TY  - JOUR
AB  - The aim of this study was to investigate the effects of a combination of ranolazine with different selective inhibitors of the Na+/Ca2+-exchanger (NCX) in an established experimental model of atrial fibrillation (AF). Eighteen hearts of New Zealand white rabbits were retrogradely perfused. Atrial catheters were used to record monophasic action potentials (aPRR). Hearts were paced at three different cycle lengths. Thereby, atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness were obtained. Isoproterenol and acetylcholine were employed to increase the occurrence of AF. Thereafter, the hearts were assigned to two groups (n = 9 each group) and additionally perfused with a combination of 10 µM ranolazine and 1 µM of the selective NCX-inhibitor ORM-10103 (group A: Rano-ORM) or 10 µM ranolazine and 1 µM of another NCX-inhibitor, SEA0400 (group B: Rano-SEA). The infusion of Iso/ACh led to a shortening of aAPD90, aERP, aPRR and the occurrence of AF episodes was significantly increased. Additional perfusion with ranolazine and ORM-10103 (group A) significantly prolonged the refractory periods and aPRR and AF episodes were effectively reduced. In group B, Rano-SEA led to a slight decrease in aAPD90 while aERP and aPRR were prolonged. The occurrence of AF episodes was consecutively reduced. To our knowledge, this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Both combinations prolonged aERP and aPRR and thereby suppressed the induction of AF.
AU  - Wolfes, Julian
AU  - Ellermann, Christian
AU  - Broer, Niklas
AU  - Rath, Benjamin
AU  - Willy, Kevin Kurt
AU  - Leitz, Patrick R.
AU  - Lange, Philipp Sebastian
AU  - Eckardt, Lars
AU  - Frommeyer, Gerrit
DA  - 2020-10-20
DO  - 10.17879/34019476370
KW  - ranolazine
KW  - NCX-inhibition
KW  - atrial fibrillation
KW  - Langendorff
LA  - eng
N1  - Pharmaceuticals 13 (2020) 10, 321, 1-9
N1  - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2020-10-20
TI  - Antiarrhythmic Effect of Ranolazine in Combination with Selective NCX-Inhibition in an Experimental Model of Atrial Fibrillation
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-73099699529
Y2  - 2024-11-22T06:01:47
ER  -