Ionic basis of ventricular arrhythmias in remodeled rat heart during long-term myocardial infarction

Objective: Deleterious electrical abnormalities evolve during myocardial in farction. 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 submitte d to left coronary ligature. After 4-6 months, cells were enzymatically dis sociated and isolated from the upper part basal region of the left ventricl e, as well as from the septum, apex and the right ventricle before being st udied under whole-cell patch-clamp. Results: Basal L-type Ca2+ current, I-C aL elicited at +10 mV did not exhibit regional dependence neither in contro l nor after post-myocardial infarction (PMI). I-CaL showed both a significa ntly reduced peak amplitude (17.1+/-2.8 pA/pF versus 9.9+/-1.4 pA/pF in sev en control and seven PMI hearts, n=32 and 40, respectively) and a slower in activation, such that the amount of inward charges during a 700 ms-depolari zing pulse was nearly unchanged. beta-Adrenergic stimulation was less effec tive in increasing I-CaL in PMI cells but it slowed inactivation further. S ignificant differences in the K+ currents were observed. A regional distrib ution was seen for I-to only, with the largest amplitude in the right ventr icle (in pA/pF: 23.1+/-2.4, 18.3+/-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 I-to 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). I-KI was also significantly reduce d by 20% in the PMI cells. Two-way analyses of variance demonstrated the ab sence of interaction between the topographical origin of the tells and the physiological state of the rats. The alpha(1)-adrenergic agonist, methoxami ne significantly reduced I-to and I-KI to the same extent in both sham and PMI cells, by about 35% and 20% respectively. Conclusions: Long-term left c oronary occlusion induces significant alterations in both Ca2+ and K+ curre nts that occur with similar amplitude in both ventricles. They include a ma rked reduction in I-to amplitude as well as a slowing of I-CaL inactivation . Both factors could contribute to the disturbances in cellular electrical behaviour and the occurrence of arrhythmias in the post-myocardial infarcte d heart. (C) 1999 Elsevier Science B.V. All rights reserved.