Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF (n = 18) and control (n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17–81%), and conduction velocity was significantly decreased in CHF (by 6–20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.
Proline-rich tyrosine kinase 2 (Pyk2) is a nonreceptor protein kinase regulated by intracellular Ca2+, CaMK, and PKC and can be activated by different stress signals involved in heart failure. However, Pyk2 has not been investigated in the human heart, and the functional role of Pyk2 signaling at...
Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate-dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further ...
High-Rate Pacing Prevents Drug-Induced Arrhythmias. High-rate pacing may have an inhibitory effect on the initiation of Torsade de Pointes arrhythmias (TdP). However, permanent pacing is only indicated in high-risk patients. We performed a proof of concept study into automatic overdrive pacing fo...
The purpose of this study was to investigate the effect of stretch (the major risk factor for atrial fibrillation [AF]) on spatial and temporal alternations of action potential duration (APD-ALT) and calcium transient in cultured atrial myocyte monolayer.How rapid firings or premature beats trigg...
Transgenic rabbits expressing loss-of-function pore mutants of the human gene KCNQ1 (KvLQT1-Y315S) have a Long QT-Syndrome 1 (LQT1) phenotype. We evaluated for the first time the effect of nicorandil, an opener of ATP-sensitive potassium channels, and of isoproterenol on cardiac action potential ...
Clinical observations in patients with long QT syndrome carrying sodium channel mutations (LQT3) suggest that bradycardia caused by parasympathetic stimulation may provoke torsades de pointes (TdP). β-Adrenoceptor blockers appear less effective in LQT3 than in other forms of the disease.Meth...
Present study examined the role of the late sodium current (INa,L) in normal rate-dependence of ventricular repolarization and reverse use-dependence of QT prolonging agents. Methods and The effects of INa,L blockade, INa,L enhancement, IKr blockade and changes in extracellular potassium conce...
The presence of M3 cholinoreceptors and their role in mediation of action potential waveform modulation were determined by immunolabeling of receptor proteins and standard microelectrode technique, respectively. The sinoatrial node (SAN), which was determined as a connexin 43 negative area within...
submitted by alegonzalezk 2 years and 5 months ago
The reduced heart rate and prolonged QTend duration in mice deficient in thyroid hormone receptor (TR) [alpha]1 may involve aberrant expression of the K+ channel [alpha]-subunit KCNQ1 and its regulatory beta-subunit KCNEHere we focus on KCNE1 and study whether increased KCNE1 expression can expla...
