کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2922121 | 1175835 | 2013 | 8 صفحه PDF | دانلود رایگان |
BackgroundBrugada syndrome is an inherited disease associated with vulnerability to ventricular tachycardia and sudden cardiac death in young adults. Milrinone and cilostazol, oral phosphodiesterase (PDE) type III inhibitors, have been shown to increase L-type calcium channel current (ICa) and modestly increase heart rate by elevating the level of intracellular cyclic adenosine monophosphate.ObjectiveTo examine the effectiveness of these PDE inhibitors to suppress arrhythmogenesis in an experimental model of Brugada syndrome.MethodsAction potential (AP) and electrocardiographic recordings were obtained from epicardial and endocardial sites of coronary-perfused canine right ventricular wedge preparations. The Ito agonist NS5806 (5 μM) and Ca2+ channel blocker verapamil (2 μM) were used to pharmacologically mimic Brugada phenotype.ResultsThe combination induced all-or-none repolarization at some epicardial sites but not others, leading to ST-segment elevation as well as an increase in both epicardial and transmural dispersion of repolarization. Under these conditions, phase 2 reentry developed as the epicardial AP dome propagated from sites where it was maintained to sites at which it was lost, generating closely coupled extrasystoles and ventricular tachycardia. The addition of the PDE inhibitor milrinone (2.5 μM) or cilostazol (5–10 μM) to the coronary perfusate restored the epicardial AP dome, reduced dispersion, and abolished phase 2 reentry-induced extrasystoles and ventricular tachycardia.ConclusionsOur study identifies milrinone as a more potent alternative to cilostazol for reversing the repolarization defects responsible for the electrocardiographic and arrhythmic manifestations of Brugada syndrome. Both drugs normalize ST-segment elevation and suppress arrhythmogenesis in experimental models of Brugada syndrome.
Journal: Heart Rhythm - Volume 10, Issue 11, November 2013, Pages 1720–1727