© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Ionic basis of ventricular arrhythmias in remodeled rat heart during long-term myocardial infarction
aUnité de Recherches INSERM U-390, Physiopathologie Cardiovasculaire, IFR N°3 Communications Cellulaires Normales et Pathologiques, CHU Arnaud de Villeneuve, F-34295 Montpelier, France
bLaboratorio de Electrofisiologia, Instituto de Cardiologia y Cirugia Cardiovascular, La Habana, Cuba
vassort{at}u390.montp.inserm.fr
* Corresponding author. Tel.: +33-04-6741-5240; fax: +33-04-6741-5242
Objective: Deleterious electrical abnormalities evolve during myocardial infarction. The goal of this study was to analyse current changes during the late decompensated phase of heart disease induced by coronary ligation and to compare them in various heart regions. Methods: Young rats were submitted to left coronary ligature. After 4–6 months, cells were enzymatically dissociated and isolated from the upper part basal region of the left ventricle, as well as from the septum, apex and the right ventricle before being studied under whole-cell patch-clamp. Results: Basal L-type Ca2+ current, ICaL elicited at +10 mV did not exhibit regional dependence neither in control nor after post-myocardial infarction (PMI). ICaL showed both a significantly reduced peak amplitude (17.1±2.8 pA/pF versus 9.9±1.4 pA/pF in seven control and seven PMI hearts, n=32 and 40, respectively) and a slower inactivation, such that the amount of inward charges during a 200 ms-depolarizing pulse was nearly unchanged. β-Adrenergic stimulation was less effective in increasing ICaL in PMI cells but it slowed inactivation further. Significant differences in the K+ currents were observed. A regional distribution was seen for Ito only, with the largest amplitude in the right ventricle (in pA/pF: 23.1±2.4, 18.2±3.9, 14.8±2.4, 8.3±1.7 in the right ventricle, apex, septum and left ventricle, respectively n=8, 7, 8 and 9). This was also true in failing heart cells despite Ito being halved in each of the four regions (in pA/pF: 12.2±2.5, 11.2±1.9, 5.1±1.0 and 4.8±1.0, respectively n=12, 12, 11 and 13). IK1 was also significantly reduced by 20% in the PMI cells. Two-way analyses of variance demonstrated the absence of interaction between the topographical origin of the cells and the physiological state of the rats. The 
1-adrenergic agonist, methoxamine significantly reduced Ito and IK1 to the same extent in both sham and PMI cells, by about 35% and 20% respectively. Conclusions: Long-term left coronary occlusion induces significant alterations in both Ca2+ and K+ currents that occur with similar amplitude in both ventricles. They include a marked reduction in Ito amplitude as well as a slowing of ICaL inactivation. Both factors could contribute to the disturbances in cellular electrical behaviour and the occurrence of arrhythmias in the post-myocardial infarcted heart.
KEYWORDS Cm, membrane capacitance; PMI, post-myocardial infarction; APD, action potential duration; ICaT, T-type Ca2+ current; ICaL, L-type Ca2+ current; Ito, transient outward K+ current; IK, delayed outward K+ current; IK1, inward rectifying K+ current; I/V, current/voltage
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