title: Coronary occlusion and reperfusion promote early afterdepolarizations and ventricular tachycardia in a canine tissue model of type 3 long QT syndrome.
abstract: Although long QT syndrome (LQTS) and coronary occlusion-reperfusion (O/R) are arrhythmogenic, they affect ventricular action potential duration (APD) differently. In contrast to the prolonged APD in LQTS, ischemia abbreviates APD after a transient prolongation. Thus we hypothesized that the dynamic interactive effects of ischemia and LQTS on APD and its dispersion would affect ventricular arrhythmogenicity. We mapped transmural distribution of action potentials in 6 groups of 10 isolated wedges of canine ventricular walls: LQTS-O/R, LQTS only, and O/R only, with separate groups for pacing cycle lengths (PCL) of 1,000 and 2,000 ms. We created type 3 LQTS with anemone toxin (ATX) II followed >30 min later by arterial occlusion (40 min) and reperfusion (>100 min). Arterial occlusion initially (first 4 min) prolonged and then shortened APD. Early afterdepolarizations (EADs) occurred during the initial 4 min of occlusion in 4 of the 10 LQTS-O/R wedges at PCL of 2,000 ms but not in the other groups. Reperfusion restored APD in the O/R-only groups but caused APD to overshoot its original duration, indicating depressed repolarization reserve, in the LQTS-O/R group. Reperfusion increased the dispersion of APDs and initiated ventricular tachycardia-fibrillation in 7 of 10 and 6 of 10 LQTS-O/R wedges and in 2 of 10 and 1 of 10 O/R-only wedges at PCLs of 1,000 and 2,000 ms, respectively. The LQTS-only wedges exhibited neither EADs nor ventricular tachycardia. We conclude that coronary O/R increased the arrhythmogenicity of LQTS via cumulative prolongation of APD, increase in repolarization dispersion, and suppression of repolarization reserve.
authors.affiliation: Krannert Institute of Cardiology, Indiana Univ. School of Medicine, 1800 North Capitol Ave., Indianapolis, IN 46202, USA.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ueda
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Zipes
authors.forename: Jiashin
authors.initials: J
authors.lastname: Wu
mesh_terms: D000200:Action Potentials; D000818:Animals; D003064:Cnidarian Venoms; D003327:Coronary Disease / Q000150:complications*; D004195:Disease Models, Animal; D004285:Dogs; D066298:In Vitro Techniques; D008133:Long QT Syndrome / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D011930:Reaction Time; D017180:Tachycardia, Ventricular / Q000209:etiology*
chemical_list: D003064:Cnidarian Venoms; C028800:toxin II (Anemonia sulcata)