Factors involved in the susceptibility of spontaneously hypertensive rats to low K+-induced arrhythmias.
Disorders of intracellular Ca2+ homeostasis and intercellular coupling are thought to be crucial in the initiation and maintenance of malignant arrhythmias. The aim of this study was to investigate possible arrhythmogenic factors in spontaneously hypertensive rats (SHR) as well as their susceptibility to low K+-related arrhythmias. The experiments were performed on isolated hearts of 13 weeks-old SHR and age-matched Wistar Kyoto rats (WKY). Equilibration of the heart by Langendorff perfusion with oxygenated, 37 degrees C warm, standard Krebs solution at a constant pressure was followed by perfusion with low K+ solution for 60 min, unless sustained ventricular fibrillation occurred earlier. Electrocardiogram and epicardial monophasic action potentials (MAPs) were continuously monitored for incidence of arrhythmias and action potential changes. Myocardial tissue was taken for ultrastructural analysis and immunodetection of the main gap junction protein, connexin-43. The results showed that hypertrophic hearts of SHR exhibited prolongation of MAPs and a decrease in phosphorylation of connexin-43. Moreover, they were more prone to low K+-induced early after-depolarisations and ventricular premature beats as well as to connexin-43 and ultrastructural alterations than WKY rats. Consequently, the incidence of ventricular tachycardia (70% vs. 50%) and both transient (50% vs. 25%) and sustained (60% vs. 25%) ventricular fibrillation was higher in SHR than WKY rats. The results suggest that both prolongation of MAP and connexin-43 alterations are important arrhythmogenic factors facilitating arrhythmias in the setting of Ca2+ disorders due to hypokalaemia.
Tribulova
N
N
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia. usrdtri@savba.sk
Okruhlicova
L
L
Imanaga
I
I
Hirosawa
N
N
Ogawa
K
K
Weismann
P
P
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D018031:Connexin 43 / Q000378:metabolism*; D004198:Disease Susceptibility / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate; D007008:Hypokalemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012307:Risk Factors
D018031:Connexin 43