dihydropyridines and Atrial-Fibrillation

Calcium channel antagonists are most frequently prescribed for the treatment of hypertension and the majority specifically inhibit the L-type Ca2+ channel. In order to prevent reflex sympathetic over activity caused by L-type calcium channel antagonists (calcium channel blockers [CCBs]), increasing attention has focused on the blockade of the T-type Ca2+ channel. The T-type Ca2+ channel is found in the kidney and can also appear in the ventricle of the heart when in failure. Therefore, the T-type Ca2+ channel is a possible new target for the treatment of nephropathy and heart failure. In clinical trials, the efficacy and safety of T-type CCBs in hypertension and chronic renal disease have been reported. It is well known that the T-type Ca2+ channel is present in the adult atrium and plays a role in the cardiac pacemaker, but recent experimental studies suggest that this current also promotes electrical remodelling of the atrium. Using efonidipine, a dual L- and T-type CCB, it has been demonstrated that atrial electrical remodelling can be diminished in dogs. Furthermore, the T-type Ca2+ channel has recently been found in the pulmonary veins, contributing to the pulmonary vein pacemaker activity and triggered activity. A variety of drugs having T-type CCB effects have been shown to be effective in the management of atrial fibrillation, suggesting that this channel may be a novel therapeutic target.

Topics: Animals; Atrial Fibrillation; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, T-Type; Dihydropyridines; Drug Delivery Systems; Humans; Nitrophenols; Organophosphorus Compounds

Atrial fibrillation (AF), the most common form of sustained arrhythmia, is associated with a frightening risk of embolic complications, tachycardia-related ventricular dysfunction, and often disabling symptoms. Pharmacologic therapy is the treatment used most commonly to restore and maintain sinus rhythm, to prevent recurrences, or to control ventricular response rate.. This article reviews published data on pharmacologic treatment and discusses alternative systems to classify AF and to choose appropriate pharmacologic therapy.. AF is either paroxysmal or chronic. Attacks of paroxysmal AF can differ in duration, frequency, and functional tolerance. In the new classification system described, 3 clinical aspects of paroxysmal AF are distinguished on the basis of their implications for therapy. Chronic AF usually occurs in association with clinical conditions that cause atrial distention. The risk of chronic AF is significantly increased by the presence of congestive heart failure or rheumatic heart disease. Mortality rate is greater among patients with chronic AF regardless of the presence of coexisting cardiac disease. The various options available for the treatment of chronic AF include restoration of sinus rhythm or control of ventricular rate. Cardioversion may be accomplished with pharmacologic or electrical treatment. For patients in whom cardioversion is not indicated or who have not responded to this therapy, antiarrhythmic agents used to control ventricular response rate include nondihydropyridine calcium antagonists, digoxin, or beta-blockers. For patients who are successfully cardioverted, sodium channel blockers or potassium channel blockers such as sotalol, amiodarone, or a pure class III agent such as dofetilide, a selective potassium channel blocker, may be used to prevent recurrent AF to maintain normal sinus rhythm.. The ultimate choice of the antiarrhythmic drug will depend on the presence or absence of structural heart disease. An additional concern with chronic AF is the risk of arterial embolization resulting from atrial stasis and the formation of thrombi. In patients with chronic AF the risk of embolic stroke is increased 6-fold. Therefore anticoagulant therapy should be considered in patients at high risk for embolization. Selection of the appropriate treatment should be based on the concepts recently developed by the Sicilian Gambit Group (based on the specific channels blocked by the antiarrhythmic agent) and on clinical experience gained over the years with antiarrhythmic agents. For example, termination of AF is best accomplished with either a sodium channel blocker (class I agent) or a potassium channel blocker (class III agent). In contrast, ventricular response rate is readily controlled by a beta-blocker (propranolol) or a calcium channel blocker (verapamil). Alternatively, antiarrhythmic drug therapy may be chosen based on the Vaughan-Williams classification, which identifies the cellular electrophysiologic effects of the drug.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Digoxin; Dihydropyridines; Drug Administration Routes; Electrocardiography; Embolism; Heart Rate; Humans; Practice Guidelines as Topic; Prognosis; Propranolol; Secondary Prevention; Tachycardia, Paroxysmal; Verapamil

The history of the treatment of heart failure may be divided into three stages, the consequences of different conceptions of the physiopathology of the disease, with diuretics to counteract salt and water retention, vasodilators to improve conditions of cardiac load, angiotensin converting enzyme inhibitors to limit the effect of neurotumoral and sympathetic activation. There are two main reasons for using calcium antagonist in heart failure, the first being arterial vasodilatation leading to improve systolic function and the second being the beneficial effect on ventricular relaxation. However, their use has been controversial because of the results obtained with the first generation of these drugs. New molecules derived from dihydropyridine have been developed. Clinical trials with these second generation calcium antagonists are analysed.

Topics: Animals; Atrial Fibrillation; Calcium Channel Blockers; Dihydropyridines; Felodipine; Heart Failure; Hemodynamics; Humans; Systole; Ventricular Function, Left

Mega trials of rhythm vs rate control could not demonstrate the usefulness of available antiarrhythmic drugs, so a more effective and safer therapy for atrial fibrillation (AF) is now required. One candidate is the so-called "upstream therapy", which refers to the blockade of upstream modifying elements (renin - angiotensin system, cathecholamines, oxidative stress etc) that contribute to the arrhythmogenic substrate.. The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is a randomized comparative evaluation of an angiotensin II type 1 blocker (candesartan) and a dihydropiridine calcium blocker (amlodipine), both combined with antithrombotic therapy, as an antiarrhythmic therapy for the treatment of paroxysmal AF (PAF) associated with hypertension. To test the usefulness of this therapy, this study will reveal the recurrence rate of asymptomatic as well as symptomatic PAF during 1-year of treatment with candesartan or amlodipine, using daily transtelephonic monitoring.. The J-RHYTHM II study will follow 400 patients with PAF and hypertension who were treated at approximately 50 sites throughout Japan, and will provide clinically important information.

Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Atrial Fibrillation; Benzimidazoles; Biphenyl Compounds; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension; Secondary Prevention; Tetrazoles

The modification of AV conduction induced by 4 mg b.i.d. of lacidipine (L), a new calcium antagonist, was assessed by studying the changes in ventricular rhythm in 10 patients with stable chronic atrial fibrillation (mean age 71 +/- 15) by daily Holter recordings. The study was single blind versus placebo (P), nifedipine (N) 10 mg b.i.d. and for five patients diltiazem (D) 120 mg b.i.d. Five or seven consecutive 24 hours Holter were recorded in the following order: P, P, N or L, P, N or L, D, D. For each hour, an RR histogram was drawn and the 10 per cent and 90 per cent values of the cumulative cycle length curve were computed, as were the total number of QRS, and the mean value of RR intervals. The correlation coefficient between the number of QRS from the same hour on different days, the Student t test between the mean hourly RR interval values and the comparison between the histograms did not demonstrate a significant difference between the placebo, the nifedipine and the lacidipine periods. The only significant changes were induced by diltiazem (p less than 0.01), with a significant prolongation of the RR intervals. This suggests that lacidipine, like nifedipine, has no effect on AV conduction.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Calcium Channel Blockers; Dihydropyridines; Drug Evaluation; Electrocardiography, Ambulatory; Female; Heart Conduction System; Humans; Male

Outside of clinical trials, the prophylactic effect of dihydropyridine calcium channel blockers (CCBs) on ischemic events in patients with nonvalvular atrial fibrillation (NVAF) has not been confirmed. We compared the effect of dihydropyridine CCBs on ischemic events in anticoagulated NVAF patients. We conducted a multicenter historical cohort study at 71 centers in Japan. The inclusion criterion was taking vitamin K antagonists for NVAF. The exclusion criteria were mechanical heart valves and a history of pulmonary thrombosis or deep vein thrombosis. Consecutive patients (N = 7826) were registered in February 2013 and were followed until February 2017. The primary outcomes were ischemic events and ischemic strokes; the secondary outcomes were all-cause mortality, major bleeding, and hemorrhagic strokes. The mean patient age was 73 years old, and 67% of the patients were male. Seventy-eight percent of the patients had hypertension, and dihydropyridine CCBs were used by 2693 (34%) patients (CCB group). The cumulative incidences of ischemic events and ischemic strokes at 4 years in the CCB and No-CCB groups were 5.9% vs. 5.2% and 5.6% vs. 4.8%, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of the CCB group for ischemic events and ischemic strokes were 1.22 (0.95-1.57) and 1.32 (1.02-1.71), respectively; the adjusted HRs (95% CIs) of the CCB group for all-cause mortality, major bleeding, and hemorrhagic strokes were 0.85 (0.69-1.04), 1.12 (0.92-1.35), and 1.08 (0.62-1.88), respectively. Dihydropyridine CCB use by anticoagulated NVAF patients significantly increased ischemic strokes in a real-world setting.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Calcium Channel Blockers; Cohort Studies; Dihydropyridines; Female; Hemorrhage; Hemorrhagic Stroke; Humans; Ischemic Stroke; Male; Stroke

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Dihydropyridines; Humans; Sympathetic Nervous System

Autonomic dysfunction can promote atrial fibrillation (AF) and results from AF-related remodelling. N-type Ca2+-channels (NTCCs) at sympathetic nerve terminals mediate Ca2+-entry that triggers neurotransmitter release. AF-associated remodelling plays an important role in AF pathophysiology but the effects of NTCC inhibition on such remodelling is unknown. Here, we investigated the ability of a clinically available Ca2+-channel blocker (CCB) with NTCC-blocking activity to suppress the arrhythmogenic effects of AF-promoting remodelling in dogs.. Mongrel dogs were kept in AF by right atrial tachypacing at 600 bpm. Four groups were studied under short-term AF (7 days): (i) Shams, instrumented but without tachypacing (n = 5); (ii) a placebo group, tachypaced while receiving placebo (n = 6); (iii) a control tachypacing group receiving nifedipine (10 mg orally twice-daily; n = 5), an L-type CCB; and (iv) a cilnidipine group, subjected to tachypacing and treatment with cilnidipine (10 mg orally twice-daily; n = 7), an N-/L-type CCB. With cilnidipine therapy, dogs with 1-week AF showed significantly reduced autonomic changes reflected by heart rate variability (decreases in RMSSD and pNN50) and plasma norepinephrine concentrations. In addition, cilnidipine-treated dogs had decreased extracellular matrix gene expression vs. nifedipine-dogs. As in previous work, atrial fibrosis had not yet developed after 1-week AF, so three additional groups were studied under longer-term AF (21 days): (i) Shams, instrumented without tachypacing or drug therapy (n = 8); (ii) a placebo group, tachypaced while receiving placebo (n = 8); (iii) a cilnidipine group, subjected to tachypacing during treatment with cilnidipine (10 mg twice-daily; n = 8). Cilnidipine attenuated 3-week AF effects on AF duration and atrial conduction, and suppressed AF-induced increases in fibrous-tissue content, decreases in connexin-43 expression and reductions in sodium-channel expression.. Cilnidipine, a commercially available NTCC-blocking drug, prevents AF-induced autonomic, electrical and structural remodelling, along with associated AF promotion.

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Function, Left; Atrial Remodeling; Calcium Channel Blockers; Calcium Channels, N-Type; Calcium Signaling; Connexin 43; Dihydropyridines; Disease Models, Animal; Dogs; Fibrosis; Heart Atria; Heart Rate; Presynaptic Terminals; Sodium Channels; Sympathetic Nervous System

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Fibrillation; Calcium Channel Blockers; Clinical Trials as Topic; Dihydropyridines; Drug Combinations; Enalapril; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardial Ischemia

The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial compared the dihydropyridine T/L-type calcium channel blocker benidipine-based therapies when combined with an angiotensin receptor blocker (ARB), a β-blocker (BB) or a thiazide diuretic (TD). The results suggested that benidipine combined with a BB appeared to be less beneficial in reducing the risk of stroke compared with the benidipine-TD combination (hazard ratio (HR): 2.31, P=0.0109). We further evaluated the treatment effects on different stroke subtypes among the three benidipine-based regimens. The COPE trial was an investigator-initiated, multicenter study with PROBE design. Patients with atrial fibrillation or flutter were excluded from the study. All stroke events were subclassified with the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) criteria. The total incidence of stroke was 4.7, hemorrhagic stroke was 1.6 and ischemic stroke was 2.5 per 1000 person-years. The incidence of lacunar stroke was 1.1, large-artery stroke was 0.6, cardioembolic stroke was 0.3, unknown ischemic type was 0.6 and transient ischemic attack was 0.6 per 1000 person-years. Although few differences in stroke subtypes were observed among the three treatment groups, multi-adjusted HRs for the incidence rates of all types of stroke, hemorrhagic stroke and ischemic stroke were significantly higher with the benidipine-BB regimen than with the benidipine-TD regimen. The incidence of both hemorrhagic and ischemic stroke in the benidipine-ARB regimen was not different compared with the other two treatment regimens. This prespecified sub-analysis suggested that a blood pressure-lowering therapy with a benidipine-TD regimen might be beneficial for hypertensive patients to prevent both hemorrhagic and ischemic stroke.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Atrial Fibrillation; Atrial Flutter; Blood Pressure; Brain Ischemia; Dihydropyridines; Diuretics; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Rate; Humans; Hypertension; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Risk Factors; Stroke; Survival Analysis; Vasodilator Agents

We report the case of a patient seen at the outpatient clinic for a first episode of atrial fibrillation. We discussed the steps of the treatment including anticoagulation, rate and rhythm control.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Dihydropyridines; Electric Countershock; Electrocardiography; Humans; Male; Treatment Outcome

The loss of atrial contractile function after cardioversion of atrial fibrillation (AF) contributes to the thromboembolic risk associated with AF. The newly developed blocker of the transient outward current (I(to)) and ultrarapid delayed rectifier current (I(Kur)) AVE0118 prolongs atrial action potential duration and might therefore enhance atrial contractility. We compared the ability of AVE0118 to restore atrial contraction after cardioversion of AF with the efficacy of conventional positive inotropic compounds in the goat model of AF.. Eighteen goats were chronically instrumented with epicardial electrodes, a pressure transducer in the right atrium, and piezoelectric crystals to measure right atrial diameter. Atrial contractility and refractoriness and QT duration were measured before and after 1 week (3 to 8 days) of AF induced by repetitive burst pacing. The measurements were repeated after administration of digoxin (0.02 mg/kg), dobutamine (5 microg x kg(-1) x min(-1)), the Ca2+ sensitizer EMD57033 (1 mg x kg(-1) x min(-1)), the L-type Ca2+ channel agonist BayY5959 (0.1 mg x kg(-1) x min(-1)), and AVE0118 (0.01 to 0.2 mg x kg(-1) x min(-1)). The effect of AVE0118 on the configuration of atrial monophasic action potentials was determined for comparison. After 1 week of AF, atrial contractility during sinus rhythm or slow atrial pacing was reduced to <10%. Digoxin and dobutamine failed to increase atrial contractility. EMD57033 restored 41% and BayY5959 restored 48% of atrial contractility at baseline. BayY5959 significantly prolonged QT duration by 24.7%. AVE0118 enhanced atrial contraction to 156% of the baseline value. The positive inotropic effect was accompanied by a pronounced prolongation of atrial action potential duration and refractoriness, whereas QT duration remained unchanged.. Conventional positive inotropic drugs showed limited effect on atrial contractility after cardioversion of AF or produced QT prolongation. In contrast, the I(to)/I(Kur) blocker AVE0118 fully restored atrial contraction without proarrhythmic effects on the ventricle.

Topics: Action Potentials; Animals; Atrial Fibrillation; Atrial Function, Right; Biphenyl Compounds; Cardiotonic Agents; Delayed Rectifier Potassium Channels; Digoxin; Dihydropyridines; Disease Models, Animal; Dobutamine; Electric Countershock; Electrocardiography; Goats; Myocardial Contraction; Potassium Channel Blockers; Potassium Channels, Voltage-Gated; Quinolines; Thiadiazines

We encountered a 91-year-old woman with atrial fibrillation complicating bradycardia while she was receiving therapy with an L/N-type calcium channel blocker, cilnidipine, for hypertension, which is an unusual observation for the dihydropyridine class of calcium channel blockers. Therefore, we compared the dromotropic effect of cilnidipine with that of an L-type calcium channel blocker, nicardipine, which has a similar hypotensive activity. The canine isolated, blood-perfused atrioventricular node preparation was used. Cilnidipine as well as nicardipine slowed atrioventricular nodal conduction in a dose-related manner. However, the dromotropic action of cilnidipine was about five times less potent than that of nicardipine. These experimental results may suggest that we experienced an atypical clinical event of cilnidipine in a very old woman; otherwise one can speculate that the N-type calcium channel inhibitory component of cilnidipine might have played a role in exerting the negative dromotropic effect in this patient.

Topics: Aged; Analysis of Variance; Animals; Atrial Fibrillation; Bradycardia; Calcium Channel Blockers; Dihydropyridines; Dogs; Electrocardiography; Female; Humans; Hypertension; Nicardipine

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.

Topics: Administration, Oral; Animals; Atrial Fibrillation; Atrioventricular Node; Calcium; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, T-Type; Cardiac Pacing, Artificial; Dihydropyridines; Dogs; Electrophysiology; Forecasting; Heart Atria; Japan; Male; Nitrophenols; Organophosphorus Compounds; Refractory Period, Electrophysiological; Research Design; Time Factors; Verapamil

The mechanisms of the atrial contractile dysfunction induced by atrial fibrillation (AF) are not completely understood. In particular, the relation between the atrial dysfunction and electrical remodeling has not yet been studied.. Seven goats were chronically instrumented with electrodes sutured to the atria and with ultrasonic piezoelectric crystals to record the atrial diameters. A pressure transducer was implanted in the right atrium. After 5 minutes, 3 hours, and throughout the first 5 days of artificially maintained AF, atrial contractile function was measured and the atrial effective refractory period (AERP) was monitored for comparison. Also, the positive inotropic effects of the L-type Ca2+-channel agonist BayY5959 and short trains of rapid atrial pacing were studied. After resumption of sinus rhythm, the recovery of atrial contractile function was followed. After 5 minutes of AF, atrial contractility was decreased by approximately 55% but recovered completely within 10 minutes. Five days of AF nearly completely abolished the atrial contractile function, and recovery took 2 days. During the first days of AF, the development of the contractile dysfunction followed the same time course as the shortening of AERP (electrical remodeling). In remodeled atria, BayY5959 increased atrial contractility to the same extent as it prolonged AERP. The inotropic effect of short trains of rapid atrial pacing was similar in normal and remodeled atria.. Depending on the duration of AF, different mechanisms contribute to the AF-induced atrial hypocontractility. Atrial contractile remodeling during several days of AF goes hand in hand with electrical remodeling and might be caused by a reduction of the L-type Ca2+-current.

Topics: Adaptation, Physiological; Animals; Atrial Fibrillation; Calcium Channel Agonists; Cardiac Pacing, Artificial; Dihydropyridines; Electric Conductivity; Electrophysiology; Goats; Heart Atria; Kinetics; Myocardial Contraction; Periodicity; Refractory Period, Electrophysiological

Electrical remodeling as well as atrial contractile dysfunction after the conversion of atrial fibrillation (AF) to sinus rhythm (SR) are mainly caused by a reduction of the inward L-type Ca(2+) current (I(CaL)). We investigated whether the expression of L-type Ca2+-channel subunits was reduced in atrial myocardium of AF patients.. Right atrial appendages were obtained from patients undergoing coronary artery bypass graft surgery (CAD, n = 35) or mitral valve surgery (MVD, n = 37). Seventeen of the CAD patients and 18 of the MVD patients were in chronic (>3 months) AF, whereas the others were in SR. The protein expression of the L-type Ca2+-channel subunits alpha1C and beta2 was quantified by western blot analysis. Furthermore, we measured the density of dihydropyridine (DHP)-binding sites of the L-type Ca2+ channel using 3H-PN220-100 as radioligand.. Surprisingly, the alpha1C and the beta2-subunit expression was not altered in atrial myocardium of AF patients. Also, the DHP-binding site density was unchanged.. The protein expression of the L-type Ca2+-channel subunits alpha1C or beta2 is not reduced in atrial myocardium of AF patients. Therefore, the reduced I(CaL) might be due to downregulation of other accessory subunits (alpha2delta), expression of aberrant subunits, changes in channel trafficking or alterations in channel function.

Topics: Animals; Atrial Fibrillation; Binding Sites; Calcium Channels, L-Type; Chronic Disease; Dihydropyridines; Down-Regulation; Humans; Protein Binding; Rabbits

We have shown that rapid atrial activation, as occurs during atrial fibrillation (AF), reduces L-type Ca2+ current (ICa) and that this is the principal mechanism of the action potential duration and refractoriness changes that characterize tachycardia-induced atrial remodeling. The present study was designed to determine whether atrial tachycardia alters biochemical indices of the number of L-type Ca2+ channels and/or of the number and binding affinity of beta-adrenergic receptors.. In canine atrial sarcolemmal preparations, the number and binding affinity of dihydropyridine receptors were determined with the use of 3H-nitrendipine and that of beta-adrenergic receptors with 125I-iodocyanopindolol. Results were obtained with preparations from dogs paced at 400/min for 1 (P1, n = 20), 7 (P7, n = 9), and 42 (P42, n = 9) days, and compared with observations in sham-operated controls (P0, n = 14).. Pacing reduced the Bmax of dihydropyridine receptors, from 157 +/- 18 fmol/mg (P0) to 116 +/- 9 fmol/mg (P1, P < 0.05), 100 +/- 14 fmol/mg (P7, P < 0.05) and 94 +/- 9 fmol/mg (P42, P < 0.01). The affinity of dihydropyridine receptors was unchanged, with the Kd averaging 711 +/- 102 pM. 656 +/- 74 pM, 633 +/- 155 pM and 585 +/- 92 pM in P0, P1, P7 and P42 dogs. Neither Bmax nor Kd of beta-adrenergic receptors was altered by rapid pacing. Values of Bmax of dihydropyridine receptors correlated with atrial ICa current density (r2 = 0.95) and ERP (r2 = 0.99).. Rapid atrial activation results in downregulation in the number of dihydropyridine receptors without altering the number or affinity of beta-adrenergic receptors. The reductions in ICa that play an important role in the atrial electrical remodeling by which 'AF begets AF' appear to be due at least in part to a decrease in the number of L-type Ca2+ channels in cardiac cell membranes.

Topics: Adrenergic beta-Antagonists; Analysis of Variance; Animals; Atrial Fibrillation; Binding Sites; Calcium; Calcium Channel Blockers; Calcium Channels; Cardiac Pacing, Artificial; Dihydropyridines; Dogs; Female; Iodocyanopindolol; Linear Models; Male; Myocardium; Nitrendipine; Receptors, Adrenergic, beta; Sarcolemma; Statistics, Nonparametric