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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

A prospective comparison of class IA, B, and C antiarrhythmic agents in combination with amiodarone in patients with inducible, sustained ventricular tachycardia.

BACKGROUND. Clinical experience suggests that combinations of antiarrhythmic agents provide more effective control of ventricular tachyarrhythmias than does therapy with single agents. METHODS AND RESULTS. Antiarrhythmic and electrophysiological effects of three class I antiarrhythmic agents, one from each subclass A, B, and C, were assessed in single use and in combination with amiodarone in patients with inducible, sustained ventricular tachycardia that was not suppressed by monotherapy with these agents. Thirty-one patients underwent an electrophysiology test on four occasions: at baseline; after 2-4 days of treatment with quinidine, mexiletine, or encainide; after 2 weeks of treatment with 1,200 mg/day amiodarone; and last, after 2-4 days of treatment with both amiodarone and the previously tested class I agent. The combination of a class I agent and amiodarone prevented the induction of sustained ventricular tachycardia in only one of 31 (3%) patients. Ventricular tachycardia became hemodynamically stable in 11 of 31 (34%) patients because of a marked prolongation in the tachycardia cycle length. It increased from 323 +/- 39 to 423 +/- 84 msec (n = 11, p less than 0.01) by adding encainide to amiodarone therapy, and it showed a tendency to lengthen when quinidine was added to amiodarone (from 373 +/- 77 to 425 +/- 58 msec; n = 10, NS). Each class I agent increased amiodarone-induced depression in myocardial conduction, but the extent of the additional depression seemed to differ among the three subclasses. Ventricular refractoriness was increased by all class I agents when used in combination with amiodarone, although not by mexiletine or encainide when used alone. CONCLUSIONS. Class I antiarrhythmic agents slow ventricular conduction and increase ventricular refractoriness when used in combination with amiodarone. When amiodarone and class I drugs by themselves do not suppress the induction of ventricular tachycardia, the combination of amiodarone and a class I agent seldom results in noninducibility; however, it often lengthens the ventricular tachycardia cycle length and may render the ventricular tachycardia hemodynamically stable.[1]


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