Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Sep 2008
Glycogen synthase kinase 3 inhibition protects the heart from acute ischemia-reperfusion injury via inhibition of inflammation and apoptosis.
Glycogen synthase kinase (GSK)-3beta inhibitors play an anti-inflammatory role in several inflammatory diseases. Recent studies have demonstrated that GSK-3beta inhibitors protect against myocardial ischemia-reperfusion injury. However, the precise mechanisms remain unclear. ⋯ Administration of TDZD-8 significantly suppressed nuclear factor kappa B (NF-kappaB) and p38 MAPK activation (P < 0.05 vs. myocardial ischemia-reperfusion) and the concentrations of the myocardial-derived cytokines tumor necrosis factor-alpha (TNF-alpha, 107.40 +/- 7.34 pg/mg protein vs. myocardial ischemia-reperfusion group, P < 0.05) and interleukin-6 (IL-6, 29.28 +/- 6.3 pg/mg protein vs. myocardial ischemia-reperfusion group, P < 0.05). Treatment with TDZD-8 also inhibited myocardial cell apoptosis compared with the myocardial ischemia-reperfusion group (12 +/- 1% vs. 22 +/- 2%, P < 0.05). Therefore, blocking this protein kinase activity may be a novel approach to the treatment of this condition, which is characterized by inflammation and apoptosis.
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J. Cardiovasc. Pharmacol. · Jul 2008
ReviewWill warfarin soon be passé? New approaches to stroke prevention in atrial fibrillation.
Atrial fibrillation (AF) is the most common cause for thromboembolic stroke. Oral anticoagulation with warfarin is still the most effective therapy in patients with AF, who are at an increased risk for stroke. ⋯ Furthermore, the pathophysiology of prothrombotic endocardial remodeling in fibrillating atria suggests that angiotensin II increases prothrombotic expression of vascular adhesion molecules at the atrial endocardium. Thus, novel anticoagulants or hybrid therapy with a combination of anticoagulants with inhibitors of endocardial remodelling like angiotensin II receptor blockers appear to be attractive future perspective approaches.
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J. Cardiovasc. Pharmacol. · Jul 2008
In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig.
The long QT syndrome is characterized by a prolongation of the QT interval measured on the surface electrocardiogram. Prolonging the QT interval increases the risk of dangerous ventricular fibrillations, eventually leading to sudden cardiac death. Pharmacologically induced QT interval prolongations are most often caused by antagonizing effects on the repolarizing cardiac current called IKr. ⋯ Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a hERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically induced QT prolongation in both anaesthetized and conscious guinea pigs.
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J. Cardiovasc. Pharmacol. · Apr 2008
ReviewEffects of modifying triglycerides and triglyceride-rich lipoproteins on cardiovascular outcomes.
Elevated levels of triglycerides (and triglyceride-rich lipoproteins) are increasingly being recognized as treatment targets to lower cardiovascular risk in certain patient subgroups, including individuals receiving HMG-CoA reductase inhibitors (statins). Evidence suggests that these agents reduce the risk of coronary events more markedly in patients with elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C). Further, intensive long-term statin therapy that reduces both low-density lipoprotein cholesterol (LDL-C) to <70 mg/dL and triglycerides to <150 mg/dL results in a decreased risk of cardiovascular events compared with more moderate statin treatment. ⋯ Elevated triglycerides also constitute a plausible therapeutic target in certain patients with coronary heart disease (and/or insulin resistance) but without profound LDL-C elevations. The foregoing and other evidence has led consensus panels to lower the upper limit for "normal" triglycerides to 150 mg/dL. Adequately powered randomized controlled trials that specifically assess the effects of lowering triglycerides and raising HDL-C, and trials that target individuals with high triglycerides and low HDL-C, may provide data for recommending specific treatment targets for triglycerides and HDL-C, as well as effective and well-tolerated therapies to achieve these goals.
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J. Cardiovasc. Pharmacol. · Feb 2008
Towards new indices of arterial stiffness using systolic pulse contour analysis: a theoretical point of view.
Total arterial stiffness plays a contributory role throughout aging and in numerous cardiovascular diseases, including hypertension. Aortic stiffening is responsible for an increased characteristic impedance (ie, the impedance to the left ventricular pulsatile flow), thus increasing the forward pressure-wave amplitude that contributes to pulse pressure elevation. Aortic stiffening also increases pulse wave velocity, and this results in anticipated and enhanced wave reflections, further augmenting central pulse pressure. ⋯ This allowed us to describe new time-domain estimates of characteristic impedance, pulsatile load (waveguide ratio), total arterial compliance, and total arterial stiffness. It is demonstrated that total arterial stiffness may be estimated by the following formula: [(Pi - DAP) x ST] / (SV x Deltat), where Pi is the aortic pressure at the inflection point (peak forward pressure wave), DAP is diastolic aortic pressure, ST is systolic ejection time, SV is stroke volume, and Deltat is the time-to-Pi. A mathematical relationship among time intervals and indices of pulsatile load is demonstrated, and the clinical implications are discussed in terms of cardiovascular risk and stroke volume prediction.