Effects of acute global low-flow ischemia on triggered arrhythmias in d-sotalol-induced long Q-T intervals in perfused rabbit hearts.
Little information is available on how acute ischemia modifies the electrophysiologic substrate associated with long Q-T interval conditions. We studied the effects of low-flow ischemia (10 min at 5.0 ml/min followed by 10 min of 2.5 ml/min) in Langendorff perfused rabbit hearts during control and in hearts 20 min after the addition to the perfusate of 92 microM d-sotalol, which reliably produced triggered activity. Epicardial electrograms, a left ventricular endocardial monophasic action potential (MAP), and simulated X and Y lead electrocardiograms were used to characterize myocardial activation and recovery during ventricular pacing. In the control hearts, conduction velocity as indicated by the mean epicardial activation time accelerated for most of the period of ischemia (maximum decrease of -9.4 +/- 7.9%). The mean activation-recovery interval, MAP duration, and Q-T interval were moderately decreased (-4.9 +/- 8.6%, -7.5 +/- 4.4%, and -4.6 +/- 2.3%, respectively). The mean standard deviation of the activation-recovery interval (epicardial heterogeneity of recovery) was increased by 34.6 +/- 23.4%. d-Sotalol had no effect on conduction but prolonged myocardial recovery time, increased heterogeneity, and produced triggered arrhythmias in all hearts. Within 2 min of ischemia triggered activity was eliminated. With d-sotalol, ischemia slowed conduction and produced relatively larger decreases in the activation-recovery interval, MAP duration, and Q-T interval (-11.8 +/- 10.3%, -13.9 +/- 12.0%, and -15.8 +/- 11.2%). The increased epicardial heterogeneity seen with d-sotalol was attenuated by ischemia. Thus ischemia superimposed on long Q-T conditions had antiarrhythmic as well as arrhythmogenic effects.
Spear
J F
JF
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6046, USA.
Moore
E N
EN
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010477:Perfusion; D011188:Potassium / Q000502:physiology; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013015:Sotalol / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D013015:Sotalol; D011188:Potassium