Dispersion of cell-to-cell uncoupling precedes low K+-induced ventricular fibrillation

Title:

Dispersion of cell-to-cell uncoupling precedes low K+-induced ventricular fibrillation

Creator:

Narcisa Tribulová, Manoach, M., Varon, D., Ľudmila Okruhlicová, Zinman, T., and Shainberg, A.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:7f02b904-48d6-4bff-b1cd-2088637b9fe8
uuid:7f02b904-48d6-4bff-b1cd-2088637b9fe8
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, fyziologie, physiology, hypokalemia, ventricular fibrillation, connexin-43, intercellular junction, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

a1_We hypothesize that hypokalemia-related electrolyte imbalance linked with abnormal elevation of intracellular free Ca2+ concentration can cause metabolic disturbances and subcellular alterations resulting in intercellular uncoupling, which favor the occurrence of malignant arrhythmias. Langendorff-perfused guinea pig heart (n = 44) was subjected to a standard Tyrode solution (2.8 mmol/l K+) followed by a K+-deficient solution (1.4 mmol/l K+). Bipolar ECG of the left atria and ventricle was continuously monitored and the incidence of ventricular fibrillation was evaluated. Myocardial tissue sampling was performed during stabilization, hypokalemia and at the onset of fibrillation. Enzyme activities of succinic dehydrogenase, glycogen phosphorylase and 5-nucleotidase were determined using in situ catalytic histochemistry. The main gap junction protein, connexin-43, was labeled using mouse monoclonal antibody and FITC conjugated goat antimouse antibody. Ultrastructure was examined by transmission electron microscopy. The free Ca2+ concentration was measured by the indo-1 method in ventricular cell cultures exposed to a K+-free medium. The results showed that sustained ventricular fibrillation appeared within 15-30 min of low K+ perfusion. This was preceded by ectopic activity, episodes of bigeminy and tachycardia. Hypokalemia induced moderate reversible and sporadically irreversible subcellular alterations of cardiomyocytes and impairment of intercellular junctions, which were heterogeneously distributed throughout myocardium. Patchy areas with decreased enzyme activities and diminished immunoreactivity of connexin-43 were found. Furthermore, lack of external K+ was accompanied by an increase of intracellular Ca2+. The prevention of Ca2+ overload by either 1 mmol/l Ni2+ (Na+/Ca2+ inhibitor), 2.5 mmol/l verapamil, 10 mmol/l d-sotalol or 10 mmol/l tedisamil was associated with the protection agains fibrillation., a2_The results indicate that hypokalemia induces Ca2+ overload injury and disturbances in intercellular coupling. Dispersion of these changes throughout the myocardium may serve as the basis for microreentry circuits and thus favor fibrillation occurrence., N. Tribulová, M. Manoach, D. Varon, L. Okruhlicová, T. Zinman , A. Shainberg., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2001 Volume:50 | Number:3

Harvested from:

CDK

Metadata only:

false