CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SIMULATION STUDY OF THE EFFECTS OF ACIDOSIS ON CARDIOMYOCYTES. MODEL ABILITY TO PRODUCE SPONTANEOUS DEPOLARIZATION
Autor/es:
NEGRONI JA,; LASCANO EC; SAID M; MUNDIÑA-WEILENMANN C.; VITTONE L,; . VALVERDE CA*, MUNDIÑA-WEILENMANN C*, SAID M, FERRERO P, VITTONE L, SALAS M, PALOMEQUE J, VILA PETROFF M, MATTIAZZI A.
Lugar:
Ciudad Autónoma de Buenos Aires - Buenos Aires - Argentina
Reunión:
Congreso; XVII Meeting of ISHR Latin American Section; 2009
Institución organizadora:
ISHR sección Latinoamericana
Resumen:
Acidosis in cardiac myocytes is a major factor in reducing filament responsiveness and contractility and the return from acidosis is associated with arrhythmia generation. The aim of this work was to build a mathematical model that represents the effects on  cardiomyocytes of decreasing pH and explore its ability to produce spontaneous postacidotic depolarizations. Methods: The 10 Tusscher–Panfilov (TP) human  entricular myocyte model with the contractile mechanism developed by Negroni–Lascano was used, adding the Na+-H+ exchanger, the effect of pH on different flows from the Crampin model and representing Ca2+ leak as part of the ryanodine receptor (RyR) conductance. The leak from the sarcoplasmic reticulum (SR) towards the cleft postulated by Shannon was adopted, assuming a closed state which allows Ca2+ flow with a maximal conductance from the TP model for leak flow. Results: Six minutes of acidosis (pH=6.7) increased Ca2+ transient, intracellular Na+, and SR Ca2+ content, decreasing isometric force and APD90. The model reproduced the spontaneous depolarizations that appear upon the return to normal pH (7.15) persisting for 2 min in the immediate post acidotic period. Conclusion: Incorporation of the SR leak in the representation of the RyR mechanism allows the reproduction of experimentally reported post-acidosis spontaneous depolarizations
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