Electrophysiological determinants of hypokalaemia-induced arrhythmogenicity in the guinea-pig heart.
OBJECTIVE
Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia-induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea-pig heart preparations.


METHODS
Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume-conducted electrocardiogram (ECG) during steady-state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions.


RESULTS
Hypokalaemic perfusion (2.5 mm K(+) for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re-excitation. Hypokalaemia increased the RV-to-LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD(90) and refractoriness across the LV wall. As determined by local activation time recordings, the LV-to-RV transepicardial conduction and the LV transmural (epicardial-to-endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds.


CONCLUSIONS
These findings suggest that hypokalaemia-induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re-excitation, amplified RV-to-LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea-pig heart.
Osadchii
O E
OE
Department of Biomedical Sciences, The Danish National Research Foundation Centre for Cardiac Arrhythmia, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark. osadchii@mail.ru
Olesen
S P
SP
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D006329:Heart Conduction System / Q000502:physiology / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D007008:Hypokalemia / Q000150:complications*; D009200:Myocardial Contraction / Q000502:physiology