caa a22 4500 477112706 CHVBK 20180405111614.0 cr unu---uuuuu 170330e19961101xx s 000 0 eng 10.1007/BF01747188 doi (NATIONALLICENCE)springer-10.1007/BF01747188 Effects of pinacidil, verapamil, and heart rate on afterdepolarizations in the guinea-pig heart in vivo [Elektronische Daten] [Jiang Xu, Sina Zaim, Amir Pelleg] Summary: Recently, ionic current simulation in the Luo-Rudy model has elucidated putative mechanisms of afterdepolarizations under various experimental conditions. The present study was aimed at gaining insight into the differential mechanism of different types of afterdepolarizations in the guinea-pig heart in vivo. The effects of pharmacological and heart rate perturbations on early (EADs) and delayed (DADs) afterdepolarizations, induced by either digoxin, CsCl, or BayK 8644 were studied, using mid-myocardial left ventricular monophasic action potential (MAP) recordings. Digoxin insignificantly shortened sinus cycle length (SCL) and CsCl and BayK 8644 differentially prolonged SCL and MAP duration. Digoxin induced phase 3-EADs and DADs and CsCl or BayK 8644 induced phase 2- and phase 3-EADs. Pinacidil shortened MAP duration, suppressed almost all the phase 2-EADs and some of the phase 3-EADs, but not the DADs. In a few cases, DADs were manifested following the abolishment of phase 2-EADs by pinacidil, but this phenomenon did not occur in the presence of hexamethonium. Verapamil prolonged SCL, did not significantly affect phase 2-EADs, but suppressed almost all of the DADs, including those which appeared after pinacidil, and all but one of the phase 3-EADs. The effects of pinacidil and verapamil were independent of the mode of afterdepolarization induction. A pacing-induced heart rate increase, which shortened MAP duration, and vagal stimulation, which prolonged MAP duration, attenuated and enhanced phase 2-EADs, respectively. The amplitude of phase 3-EADs was inversely related to the heart rate. These data, taken together, are consistent with those obtained previously by others in a computer model and recent observations on CsCl-induced EADs in the guinea-pig Purkinje fibers in vitro which have indicated that the mechanism of phase 2-EADs is different from that of DADs and that late phase 3-EADs generated under conditions of Ca2+ overload and DADs share similar properties. Springer-Verlag, 1996 EAD nationallicence DAD nationallicence Ionic currents nationallicence Arrhythmias nationallicence Triggered activity nationallicence Xu Jiang Likoff Cardiovascular Institute, Allegheny University of Health Sciences Department of Medicine, 19102, Philadelphia, PA, USA aut Zaim Sina SUNY, Health Sciences Center, 11794, Stony Brook, NY, USA aut Pelleg Amir Likoff Cardiovascular Institute, Allegheny University of Health Sciences Department of Medicine, 19102, Philadelphia, PA, USA aut Heart and Vessels Springer-Verlag 11/6(1996-11-01), 289-302 0910-8327 11:6<289 1996 11 380 https://doi.org/10.1007/BF01747188 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01747188 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Xu Jiang Likoff Cardiovascular Institute, Allegheny University of Health Sciences Department of Medicine, 19102, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Zaim Sina SUNY, Health Sciences Center, 11794, Stony Brook, NY, USA aut NATIONALLICENCE 700 1- Pelleg Amir Likoff Cardiovascular Institute, Allegheny University of Health Sciences Department of Medicine, 19102, Philadelphia, PA, USA aut NATIONALLICENCE 773 0- Heart and Vessels Springer-Verlag 11/6(1996-11-01), 289-302 0910-8327 11:6<289 1996 11 380 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer