocardial ischemia, followed by 3 hours of reperfusion were assigned to the following groups: ischemia and reperfusion (I/R), isoflurane (1 minimal alveolar concentration) postconditioning, and isoflurane postconditioning with hyperglycemia (15% dextrose in water infusion). ⋯ This was also blocked by hyperglycemia. Our results suggest that hyperglycemia inhibits cardioprotection provided by isoflurane postconditioning. This effect seems to be mediated via modulation Akt and eNOS.
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J. Cardiovasc. Pharmacol. · Apr 2010
Randomized Controlled Trial Comparative StudyComparative study of nifekalant versus amiodarone for shock-resistant ventricular fibrillation in out-of-hospital cardiopulmonary arrest patients.
In Japan, intravenous nifekalant (NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for resuscitation. ⋯ AMD may be borderline superior over NIF to facilitate defibrillation in out-of-hospital patients with cardiopulmonary arrest. However, from the view point of preservation of brain function, NIF is not inferior to AMD for CPR.
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J. Cardiovasc. Pharmacol. · Mar 2010
Intrapericardial ranolazine prolongs atrial refractory period and markedly reduces atrial fibrillation inducibility in the intact porcine heart.
Extensive experimental studies and clinical evidence (Metabolic Efficiency with Ranzolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction-36 [MERLIN TIMI-36] trial) indicate potential antiarrhythmic efficacy of the antianginal agent ranolazine. Delivery of agents into the pericardial space allows high local concentrations to be maintained in close proximity to myocardial tissue while systemic effects are minimized. ⋯ IPC ranolazine exhibits striking atrial antiarrhythmic actions as evidenced by increases in refractoriness and in fibrillation inducibility without significantly altering mean arterial blood pressure. Ranolazine's effects on the atria appear to be more potent than those on the ventricles.