Abstract：
PURPOSE:Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na (+) current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazine modifies the electrophysiological responses induced by acute mechanical stretch. METHODS:The ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (n = 9) or during perfusion of the late Na(+) current blocker ranolazine 5 μM (n = 9). Spectral and mapping techniques were used to establish the ventricular fibrillation dominant frequency, the spectral concentration and the complexity of myocardial activation in three situations: baseline, stretch and post-stretch. RESULTS:Ranolazine attenuated the increase in ventricular fibrillation dominant frequency produced by stretch (23.0 vs 40.4 %) (control: baseline =13.6 ± 2.6 Hz, stretch = 19.1 ± 3.1 Hz, p < 0.0001; ranolazine: baseline = 1.4 ± 1.8 Hz, stretch =14.0 ± 2.4 Hz, p < 0.05 vs baseline, p < 0.001 vs control). During stretch, ventricular fibrillation was less complex in the ranolazine than in the control series, as evaluated by the lesser percentage of complex maps and the greater spectral concentration of ventricular fibrillation. These changes were associated to an increase in the fifth percentile of VV intervals during ventricular fibrillation (50 ± 8 vs 38 ± 5 ms, p < .01) and in the wavelength of the activation (2.4 ± 0.3 vs 1.9 ± 0.2 cm, p < 0.001) under ranolazine. CONCLUSIONS:The late inward Na(+) current inhibitor ranolazine attenuates the electrophysiological effects responsible for the acceleration and increase in complexity of ventricular fibrillation produced by myocardial stretch.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Chorro FJ,del Canto I,Brines L,Such-Miquel L,Calvo C,Soler C,Parra G,Zarzoso M,Trapero I,Tormos Á,Alberola A,Such Ldoi
10.1007/s10557-015-6587-4subject
Has Abstractpub_date
2015-06-01 00:00:00pages
231-41issue
3eissn
0920-3206issn
1573-7241journal_volume
29pub_type
杂志文章abstract：:Cardiac reperfusion injury after heart transplantation or cardiopulmonary bypass has been difficult to control due to the variable degree of myocardial damage with respect to the length of ischemia and the complexity of the surgical procedure. Here, we evaluated the myocardial metabolic and functional recovery of hear...
journal_title：Cardiovascular drugs and therapy
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journal_title：Cardiovascular drugs and therapy
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