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

Rapid rates during bradycardia prolong ventricular refractoriness and facilitate ventricular tachycardia induction with cesium in dogs.

BACKGROUND: Bradycardia can promote the development of some ventricular techycardias (VTs). We investigated whether relative bradycardia per se or the transition from a rapid to a slower ventricular rate might be important in developing VT. METHODS AND RESULTS: We studied groups of anesthetized closed-chest dogs that had AV produced by radiofrequency catheter ablation of the AV junction. One group had uninterrupted AV block; the other group underwent a period of rapid left ventricular pacing. Both groups then received incremental doses of CsCl until sustained VT resulted. We also measured ventricular effective refractory period (V-ERP) and QT interval in separate groups of dogs that had AV block for 1 week or 3 days with and without rapid pacing (pacing cycle length [PCL] = 500 or 250 ms) for 1 hour or 30 minutes. Finally, we investigated the effects of rapid pacing on V-ERP by testing the effects of verapamil and autonomic denervation on these changes. We found that CsCl induced larger early afterdepolarizations and a greater prevalence of VT in dogs with rapid pacing than in dogs without. In dogs that had AV block for 1 week, 1 hour of rapid pacing prolonged V-ERP and QT interval compared with V-ERP and QT interval before pacing. Changes persisted for at least 3 hours. Rapid pacing for only 30 minutes and at a PCL of 250 ms, as well as superimposition on sinus rhythm, each prolonged V-ERP but to a lesser extent. Only 3 days of complete AV block and autonomic denervation did not affect the prolongation of V-ERP produced by rapid pacing, whereas verapamil significantly blunted but did not eliminate the prolongation. CONCLUSIONS: At the same PCLs, the heart exposed to transient tachycardia superimposed on bradycardia exhibited a longer V-ERP, QT interval, and monophasic action potential duration and greater ease for developing VT than the heart exposed only to bradycardia. The prolongation of refractoriness lasted for at least 3 hours, and the delta-ERP was influenced by the heart rate before pacing, the duration of pacing, and the PCL. The mechanism for this response to rapid rates appears to involve calcium, at least in part.[1]


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