Calcium overload plays a key role in the development of atrial electrical remodeling. The effect of an L-type Ca channel blocker in preventing this remodeling has been reported to be short lasting, partly due to down-regulation of this channel and persisting Ca entry through the T-type Ca channel. To prove if efonidipine, a dual L- and T-type Ca channel blocker exerts a greater effect than an L-type Ca channel blocker verapamil, 21 dogs underwent rapid atrial pacing at 400 bpm for 14 days, pretreatment with efonidipine in 7 (E), verapamil in 7 (V), and none in 7 (C). We measured the atrial effective refractory period (ERP) serially during 14 days of rapid pacing. In response to rapid pacing, ERP decreased progressively in C. In contrast, in E and V, ERP remained greater than ERP in C (P < 0.01) on days 2 through 7. However, on the 14th day, ERP in V decreased to the level seen in C, whereas ERP in E remained significantly longer than ERPs in C or V (P < 0.01). The blockade L-type Ca channel alone is not sufficient, but the addition of a T-type Ca channel blockade shows a more sustained effect to prevent atrial electrical remodeling.
Oral verapamil started before but not after rapid atrial excitation prevents electrical remodeling. Verapamil may exert beneficial effects when it is taken during sinus rhythm, but not after more than 2 days of atrial tachyarrhythmia.
apid atrial excitation, as seen during atrial fibrillation (AF), modifies the electrophysiological and mechanical functions of the chamber, thereby promoting the perpetuation of arrhythmias and clot formation. Even brief periods of atrial tachycardia can shorten the atrial effective refractory period (ERP), with loss of rate adaptation 1-6 and development of contractile abnormalities. 7,8 Several experimental and clinical studies have suggested that Ca overload plays a major role in the electrical and mechanical remodeling caused by prolonged rapid atrial excitation. [9][10][11][12][13] Other studies have demonstrated that AF-induced electrical and mechanical dysfunction can be reduced by pretreatment with a Ca blocker, verapamil; 14-17 however, the long-term effects of verapamil on both electrical and mechanical remodeling remain controversial. We recently reported that atrial electrical remodeling is, to at least some degree, positively correlated with mechanical remodeling in a canine rapid atrial pacing model 18 and the purpose of the present study was to demonstrate whether verapamil can prevent both electrical and mechanical atrial remodeling in a canine rapid pacing model.
Methods
Animal PreparationThe study protocol was approved by the institutional scientific review committee. For this study, we used 16 adult mongrel dogs of either sex weighing 9-15 kg (average, 12 kg). The dogs were anesthetized with an intravenous injection of pentobarbital sodium (20 mg/kg iv) and ketamine chloride (15 mg/kg iv), then intubated and placed on mechanical ventilation with a volume-cycled ventilator (Model 607 Ventilator Harvard Apparatus). The heart was exposed via a right fifth intercostal thoracotomy and suspended in a pericardial cradle with continuous surface electrocardiographic (ECG) monitoring. A custom-designed set of electrodes, comprising a pair of electrodes with a distal hook for pacing and 2 pairs of electrodes with an interelectrode distance of 15 mm aligned proximally serving for recording, was sutured to the epicardial surface of the ridge of the right atrial appendage (RAA). Each pair of electrodes was positioned with interpolar distance of 2 mm. After closure of the thorax, the distal ends of these electrode leads were tunneled subcutaneously and exposed at the back, and then connected to a pacemaker (Nihon Kohden, output of 5 V with 0.7 ms pulse duration) in the jacket. The pacemaker was programmed to provide rapid atrial pacing at 400 ppm. This rate was maintained except for a brief period for measurement of electrophysiological and mechanical parameters. Following the surgical procedure, all dogs were administered oral antibiotics during the 5-day recovery period.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.