title: Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heart.
abstract: Diuretic-induced hypokalaemia has been shown to promote cardiac arrhythmias in hypertensive patients. The present study was designed to determine whether hypokalaemia increases arrhythmic susceptibility of the left ventricle (LV) or the right ventricle (RV), or both. Proarrhythmic effects of hypokalaemic perfusion (2.5 mm K(+) for 30 min) were assessed in isolated guinea-pig heart preparations using simultaneous recordings of volume-conducted electrocardiogram and monophasic action potentials from six ventricular epicardial sites. Effective refractory periods, ventricular fibrillation thresholds and inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing were determined at the LV and the RV epicardial stimulation sites. Hypokalaemia promoted spontaneous ventricular ectopic activity, an effect attributed to non-uniform prolongation of ventricular repolarization resulting in increased RV-to-LV transepicardial dispersion of refractoriness and action potential duration. Furthermore, hypokalaemic perfusion was associated with reduced ventricular fibrillation threshold and increased inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing as determined at the LV stimulation site. In contrast, the RV stimulation revealed no change in arrhythmic susceptibility of the RV chamber. Consistently, hypokalaemia reduced the LV effective refractory period but had no effect on the RV refractoriness. This change enabled generation of premature propagating responses by extrastimulus application at earlier time points during LV repolarization. Increased prematurity of extrastimulus-evoked propagating responses was associated with exaggerated local inhomogeneities in intraventricular conduction and action potential duration in hypokalaemic LV, thus creating a favourable stage for re-entrant tachyarrhythmias. Taken together, these findings suggest that proarrhythmic effects of hypokalaemia are mostly attributed to increased LV arrhythmogenicity in the guinea-pig heart.
authors.affiliation: The Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark. osadchii@mail.ru
authors.forename: Oleg E
authors.initials: OE
authors.lastname: Osadchii
authors.forename: Bo Hjorth
authors.initials: BH
authors.lastname: Bentzen
authors.forename: Soren Peter
authors.initials: SP
authors.lastname: Olesen
mesh_terms: D000200:Action Potentials; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate; D007008:Hypokalemia / Q000150:complications* / Q000503:physiopathology; D066298:In Vitro Techniques; D010477:Perfusion; D012032:Refractory Period, Electrophysiological; D017180:Tachycardia, Ventricular / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000503:physiopathology; D016277:Ventricular Function, Left; D016278:Ventricular Function, Right