Search

–Left ventricular hypertrophy (LVH) is frequently associated with clinical atrial arrhythmias, but little is known about how it causes those arrhythmias. Our previous studies have shown that LVH increases the late sodium current (1N Na L) that plays an important role in the genesis of ventricular arrhythmias. We hypothesize that LVH may also induce an upregulation of the 1 N Na L in atrial myocytes, leading to atrial electrical abnormalities. The renovascular hypertension model was used to induce LVH in rabbits. Action potential and membrane current recordings were performed in single myocytes. At a pacing cycle length of 2,000 ms, spontaneous phas – 2 early afterdepolarizations (EADs) could be recorded from the left atrial myocytes in 10 of 12 LVH rabbits, whereas no EADs could be elicited in right atrial myocytes of LVH rabbits or atrial myocytes from any of the 12 control rabbits. Spontaneous automaticity (SA) from left atrial myocytes was observed in 9 out of 12 LVH rabbits, but none in right atrial myocytes of LVH rabbits or control rabbits, at a pacing rate of 8,000 ms. The left atrial myocytes of LVH rabbits had a significantly higher density of the 1 Na – L compared with those of control rabbits (0.90 ± 0.12 in LVH vs. 0.50 ± 0.08 pA/pF in control, n = 8, P < 0.01). Tetrodotoxin, an 1 Na – L blocker, abolished all atrial EADs and SA at 10 μM. Our results demonstrate that LVH induction results in a significant increase of 1 Na – L in the left atrial myocytes that may render these cells susceptible to the genesis of EADs and SA. The 1 Na– L may serve as a potentially useful ionic target for antiarrhythmic drugs for the treatment of atrial arrhythmias in the setting of LVH. [ABSTRACT FROM AUTHOR]

T-wave alternans, characterized by a beat-to-beat change in T-wave morphology, amplitude, and/or polarity on the ECG, often heralds the development of lethal ventricular arrhythmias in patients with left ventricular hypertrophy (LVH). The aim of our study was to examine the ionic basis for a beat-to-beat change in ventricular repolarization in the setting of LVH. Transmembrane action potentials (APs) from epicardium and endocardium were recorded simultaneously, together with transmural ECG and contraction force, in arterially perfused rabbit left ventricular wedge preparation. APs and Ca2+-activated chloride current (ICl,Co) were recorded from left ventricular myocytes isolated from normal rabbits and those with renovascular LVH using the standard microelectrode and whole cell patch-clamping techniques, respectively. In the LVH rabbits, a significant beat-to-beat change in endocardial AP duration (APD) created beat-to-beat alteration in transmural voltage gradient that manifested as T-wave alternans on the ECG. Interestingly, contraction force alternated in an opposite phase ("out of phase") with APD, In the single myocytes of LVH rabbits, a significant beat-to-beat change in APD was also observed in both left ventricular endocardial and epicardial myocytes at various pacing rates. APD alternans was suppressed by adding 1 µM ryanodine, 100 µM 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), and 100 µM 4-acetamido-4′-isothiocyanostilbene-2,2′-disulfonic acid (SITS). The density of the Ca2+-activated chloride currents (ICl,Ca) in left ventricular myocytes was significantly greater in the LVH rabbits than in the normal group. Our data indicate that abnormal intracellular Ca2+ fluctuation may exert a strong feedback on the membrane ICl,Ca, leading to a beat-to-beat change in the net repolarizing current that manifests as T-wave alternans on the ECG. [ABSTRACT FROM AUTHOR]