Effect of atrioventricular interval during pacing or reciprocating tachycardia on atrial size, pressure, and refractory period. Contraction-excitation feedback in human atrium

To determine whether a contraction-excitation feedback mechanism exists in human atrium, we investigated the effects of varying the atrioventricular (AV) interval from 0 to 360 msec during AV pacing at a cycle length of 400 msec on atrial pressure, size, and refractoriness in 10 patients (group 1, without supraventricular tachycardia). The same parameters were determined in another 10 patients (group 2, with different spontaneous AV relations) during AV reciprocating tachycardia or AV nodal reciprocating tachycardia and during high right atrial (RA) pacing at the tachycardia cycle length. In group 1 patients, peak and mean RA pressure, RA effective refractory period (RA-ERP), and left atrial (LA) size all decreased to minimal values at an AV interval of 120 msec and remained low as the AV interval was increased and approached 400 msec. The increase in each of the variables from its lowest to greatest value was as follows: Mean systemic blood pressure, 20.9 +/- 3.1 mm Hg; LA size, 0.55 +/- 0.05 cm; RA peak pressure, 10.4 +/- 1.8 mm Hg; RA mean pressure, 3.5 +/- 0.6 mm Hg; and RA-ERP, 22.5 +/- 3.0 msec, p less than 0.001 for each. The weighted mean correlation coefficient with RA-ERP was significant for RA peak pressure and LA size (p less than 0.001 for each). These same relations were investigated in five patients with the Wolff-Parkinson-White syndrome and AV reciprocating tachycardia and five patients with AV nodal reciprocating tachycardia (group 2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced parasympathetic tone shortens atrial refractoriness in man

The purpose of this study was to determine the effects of enhanced vagal tone on human right atrial refractoriness in 12 patients. A specially built neck collar connected to a vacuum source was placed around the patient's neck and enhanced vagal tone was produced during neck suction using intracollar negative pressures of 50 to 60 mm Hg. Refractory periods were determined with a catheter electrode positioned in the high right atrium near the sinus node. Induced neck suction increased the spontaneous sinus cycle length from 837 +/- 96 to 1.136 +/- 273 ms (p less than 0.001) and shortened the atrial effective refractory period from 241 +/- 24 to 230 +/- 20 ms (p less than 0.01) and the atrial functional refractory period from 272 +/- 32 to 262 +/- 29 ms (p less than 0.01). In 2 of 2 patients, collar-induced decreases in atrial refractoriness and increases in spontaneous cycle length were prevented after atropine (0.03 mg/kg) was given intravenously. It is concluded that enhanced vagal tone mediated through muscarinic receptors shortens atrial refractory periods in man.     

Antiarrhythmic and proarrhythmic properties of diazepam demonstrated by electrophysiological study in humans

We evaluated the electrophysiological parameters before and after the intravenous infusion of diazepam (0.2 mg/kg) in 20 cardiac patients to investigate the drug's antiarrhythmic effect. Diazepam did not significantly change the arterial pressure. After the intravenous infusion of diazepam, the sinus cycle length significantly shortened from 847 +/- 132 to 747 +/- 155 ms (p less than 0.01). No significant change in the maximal sinus node recovery time was noted. The AH interval at the atrial pacing length of 600 ms shortened significantly from 140 +/- 40 to 127 +/- 39 ms (p less than 0.05). However, there was no significant change after the administration of diazepam in the longest atrial pacing rate associated with Wenckebach conduction in the atrioventricular (AV) node, effective and functional refractory periods of the AV node, HV interval, and QRS width during ventricular pacing at the cycle length of 600 ms. The atrial and ventricular effective refractory periods remained unchanged after the administration of diazepam. Six of the eight patients who showed dual AV nodal refractory period curves in the control study did not demonstrate them after diazepam administration by increasing the atrial or AV node effective refractory period. Thus, diazepam showed significant electrophysiological effects of the heart including shortening of the sinus cycle length, improvement in AV node conduction, and no significant effect on the His-Purkinje or intraventricular conduction and refractoriness of the atrium, AV node and ventricle. On the other hand, diazepam may influence the inducibility of supraventricular reentrant tachycardia incorporating the AV node.     

Progressive obstruction of the foramen ovale in patients with left atrioventricular valve atresia

Thirteen patients with left atrioventricular (AV) valve atresia and a normal aortic root were studied to evaluate the status of the interatrial communication with advancing age. Six patients had cardiac catheterization within the first 2 weeks of age; of these, five had repeat studies before 7 months of age. The seven other patients initially underwent catheterization after 2 weeks of age. In the group with catheterization before 2 weeks of age, the mean left atrial pressure was 7.8 +/- 5.5 mm Hg and the left atrial-right atrial mean pressure gradient was 1.7 +/- 2.4 mm Hg. In the combined group of patients with catheterization after 2 weeks of age, the mean left atrial pressure was 25.9 +/- 5.6 mm Hg and the mean left atrial-right atrial pressure gradient was 21.1 +/- 5.1 mm Hg. Seven of the 13 patients have survived and have now reached a median age of 6.5 years. Balloon atrial septostomy was adequate for long-term survival in one patient; all of the others have required surgical atrial septectomy. Progressive obstruction of the foramen ovale is part of the natural history of left AV valve atresia, and obstruction develops despite the absence of a left atrial-right atrial gradient during newborn study. Balloon atrial septostomy is recommended during the neonatal period in all patients with left AV valve atresia, even in the absence of an interatrial gradient. Because early surgical atrial septectomy is usually necessary for long-term survival, these patients should have serial noninvasive evaluation of the patency of the interatrial communication.     

Electrophysiologic effects of diprafenone in supraventricular and ventricular tachycardia

The electrophysiologic effects of diprafenone were evaluated in 31 patients (9 X AV nodal reentrant tachycardia, 9 X Wolff-Parkinson-White syndrome, 4 X paroxysmal atrial fibrillation, 10 X recurrent ventricular tachycardia). Electrophysiologic studies were performed before and after intravenous infusion of 1.5 mg/kg body weight diprafenone in a period of 10 minutes. Diprafenone prolonged the mean RR interval during sinus rhythm from 690 +/- 109 ms to 789 +/- 93 ms and the maximal sinus node recovery time from 1081 +/- 216 ms to 1300 +/- 398 ms (p less than 0.001). The effective refractory period of the right atrium increased from 195 +/- 22 ms to 210 +/- 28 ms (p less than 0.01) and of the right ventricle from 220 +/- 20 ms to 235 +/- 20 ms (p less than 0.001). Diprafenone produced a prolongation of the antegrade effective refractory period of the AV node from 260 +/- 35 ms to 294 +/- 39 ms (p less than 0.01) and of the retrograde effective refractory period from 265 +/- 76 ms to 400 +/- 130 ms (p less than 0.001). The effective refractory periods of the Kent bundle increased: antegrade from 299 +/- 45 ms to 413 +/- 133 ms, retrograde from 252 +/- 33 ms to 286 +/- 169 ms (p less than 0.05). Suppression of inducibility was observed in 12 of 17 patients with supraventricular reentrant tachycardia, in 5 of 8 patients with atrial fibrillation and in 7 of 10 patients with recurrent ventricular tachycardia. The rate of supraventricular tachycardias decreased under the influence of the substance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of refractory periods and conduction velocity during atrial fibrillation using atrial capture in dogs: direct assessment of the wavelength and its modulation by a sodium channel blocker, pilsicainide

OBJECTIVES: The purposes of this study were to measure the atrial refractory period and the conduction velocity (CV) during atrial fibrillation (AF) and to explore the antiarrhythmic mechanism of a sodium channel blocker, pilsicainide, during AF. BACKGROUND: Sodium channel blockers not only decrease the CV, but also prolong the atrial refractory period, particularly during rapid excitation. Because these effects on the wavelength are counteractive and rate dependent, it is critical to measure these parameters during AF. METHODS: In eight dogs, after AF was induced under vagal stimulation, a single extra-stimulus was repeatedly introduced from the left atrium and its capture was statistically determined for each coupling interval. The local CV was also measured during constant capture of the fibrillating atrium by rapid pacing. The same procedure was repeated after pilsicainide administration. RESULTS: Pilsicainide significantly increased the mode of AF intervals from 81 +/- 10 to 107 +/- 16 ms (p < 0.01). While the CV was decreased from 0.9 +/- 0.1 to 0.7 +/- 0.1 m/s (p < 0.02), the effective refractory period during AF was increased from 69 +/- 11 ms to 99 +/- 17 ms (p < 0.01). As a result, the wavelength was significantly increased by pilsicainide from 6.6 +/- 0.9 to 7.6 +/- 1.2 cm (p < 0.05). CONCLUSIONS: During AF, whereas the sodium channel blocker pilsicainide decreases CV, it lengthens the wavelength by increasing the refractory period, an action that is likely to contribute to the drug's ability to terminate the arrhythmia. The direct measurement of refractoriness and CV during AF may provide new insights into the determinations of the arrhythmia and antiarrhythmic drug action.     

Influence of the site of stimulation on atrioventricular nodal refractory periods and the effect of verapamil

The refractory periods of the atrioventricular (AV) node appear dependent on the pattern of AV nodal input. In 21 superfused AV rabbit heart preparations stimulated from each of the 2 principal input regions, crista terminalis or atrial septum, the effect of changing the site of stimulation of the AV nodal refractoriness and the relative effect of verapamil on AV nodal refractoriness was determined. In 6 of 21 preparations the functional AV refractory curve became discontinuous only when stimulation was applied at the atrial septum and suggested dual AV nodal pathways (dual pathways group). In the 15 other preparations no interruption of the curve occurred with either crista terminalis or atrial septal stimulation (normal conduction group). In the normal conduction group, the difference in the effective refractory period of the AV node obtained by crista terminalis vs atrial septal stimulation was not significant (154 +/- 25 vs 150 +/- 28 ms). However, the functional refractory period was significantly longer with crista terminalis vs atrial septal stimulation (232 +/- 19 vs 239 +/- 19 ms, p less than 0.001). After verapamil administration, the effective and functional refractory periods during crista terminalis vs atrial septal stimulation were prolonged to 270 +/- 49 vs 285 +/- 55 ms (p less than 0.01) and 335 +/- 43 vs 351 +/- 41 ms (p less than 0.001), respectively. Thus, the difference in refractory periods associated with changing the stimulation site was exaggerated with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Atrial Pressure Increase on Effective Refractory Period and Vulnerability to Atrial Fibrillation in Patients with Lone Atrial Fibrillation

Background: There is evidence suggesting that atrial fibrillation (AF) may be induced by acute increase of atrial pressure. The aim of the present study was to investigate the effect of alterations in atrial pressure, induced by varying the atrioventricular (AV) interval, on atrial refractoriness, and on the frequency of induction of (AF), in patients with a history of lone atrial fibrillation (LAF).Methods and Results: Twenty-five patients were included in this study. The patients were divided in two groups: the LAF group, and the control group. None of the patients in either group had organic heart disease. Effective refractory period (ERP) and duration of atrial extrastimulus electrogram (A₂) were measured at two right atrial sites (high lateral wall, atrial appendage) during AV pacing (cycle length: 500 msec) with different AV intervals. Peak, minimal and mean atrial pressure increased from 8.57 ± 2.37 to 18.14 ± 4.74 mm Hg, 2 ± 2.23 to 5.14 ± 2.60 mm Hg (p = 0.0001) and from 4.28 ± 1.6 mm Hg to 9.77 ± 2.9 mm Hg (p = 0.001), respectively during AV interval modification. During lateral and atrial appendage pacing, with a progressive decrease of AV interval to 160, 100, 80, 40, 0 msec, the ERP, the dispersion of ERP, functional refractory period (FRP), A2 and latency period (LP) did not change significantly, in both groups. The frequency of induction of AF was not statistically different in both lateral atrial wall and appendage, during pacing in different AV intervals.Conclusions: This study demonstrates that alterations in the intraatrial pressure does not have important effects on atrial refractoriness and does not increase vulnerability to AF in patients with a history of LAF.     

Acute electrophysiologic effects of pirmenol in normal subjects and in patients with Wolff-Parkinson-White syndrome

The acute electrophysiologic effects of pirmenol are reported in 8 normal subjects and in 8 patients with Wolff-Parkinson-White (WPW) syndrome. Standard electrophysiologic testing was performed before and after a 50-mg intravenous bolus and a 60-minute infusion of 150 mg of pirmenol. After pirmenol administration, AH interval, atrial refractory period, atrioventricular (AV) nodal functional refractory period and Wenckebach cycle length did not change; however, sinus cycle length decreased from 743 +/- 169 to 650 +/- 133 ms (p less than 0.001), sinoatrial conduction time from 103 +/- 35 to 78 +/- 37 ms (p less than 0.05) and AV nodal effective refractory period from 308 +/- 51 to 272 +/- 23 ms (p less than 0.01). Pirmenol increased the HV interval from 43 +/- 5 to 48 +/- 6 ms (p less than 0.05) and ventricular functional refractory period from 247 +/- 21 to 260 +/- 21 ms (p less than 0.005). Anterograde effective refractory period of the accessory AV pathway increased in 4 of 6 patients with ventricular preexcitation and retrograde effective refractory period increased in all patients. Pirmenol treatment prolonged the shortest preexcited RR interval from 253 +/- 38 to 459 +/- 19 ms (p less than 0.05) and the average RR interval from 354 +/- 26 to 421 +/- 60 ms (p less than 0.01) during atrial fibrillation in all 6 patients with preexcitation. Pirmenol did not influence the inducibility or cycle length of AV reciprocating tachycardia in the patients with WPW syndrome. The pirmenol infusions were well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic study of the effects of aminophylline and metaproterenol on canine myocardium.

Aminophylline and beta-adrenergic agonists are widely used in the treatment of obstructive lung diseases. It has been suggested that combined aminophylline and beta-agonist therapy may promote the development of atrial and ventricular arrhythmias. The effects of these agents in combination on myocardial conduction and tissue refractoriness have not been documented. We evaluated the electrophysiologic effects of intravenous aminophylline and inhaled metaproterenol on canine myocardium. Aminophylline produced significant decreases from baseline in the AH interval (85 +/- 6.5 [SD] to 63 +/- 4.1 ms [p less than 0.02]), Wenckebach cycle length (WCL) (226 +/- 8.7 to 182 +/- 5.8 ms [p less than 0.02]), and ventricular effective refractory period (VERP) (166 +/- 6.0 to 148 +/- 4.9 ms [p less than 0.01]). Metaproterenol produced similar results, except metaproterenol significantly decreased the atrial effective refractory period (AERP) from 152 +/- 6.6 to 130 +/- 3.2 ms (p less than 0.02), an effect not seen with aminophylline alone. Metaproterenol also produced significantly greater reductions in AH interval and WCL, as well as a greater increase in heart rate than aminophylline did. When compared with aminophylline alone, combined metaproterenol and aminophylline therapy produced significantly greater reductions in the AH interval (63 +/- 4.1 versus 48 +/- 1.2 ms for combined therapy [p less than 0.01]), HV interval (32 +/- 1.2 versus 28 +/- 2.0 ms for combined therapy [p less than 0.02]), WCL (182 +/- 5.8 versus 150 +/- 7.1 ms for combined therapy [p less than 0.02]), and VERP (148 +/- 4.9 versus 132 +/- 2.0 ms for combined therapy [p less than 0.02]). We conclude that both aminophylline and metaproterenol significantly enhance AV nodal and His-Purkinje conduction. Metaproterenol produced significant changes in both atrial and ventricular tissue refractoriness. Metaproterenol produced significantly greater changes than aminophylline alone, and inhaled metaproterenol combined with intravenous aminophylline produced greater changes in AV nodal and His-Purkinje conduction and ventricular refractoriness than did aminophylline alone in a canine model.     

The electrophysiological effects of intravenous magnesium on human sinus node, atrioventricular node, atrium, and ventricle

The effects of intravenously (IV) administered magnesium chloride (MgCl) on electrophysiologic and electrocardiographic variables were studied in 13 patients undergoing a routine electrophysiologic assessment for clinical indications. An infusion of 12 mmol of MgCl was given during a 10-min period and relevant electrophysiologic variables were determined before and after the infusion. Serum Mg levels increased from 0.78 +/- 0.03 (mean +/- SEM) before to 1.52 +/- 0.08 ms after the infusion (p less than 0.0001). Magnesium treatment caused a significant prolongation in PR interval (from 151 +/- 8 to 174 +/- 8 ms, p less than 0.001) as well as in QRS duration (from 90 +/- 4 to 101 +/- 6 ms, p less than 0.05). Likewise, intra-atrial (PA) as well as atrioventricular (AV) nodal (AH) conduction times were significantly prolonged (from 33 +/- 3 to 46 +/- 3 ms, p less than 0.01, and from 85 +/- 6 to 94 +/- 6 ms, p less than 0.05, respectively). Mean effective and functional atrial refractory periods increased (from 228 +/- 8 to 256 +/- 10 ms, p less than 0.01 and from 292 +/- 9 to 320 +/- 11 ms, p less than 0.01, respectively), as did mean AV node functional refractory period (from 399 +/- 29 to 422 +/- 27 ms, p less than 0.02). No significant change occurred with regard to sinus node function (as estimated from heart rate, sinus node recovery time, and calculated sinoatrial conduction time) or ventricular refractoriness. It is concluded that IV Mg has several electrophysiologic effects that may be beneficial in the treatment/prevention of supraventricular tachyarrhythmias.     

Cibenzoline: electrophysiologic effects of a new class I anti-arrhythmia agents in supraventricular tachycardia

Cibenzoline, an imidazoline derivate, is a new class 1 antiarrhythmic agent. The electrophysiologic effects and antiarrhythmic properties of cibenzoline (100 mg i.v.) were evaluated in 22 patients with paroxysmal supraventricular tachycardia: 12x Wolff-Parkinson-White Syndrome, 9x AV nodal reentrant tachycardia, 1x atrial tachycardia. Cibenzoline shortened the sinus cycle length from 742 +/- 103 ms to 661 +/- 87 ms (p less than 0.001) and the sinus node recovery time from 1026 +/- 106 ms to 926 +/- 135 ms (p less than 0.001). The substance lengthened the AH interval from 93 +/- 19 ms to 112 +/- 24 ms (p less than 0.001) and the HV interval from 42 +/- 12 ms to 61 +/- 14 ms (p less than 0.001). The effective refractory periods of the atrium and right ventricle did not change significantly, but the effective refractory period of the AV node in antegrade (269 +/- 42 ms vs 278 +/- 46 ms; p less than 0.05) and retrograde direction (281 +/- 57 ms vs 413 +/- 124 ms; p less than 0.001) increased markedly. Cibenzoline prolonged the effective refractory period of the accessory pathway in retrograde direction from 263 +/- 41 ms to 428 +/- 101 ms (p less than 0.001). The effective refractory period of the antegrade accessory pathway did not change. During atrial stimulation inducibility of the reentrant tachycardia was suppressed in 14 of 22 patients and the inducibility of atrial fibrillation in 7 of 12 patients. The RR interval of the reentrant tachycardia was prolonged from 353 +/- 57 ms to 420 +/- 57 ms (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Diastolic mitral regurgitation with atrioventricular conduction abnormalities: relation of mitral flow velocity to transmitral pressure gradients in conscious dogs

Diastolic mitral regurgitation is a common finding that can be detected with use of Doppler echocardiographic techniques in patients with atrioventricular (AV) conduction abnormalities. With use of simultaneous hemodynamic and Doppler techniques, mitral flow velocity, mitral valve motion and transmitral pressure gradient were studied during 50 cardiac cycles each of spontaneous or atrial paced first- and second-degree AV block in five lightly sedated dogs. Diastolic mitral regurgitation was detected during atrial relaxation on all beats in which ventricular contraction was delayed greater than 190 ms. In all dogs the diastolic regurgitation was associated with a reverse transmitral pressure gradient (3.7 +/- 1.1 mm Hg in first-degree AV block and 3.2 +/- 1.5 mm Hg in second-degree AV block) that occurred primarily as the result of a decrease in atrial pressure with atrial relaxation. These reverse pressure gradients were as large as the maximal forward transmitral gradients in early diastole (2.9 +/- 0.9 mm Hg in first-degree AV block and 3.1 +/- 0.7 mm Hg in second-degree AV block) and larger than the maximal forward pressure gradients at atrial contraction (1.7 +/- 0.5 and 1.4 +/- 0.6 mm Hg, respectively, p less than 0.05). The maximal reverse pressure gradient during atrial relaxation was also as large as the reverse pressure gradient in mid-diastole (2.7 +/- 0.9 and 2.8 +/- 1.0 mm Hg, respectively), associated with deceleration of early diastolic mitral flow. Peak diastolic mitral regurgitation velocity coincided with the maximal reverse transmitral gradient and was usually larger than anterograde mitral flow velocity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of flecainide on the rate dependence of atrial refractoriness, atrial repolarization and atrioventricular node conduction in anesthetized dogs.

Flecainide is effective against certain supraventricular arrhythmias (atrial fibrillation and atrioventricular [AV] node reentrant tachycardia), but its mechanisms of action are unknown. Previous in vitro work suggests that flecainide attenuates rate-dependent action potential duration shortening, producing tachycardia-dependent prolongation of the refractory period. This study was designed to assess whether similar changes occur in vivo and whether the effects of flecainide on AV node conduction depend on heart rate and on direction of propagation (anterograde vs. retrograde). The effects of flecainide at three clinically relevant concentrations were assessed in open chest, morphine-chloralose-anesthetized dogs. Flecainide increased atrial refractory period in a concentration- and rate-related fashion (e.g., dose 3 increased the atrial effective refractory period by 9 +/- 4% at a cycle length of 1,000 ms but by 36 +/- 5% and 55 +/- 10% at a basic cycle length of 400 and 300 ms, respectively; p less than 0.001 for each). Flecainide attenuated the action potential duration accommodation (measured by monophasic action potentials) to heart rate, causing tachycardia-dependent action potential duration prolongation and accounting for most of the rate-dependent atrial effective refractory period changes. Flecainide increased Wenckebach cycle length, but the concentration-response curve was much steeper in the retrograde (slope 41 +/- 7 ms/mumol.liter-1) than in the anterograde direction (17 +/- 4 ms/mumol.liter-1; p less than 0.01), indicating more potent effects on retrograde conduction. The depressant action of the drug on the AV node was also rate dependent, with an effect on the AH interval at a basic cycle length of 400 ms that averaged 1.8, 1.5 and 2 times that at a basic cycle length of 1,000 ms for doses 1 (p less than 0.05), 2 (p less than 0.01) and 3 (p less than 0.001), respectively. Conclusions: 1) Flecainide suppresses atrial action potential duration accommodation to heart rate changes in vivo, leading to rate-dependent atrial effective refractory period prolongation, which may be important in suppressing atrial fibrillation. 2) The drug has frequency- and direction-dependent effects on AV node conduction, which may lead to selective antiarrhythmic actions during AV node reentry.     

Improved method for evaluating ventriculoatrial conduction before implantation of atrial-sensing dual chamber pacemakers

Pacemaker-mediated tachycardia may occur when a spontaneous ventricular premature depolarization is retrogradely conducted to the atrium with a ventriculoatrial (VA) interval that exceeds the atrial refractory period of an atrial-sensing dual chamber pacemaker. Previous methods for evaluating VA conduction have failed to predict clinical occurrences of pacemaker-mediated tachycardia. In this study, maximal VA intervals after ventricular extrastimuli during atrial or atrioventricular (AV) sequential pacing were compared with intervals measured by the standard method of ventricular pacing. VA intervals were 201 +/- 53 ms during ventricular pacing and 224 +/- 52 ms after ventricular extrastimuli during atrial pacing (p = NS). VA intervals were 305 +/- 77 ms after ventricular extrastimuli during AV sequential pacing and were longer than VA intervals during ventricular pacing (p less than 0.001) or after ventricular extrastimuli during atrial pacing (p less than 0.01). Thus, the ventricular extrastimulus technique during AV sequential pacing reveals substantially longer VA intervals than does ventricular pacing and explains why pacemaker-mediated tachycardia might occur when pacemaker atrial refractory periods are designed or programmed according to VA intervals measured only during ventricular pacing.     

Effects of magnesium sulfate on cardiac conduction and refractoriness in humans

Magnesium has been used empirically for several decades in the treatment of atrial and ventricular arrhythmias in patients with normal and decreased serum magnesium levels. However, a systematic evaluation of the effects of magnesium on cardiac conduction and refractoriness in humans has not been described. In this study, the electrocardiographic and electrophysiologic effects of magnesium were determined in 10 patients with normal baseline serum magnesium and other electrolyte levels. Six grams of magnesium sulfate was administered intravenously over 6 minutes followed by a continuous infusion of 1 additional gram over 1 hour. Serum magnesium levels rose significantly from a baseline of 2.0 +/- 0.2 to 5.4 +/- 0.4 mg/dl (p less than 0.001). No significant change occurred in heart rate at rest, or in duration of the QRS complex or QT or QTc intervals during sinus rhythm. There were significant increases in sinus node recovery time (1,000 +/- 211 to 1,106 +/- 223 ms, p less than 0.01) and corrected sinus node recovery time (279 +/- 87 to 336 +/- 104 ms, p less than 0.05). Significant increases occurred in atrioventricular (AV) node conduction time during sinus rhythm (82 +/- 22 to 97 +/- 17 ms, p less than 0.02), in the atrial paced cycle length at which AV node Wenckebach block occurred (350 +/- 46 to 419 +/- 65 ms, p less than 0.01) and in the AV node relative refractory period (397 +/- 27 to 422 +/- 18 ms, p less than 0.05), functional refractory period (395 +/- 41 to 415 +/- 33 ms, p less than 0.05) and effective refractory period (306 +/- 67 to 338 +/- 38 ms, p less than 0.05).     

Acute electrophysiologic effects of inhaled salbutamol in humans

STUDY OBJECTIVES: Although inhaled beta2-agonists are in widespread use, several reports question their potential arrhythmogenic effects. The purpose of this study was to evaluate the cardiac electrophysiologic effects of a single, regular dose of an inhaled beta2-agonist in humans. DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Six patients with bronchial asthma and 12 patients with mild COPD. INTERVENTIONS: All patients underwent an electrophysiologic study before and after the administration of salbutamol solution (5 mg in a single dose). MEASUREMENTS AND RESULTS: Sinus cycle length, sinus node recovery time (SNRT), interval from the earliest reproducible rapid deflection of the atrial electrogram in the His bundle recording to the onset of the His deflection (AH), interval from the His deflection to the onset of ventricular depolarization (HV), Wenckebach cycle length (WCL), atrial effective refractory period (AERP), and ventricular effective refractory period (VERP) were evaluated just before and 30 min after the scheduled intervention. Salbutamol, a selective beta2-agonist, administered by nebulizer had significant electrophysiologic effects on the atrium, nodes, and ventricle. The AH length decreased from 86.1 +/- 19.5 ms at baseline to 78.8 +/- 18.4 ms (p < 0.001), and the WCL decreased from 354.4 +/- 44.2 to 336.6 +/- 41.7 ms (p = 0.001). Salbutamol significantly decreased the AERP and VERP too while leaving the HV unchanged. Additionally, inhaled salbutamol increased heart rate (from 75.5 +/- 12.8 beats/min at baseline to 93.1 +/- 16 beats/min, p < 0.001) and shortened the SNRT (from 1,073.5 +/- 178.7 to 925.2 +/- 204.9 ms, p = 0.001). CONCLUSION: Inhaled salbutamol results in significant changes of cardiac electrophysiologic properties. Salbutamol enhances atrioventricular (AV) nodal conduction and decreases AV nodal, atrial, and ventricular refractoriness in addition to its positive chronotropic effects. These alterations could contribute to the generation of spontaneous arrhythmias.     

The Spatial Dispersion of Atrial Refractoriness and Atrial Fibrillation Vulnerability

The local dispersion of conduction and refractoriness has been considered essential for induction of atrial arrhythmias. This study sought to determine whether a difference of refractoriness and vulnerability for induction of atrial fibrillation between trabeculated and smooth as well as high and low right atrium may contribute to initiation of atrial fibrillation in dogs.In 14 healthy mongrel dogs weighing 22.4 ± 1 kg, closed-chest endocardial programmed stimulation was performed from four distinct right atrial sites. Atrial refractory periods and vulnerability for induction of atrial fibrillation or premature atrial complexes were determined during a basic cycle length of 400 and 300 ms and an increasing pacing current strength.For a pacing cycle length of 300ms, atrial refractory periods were longer on the smooth, as compared to the trabeculated right atrium (102 ± 25 vs. 97 ± 17ms, p < 0.05), whereas for a pacing cycle length of 400ms, there was no significant difference. The duration of the vulnerability zone for induction of atrial fibrillation was longer on the smooth right atrium, for a cycle length of both 400 ms (40 ± 30 vs. 31 ± 22 ms; p < 0.05) and 300 ms (33 ± 25 vs. 23 ± 21 ms; p < 0.01). When comparing high and low right atrium, refractory periods were longer on the the low right atrium, for a cycle length of both 400 ms (111 ± 23 vs. 94 ± 24ms; p < 0.01) and 300 ms (104 ± 20 vs. 96 ± 23ms; p < 0.01). For a pacing cycle length of 300 ms, the duration of the atrial fibrillation vulnerability zone was longer for the high, as compared to the low right atrium (34 ± 22 vs. 22 ± 22, p < 0.01). Seven dogs with easily inducible episodes of atrial fibrillation demonstrated significantly shorter refractory periods as compared to 7 non-vulnerable dogs, regardless of pacing site and current strength.In conclusion, significant differences in refractoriness and vulnerability for induction of atrial fibrillation can be observed in the area of the crista terminalis in healthy dogs. Thus, local anatomic factors may play a role in the initiation of atrial fibrillation.     

Systolic and diastolic dysfunction during atrial pacing in conscious dogs with left ventricular hypertrophy

To determine the extent to which the hypertrophied left ventricle responds to the chronotropic stress induced by graded atrial pacing rates, we studied conscious, chronically instrumented dogs with severe compensated pressure overload left ventricular (LV) hypertrophy induced by aortic banding in puppies 8-10 weeks of age. At 1-2 years, dogs with severe LV hypertrophy (LV free wall/body wt ratio 6.8 +/- 0.6 g/kg) and sham-operated littermates (LV free wall/body wt ratio 4.0 +/- 0.3 g/kg) were instrumented with ultrasonic dimension crystals to measure LV short axis internal diameter and wall thickness, miniature LV pressure transducers, and aortic and LV catheters. During atrial pacing (240 beats/min) in eight control dogs, LV pressure did not change from 119 +/- 2 mm Hg, and mean velocity of circumferential fiber shortening (VCF) did not change from 1.25 +/- 0.09/sec. In seven dogs with LV hypertrophy, atrial pacing (240 beats/min) decreased systolic LV function; that is, LV systolic pressure decreased (p less than 0.01) by 65 +/- 12 from 254 +/- 14 mm Hg, and VCF decreased (p less than 0.01) by 0.19 +/- 0.03 from 0.97 +/- 0.15/sec. Diastolic dysfunction was also observed in the dogs with LV hypertrophy. In the control dogs during atrial pacing (240 beats/min), LV end-diastolic pressure decreased (p less than 0.01) by 8 +/- 1 from 9 +/- 1 mm Hg, end-diastolic stress decreased (p less than 0.01) by 18 +/- 2 from 22 +/- 2 g/cm2, and the radial myocardial stiffness constant did not change from 5.6 +/- 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased dispersion of "refractoriness" in patients with idiopathic paroxysmal atrial fibrillation.

The average interval between local depolarizations during atrial fibrillation, the so-called atrial fibrillation interval, was used as an index for local "refractoriness." This was based on the assumption that during fibrillation, cells are reexcited as soon as their refractory period ends. A very good correlation was found between refractory periods determined with the extrastimulus technique at a basic cycle length of 400 ms and atrial fibrillation intervals measured at the same epicardial sites of the right atrium. This new technique was used to assess dispersion in atrial fibrillation intervals in 10 patients with idiopathic paroxysmal atrial fibrillation and in a control group of 6 patients who were undergoing cardiac surgery. After a routine median sternotomy a multiterminal grid with up to 40 electrodes was placed over the right atrium, and atrial fibrillation was induced by premature stimulation. The average fibrillation interval in the test group, recorded at 247 sites, was 152 +/- 3 ms and that in the control group, recorded at 118 sites, was 176 +/- 8.1 ms (p less than 0.05). Dispersion in atrial fibrillation intervals, defined as the variance of the fibrillation intervals at all the recording sites, was three times larger in the group with paroxysmal atrial fibrillation than in the control group. This study suggests that both a shorter refractory period and a larger dispersion in refractoriness are responsible for the recurrence of atrial fibrillation.