학술논문
Dispersion of cell-to-cell uncoupling precedes low K+-induced ventricular fibrillation
Document Type
TEXT
Author
Source
Subject
Language
English
Multiple Languages
Multiple Languages
Abstract
N. Tribulová, M. Manoach, D. Varon, L. Okruhlicová, T. Zinman , A. Shainberg.
Obsahuje bibliografii
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.
Obsahuje bibliografii
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.