Electrophysiologic effects of the levo- and dextrorotatory isomers of sotalol in isolated cardiac muscle and their in vivo pharmacokinetics

Dl-sotalol is a specific beta-adrenergic blocking agent that markedly lengthens cardiac action potential duration. To determine whether d-sotalol, with little or no beta-blocking effect, also lengthens repolarization, standard microelectrode studies were used to determine the electrophysiologic properties of dl-sotalol and its stereoisomers in isolated rabbit and canine myocardial fibers. D- and l-sotalol produced concentration-dependent increases in action potential duration to 50% (APD50) and 90% (APD90) repolarization, respectively, and in the effective refractory period without changes in the maximal rate of rise of action potential. In rabbit sinoatrial node, d- and l-sotalol produced concentration-dependent increases in spontaneous sinus cycle length (29 and 35%, respectively) by lengthening the action potential duration (by 58 and 55%) without effect on phase 4 depolarization. At the highest concentration (27.2 micrograms/ml), d- and l-sotalol prolonged APD90 (by 38 and 54%, respectively, in Purkinje fibers and by 32 and 34% in ventricular muscle) and effective refractory period (by 49 and 49% in Purkinje fibers and 29 and 40% in ventricular muscle). The effects of the two isomers were not significantly different. At the middle concentration (2.7 micrograms/ml), d-sotalol, unlike l-sotalol, had no beta-adrenergic blocking effect, but the electrophysiologic effects of dl-, d- and l-sotalol were indistinguishable. The data indicate that d-sotalol is equipotent with l-sotalol in lengthening the action potential duration and effective refractory period in cardiac muscle, an action unrelated to adrenergic antagonism or pharmacokinetic differences between the stereoisomers.     

Efficacy, safety, and tolerance of d-sotalol in patients with refractory supraventricular tachyarrhythmias

The efficacy, safety, and electrophysiologic effects of intravenous and oral d-sotalol, an investigational class III antiarrhythmic agent, are not yet well characterized. We evaluated the electrophysiologic, antiarrhythmic, and hemodynamic effects of d-sotalol infusion (1.5 to 2.75 mg/kg) and of chronic oral therapy (200 to 400 mg bid) in 10 patients with chronic, paroxysmal supraventricular tachyarrhythmias refractory to 5 +/- 2 standard agents. Four patients had paroxysmal supraventricular tachycardia (PSVT), four had paroxysmal atrial fibrillation, two had atrial flutter, and one had nonparoxysmal reciprocating junctional tachycardia (NPRJT). PSVT was inducible or spontaneously present in 4 of 4 before d-sotalol. After intravenous d-sotalol PSVT was noninducible in three patients and slowed by 40% in one. Atrial fibrillation was inducible or spontaneously present in 4 of 4 before therapy. After intravenous d-sotalol, one became noninducible, and three achieved rate-slowing (the mean falling from 69 to 61 bpm). In one patient, atrial flutter became noninducible; in another, d-sotalol slowed the rate of atrial flutter by 28%. D-sotalol restored sinus rhythm in the patient with NPRJT. Intravenous d-sotalol increased the sinus cycle length; the QTc, PR, and AH intervals; and the AV nodal functional refractory period, the AV nodal effective refractory period; and the right ventricular effective refractory period significantly. The atrial effective refractory period, sinoatrial conduction time, and corrected sinus recovery time tended to increase, but did not reach statistical significance. The QRS, PA, and HV intervals did not change. Mean BP fell 13.4 +/- 9.2% after intravenous d-sotalol, but no adverse symptoms developed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of bepridil and diltiazem on ventricular repolarization in angina pectoris

To examine the time-course and potential predictors of prolongation of ventricular repolarization with the calcium antagonist bepridil, the effects of bepridil (300 to 500 mg/day; n = 45) and diltiazem (180 to 300 mg/day; n = 42) on QT and QTc interval duration were analyzed in a randomized double-blind study in patients with angina pectoris. Electrocardiograms were recorded before and 14, 28, 70 and 112 days after treatment was begun. After 14 days, bepridil prolonged QT interval by 26 +/- 35 ms (range, -60 to 120 ms) and QTc (Bazett's formula) by 17 +/- 33 ms (range, -73 to 107 ms) compared to baseline (both p less than 0.05). QT or QTc did not significantly increase thereafter. However, among the 30 patients who had less than 40 ms QTc prolongation at day 14 compared with baseline, 13 (43%) exceeded this limit on at least 1 of the following visits. Diltiazem did not significantly alter QT or QTc intervals. The absolute change in QTc interval from baseline observed after 14 days of bepridil therapy was inversely proportional to the baseline QTc interval (r = -0.68; n = 42; p less than 0.001). The degree of bepridil-induced QTc prolongation on day 14 correlated with pretreatment RR interval (r = 0.36; n = 42; p less than 0.02). In conclusion, chronic administration of bepridil but not of diltiazem prolongs ventricular repolarization in patients with angina pectoris. The overall effects of bepridil therapy on QT and QTc intervals can be assessed by an electrocardiogram recorded after 14 days of treatment but subsequent measurements may be required in individual patients. A short baseline QTc interval and a slow initial heart rate may be potentially useful predictors of a greater QTc prolongation with bepridil.     

Electrophysiology and long-term efficacy of pentisomide in patients with supraventricular tachycardia.

The electrophysiologic effects of pentisomide were investigated after intravenous (5 mg/kg) and oral (900-1200 mg three times a day) application in 9 patients with drug refractory atrioventricular nodal tachycardia and 6 patients with orthodromic atrioventricular re-entrant tachycardia. Pentisomide did not change sinus cycle length, effective refractory period of the right ventricle and the atrioventricular node. AH, HV interval, effective refractory period of the right atrium, QRS duration and QTc duration were (p less than or equal to 0.01) increased. Tachycardia cycle length was only increased after intravenous application of pentisomide, antegrade effective refractory periods of the accessory pathways and shortest fully pre-excited R-R intervals during atrial fibrillation were increased after the oral treatment phase (p = 0.054). Intravenous pentisomide prevented tachycardia in 6/9 patients with atrioventricular nodal tachycardia and in 2/6 patients with atrioventricular re-entrant tachycardia. If intravenous pentisomide did not prevent induction of the tachycardia, oral pentisomide was not effective either. During long-term follow-up 2/7 patients with atrioventricular nodal tachycardia and 1/4 patient with atrioventricular re-entrant tachycardia had a recurrence. Long-term treatment with pentisomide had to be discontinued because of possible side effects in 2 patients. It is concluded, that the electrophysiological effects of pentisomide are similar to those of flecainide and propafenone.     

Attenuation of the rise in extracellular potassium concentration during myocardial ischaemia by d.l-sotalol and d-sotalol

STUDY OBJECTIVE--The aim was to study the effects of d.l-sotalol, d-sotalol or atenolol on the rate of rise of extracellular potassium concentration [( K+]o) and the electrophysiological changes that occur during myocardial ischaemia. DESIGN--The study was performed in isolated, arterially perfused interventricular septa from rabbit. Six septa were treated with d.l-sotalol 10(-4) mol.litre-1, six with d-sotalol 10(-4) mol.litre-1, six with atenolol 10(-5) mol.litre-1, and there were seven untreated controls. At these concentrations d.l and d-sotalol are equipotent in their class III effect, though d-sotalol has only 7% of the beta blocking activity of the racemic form, and atenolol is equipotent in its beta blocking activity to d.l-sotalol. [K+]o and electrophysiological variables were compared before and during a 30 min period of global zero flow ischaemia. MEASUREMENTS AND MAIN RESULTS--Prior to ischaemia [K+]o, measured using potassium sensitive valinomycin electrodes, was similar in all the groups. [K+]o rose during ischaemia in all the groups, and at 30 min was 13.0 (SEM 0.7) mmol.litre-1 in the control group which was not different from 12.7(0.5) mmol.litre-1 in the atenolol group. In the d.l and d-sotalol groups the increases were markedly attenuated, reaching 9.2(1.0) and 8.8(0.7) mmol.litre-1 respectively. During ischaemia the class III effect of d.l and d-sotalol was lost within 6 min though the fall in maximum upstroke velocity of the action potentials (dV/dtmax) and the extent of resting membrane potential (Em) depolarisation were less in comparison to the control and atenolol groups. CONCLUSIONS--The results indicate an attenuation by sotalol of the ischaemic rise in [K+]o, with preservation of dV/dtmax and Em, despite the loss of an effect on action potential duration. This potentially antiarrhythmic effect of sotalol in ischaemic myocardium is attributable to a direct membrane effect rather than beta adrenoceptor antagonism.     

Electrophysiological effects of intravenous magnesium sulfate in man

Magnesium salts have been used for many years to correct a wide variety of arrhythmias. A few experimental studies have been devoted to their electrophysiological effects, but these remain poorly documented in man, hence this study. An electrophysiological investigation was conducted in 24 patients before, and immediately after a bolus intravenous injection of magnesium sulphate in doses of 1.5 g to 12 patients (group I) and 3 g to 12 other patients (group II), followed by a continuous infusion at the rate of 1 mg/min. The drug had no influence on heart rate, duration of QRS, QT and QTc intervals and ventricular refractory period. A small, but statistically significant prolongation of HV (from 57 to 59 ms, p less than 0.05) was observed in group II. Analysis of the results in group I revealed a moderate but significant prolongation of the PR and AH intervals. The electrophysiological effects were distinctly more pronounced in group II patients, with significant prolongation of: PR and AH intervals, effective refractory period of the right atrium and AV node, Wenckebach's point, corrected sinus node recovery time and sinoatrial conduction time. These results demonstrate that magnesium sulphate principally acts on the sinus node, the AV node and the atrium, suggesting a blocking effect on calcium channels.     

Distribution of local repolarization changes produced by efferent vagal stimulation in the canine ventricles

The purpose of this study was to compare the distribution of effects of right and left efferent vagal stimulation on ventricular recovery properties in the in situ heart. To measure these effects in many areas simultaneously, local repolarization changes (local QT intervals) were recorded with bipolar electrodes in nine ventricular sites from 38 anesthetized dogs. In initial experiments, this method was shown to correlate with effective refractory period changes measured in the same test site after QT recording; vagal nerve stimulation prolonged the local QT interval by 1 ms for each 0.82 ms prolongation in effective refractory period (r = 0.87). Simultaneous local QT recordings during vagal nerve stimulation demonstrated uniform prolongation with two exceptions. First, left vagal efferent stimulation prolonged local QT interval in the posterior left ventricular base more than did right vagal stimulation (5.9 +/- 1.0 mean +/- standard error of the mean versus 3.7 +/- 0.9%, p less than 0.05). This probably resulted from an interaction with the left sympathetic nerves because left stellate ganglionectomy or norepinephrine infusion eliminated differences between effects of right and left vagal stimulation. Second, it was also found that vagal stimulation from either side did not prolong local QT interval time in the anterior right ventricle despite attempts to augment vagal effects with bilateral vagal stimulation alone or during isoproterenol or physostigmine administration. These regional differences in ventricular repolarization exhibited in response to efferent vagal nerve stimulation in the dog may provide a basis for understanding how autonomic influences could contribute to the genesis of ventricular arrhythmias.     

Rate dependence of sotalol-induced prolongation of ventricular repolarization during exercise in humans.

Studies in animals have shown that drug-induced action potential prolongation with class III antiarrhythmic agents increases with slow pacing rates. We studied the physiological rate dependence of sotalol effects on ventricular repolarization, measured as QT interval duration on the surface electrocardiogram at rest and during a maximal exercise test, in 10 normal volunteers. In a randomized, crossover study, three dosages of sotalol (160 mg/24 hr, 320 mg/24 hr, and 640 mg/24 hr) were administered during 4 days to each subject. In a control period, no drug was administered. During each period, 50-100 QT intervals were measured over a wide range of RR intervals recorded at rest and during the course of a maximal exercise test. Plasma sotalol concentration and beta-adrenoceptor blockade (percent reduction in peak exercise heart rate from control) were also measured. The QT-versus-RR relation was fitted to several formulas, and the overall best fit was used to calculate QT interval duration normalized for a heart rate of 60 beats/min (QTc) and to analyze the rate dependence of QT prolongation with sotalol. Sotalol-induced beta-adrenoceptor blockade and QTc prolongation were dose and concentration dependent. Sotalol reduced peak exercise heart rate by 13.8 +/- 7% at the dosage of 320 mg/24 hr and by 25.4 +/- 8% at the dosage of 640 mg/24 hr (both p less than 0.01). Sotalol prolonged QTc interval by 5.8 +/- 3.7% and 11.8 +/- 3% at these respective dosages (both p less than 0.01). The concentration of sotalol required to produce minimal (mean QTc prolongation, 5.6%; confidence interval, 0-11.2%) QTc prolongation (680 ng/ml) tended to be lower than that required for minimal (mean percent reduction in maximal exercise heart rate, 13.9%; confidence interval, 0-27.8%) beta-blockade (840 ng/ml). QT prolongation with sotalol increased with increasing RR intervals (i.e., decreasing heart rate) at all dosages. QT prolongation became statistically significant for RR of 800 msec or more at all dosages and for RR intervals of 600 msec or more at the dosage of 640 mg/24 hr. This rate dependence altered the relation between QT interval duration and sotalol plasma concentrations. These results suggest that sotalol prolongs QTc interval in humans at dosages and concentrations similar to those required to produce beta-adrenoceptor blockade, QT prolongation with sotalol is more pronounced when heart rate decreases and is not apparent during exercise-induced tachycardia, and the relation between QT prolongation with sotalol and plasma concentrations of the drug depends on the heart rate at which measurements are made.     

Impact of methadone treatment on cardiac repolarization and conduction in opioid users

We prospectively assessed the effect of oral methadone on the corrected QT interval (QTc) among 160 patients free of structural heart disease and measured serum methadone concentrations and simultaneous QTc intervals in a subset of 44 participants. Mean +/- SD QTc increased by 12.4 +/- 23 ms (p <0.001) at 6 months, by 10.7 +/- 30 ms (p <0.001) at 12 months, and the QTc change from baseline to 12 months correlated with the trough (r = 0.37, p = 0.008) and peak (r = 0.32, p = 0.03) serum methadone concentrations.     

Repolarization duration in patients with conduction disturbances after myocardial infarction

This study compared different measurements of repolarization duration in patients after infarction with and without conduction disturbances and evaluated the prognostic significance of repolarization parameters for predicting mortality in patients with conduction abnormalities. The study population consisted of 3,282 patients after recent myocardial infarction. Repolarization duration was measured using Bazett QTc and JTc (QTc minus QRS) and Rautaharju QT and JT(RR) formulas. All-cause mortality was the end point of the predictive models. In 259 patients with conduction disturbances, 76 (2.3%) had indeterminate ventricular conduction disturbances, 126 (3.8%) had right bundle branch block, and 47 (1.4%) had left bundle branch block. Patients with left bundle branch block demonstrated excessive prolongation of the QTc interval, which was not observed when using the JT(RR) interval. There were no significant differences in repolarization duration by gender in patients with conduction abnormalities. Repolarization parameters were uniformly dichotomized at the 75th percentile (QTc interval >490 ms, JTc interval >360 ms, QT(RR,QRS) interval >433 ms, JT(RR) interval >359 ms) to determine their prognostic significance for predicting mortality. After adjustment for significant clinical predictors of mortality, the hazard ratios were 1.65 for QTc interval (p = 0.062), 1.46 for JTc interval (p = 0.168), 1.71 for QT(RR,QRS) interval (p = 0.043), and 1.70 for JT(RR) interval (p = 0.044)(.) In conclusion, patients with left bundle branch block, right bundle branch block, or indeterminate ventricular conduction disturbances show longer repolarization duration than patients without these conduction disturbances, and QT(RR,QRS) and JT(RR) intervals reflect better than QTc repolarization duration in patients with conduction disturbances. QT(RR) and JT(RR) intervals significantly and independently predict mortality in patients after infarction with conduction disturbances.     

QT dispersion in patients with chronic heart failure: beta blockers are associated with a reduction in QT dispersion

OBJECTIVE: To compare QT dispersion in patients with impaired left ventricular systolic function and in matched control patients with normal left ventricular systolic function. DESIGN: A retrospective, case-control study with controls matched 4:1 for age, sex, previous myocardial infarction, and diuretic and beta blocker treatment. SETTING: A regional cardiology centre and a university teaching hospital. PATIENTS: 25 patients with impaired left ventricular systolic function and 100 patients with normal left ventricular systolic function. MAIN OUTCOME MEASURES: QT and QTc dispersion measured by three methods: the difference between maximum and minimum QT and QTc intervals, the standard deviation of QT and QTc intervals, and the "lead adjusted" QT and QTc dispersion. RESULTS: All measures of QT/QTc dispersion were closely interrelated (r values 0.86 to 0.99; all p < 0.001). All measures of QT and QTc dispersion were significantly increased in the patients with impaired left ventricular systolic function v controls (p < 0.001): 71.9 (6.5) (mean (SEM)) v 46.9 (1.7) ms for QT dispersion, and 83.6 (7.6) v 54.3 (2.1) ms(-1-2) for QTc dispersion. All six dispersion parameters were reduced in patients taking beta blockers (p < 0.05), regardless of whether left ventricular function was normal or impaired-by 9.4 (4.6) ms for QT dispersion (p < 0.05) and by 13.8 (6. 5) ms(-1-2) for QTc dispersion (p = 0.01). CONCLUSIONS: QT and QTc dispersion are increased in patients with systolic heart failure in comparison with matched controls, regardless of the method of measurement and independently of possible confounding factors. beta Blockers are associated with a reduction in both QT and QTc dispersion, raising the possibility that a reduction in dispersion of ventricular repolarisation may be an important antiarrhythmic mechanism of beta blockade.     

The relationship between iron stores and corrected QT dispersion in patients undergoing hemodialysis.

OBJECTIVE: Cardiac arrhythmias commonly occur in hemodialysis patients. QT dispersion (QTd=QTmax-QTmin) reflects heterogeneity of cardiac repolarization, and increased QTd is known to predispose the heart to ventricular arrhythmias and sudden cardiac death. The aim of our study was to assess the association of iron stores, reflected by transferrin saturation (TSAT) and ferritin, with the dispersion of corrected QT intervals (QTc) in patients undergoing hemodialysis. METHODS: This cross-sectional, case-controlled study included 40 patients (23 men and 17 women) with renal failure undergoing hemodialysis (Patient group) and 27 subjects (10 men and 17 women) with normal renal function (Control group). In all patients and control subjects, QT intervals were measured on electrocardiogram, and QTc intervals and QTc dispersion were calculated. Electrolyte, hemoglobin and serum TSAT and ferritin levels were also determined. RESULTS: Hemodialysis patients had significantly greater QTc dispersion compared to that of control subjects (61.7+/-23.0 msec vs. 46.0+/-15.7 msec; p=0.001). Though serum iron levels were significantly associated with greater QTc dispersion (r=0.324, p=0.042), other electrolyte levels, duration of dialysis, TSAT and serum ferritin levels were not. CONCLUSION: Although hemodialysis patients have greater QTc dispersion than control subjects, their levels of iron stores as reflected by TSAT and ferritin levels, does not correlate with the degree of QT dispersion.     

Electrophysiologic evaluation of encainide with use of monophasic action potential recording

The electrophysiologic effects of encainide in the intact dog heart were evaluated with the use of monophasic action potential and His bundle recordings. Eight mongrel dogs were given 2.7 mg/kg body weight of encainide in two intravenous infusions. Plasma concentration, blood pressure, surface electrocardiogram, atrial and His bundle electrograms, right atrial and ventricular monophasic action potentials and the right atrial and ventricular effective and functional refractory periods were recorded before and 15 to 45 minutes after each infusion. Basic cycle length and A-H, H-V, QRS and Q-T_C intervals were significantly prolonged after administration of the drug. The refractory periods and the monophasic action potential durations were significantly increased in both the atrium and the ventricle although the increases were more pronounced in the atrium. It is concluded that encainide is a class I antiarrhythmic agent with properties very similar to those of quinidine.     

Cardiac autonomic neuropathy and its correlation with QTc dispersion in type 2 diabetes

This study was conducted on 50 patients of diabetes mellitus type 2 and 20 healthy controls to correlate severity of diabetic cardiac autonomic neuropathy with QTc interval and QTc dispersion. Five standard cardiovascular response tests were carried out (i.e. Valsalva ratio, expiration-inspiration ratio, immediate heart rate response to standing, fall of systolic blood pressure on standing and sustained hand grip test) to determine the severity of cardiac autonomic neuropathy by scoring system. QTc dispersion was determined by subtracting heart rate-corrected minimum QTc interval (QTc min) from maximum QT interval (QTc max) from standard electrocardiogram. Severity of cardiac autonomic neuropathy strongly correlated with QTc dispersion (r = 0.760; p = 0.0001). Correlation of severity of cardiac autonomic neuropathy with QTc max and QTc mean was also found but weaker than with QTc dispersion (r = 0.663, r = 0.542, p = 0.0001 each) and no correlation was found with QTc min (r = 0.177; p = 0.17). This shows that QTc dispersion is a better predictor of cardiac autonomic neuropathy than any of above three QTc intervals. QTc max, QTc mean and QTc dispersion were significantly higher (p < 0.001) in diabetics with autonomic neuropathy (450 +/- 23, 423 +/- 22 and 57 +/- 12 msec; n = 30) than without neuropathy (407 +/- 14, 397 +/- 15 and 20 +/- 7 msec; n = 20) and control subjects (408 +/- 20, 399 +/- 19 and 19 +/- 7 msec; n = 20) but QTc min remained same in the three groups (393 +/- 21, 387 +/- 12, 388 +/- 19 msec, respectively) (p > 0.05). Correlation of QTc dispersion was stronger with QTc max (r = 0.781; p < 0.001) than QTc mean (r = 0.625; p = 0.001) but not with QTc min (r = 0.097; p = 1.0) which suggests that regional increase in QT interval due to regional autonomic denervation leads to increased QTc dispersion. Thus, QTc dispersion is a sensitive, non-invasive, simple and cost-effective predictor of cardiac dysautonomia.     

Electrophysiological effects of intravenous sotalol. Relation with plasma levels

The object of this study was to confirm the electrophysiological effects of sotalol, a betablocker which increases the duration of the action potentials of myocardial cells, and to investigate the relationship of these effects with the doses used and plasma concentrations (PC) of the drug. 13 patients (23 to 72 years) were divided into 3 groups: Group 1 (n = 5): 0.6 mg/kg; Group 2 (n = 4): 1.2 mg/kg; and Group 3 (n = 5): 1.8 mg/kg. Measurements were performed before and 35 minutes after starting a 15 minute intravenous infusion of sotalol. At all doses, sotalol decreased the heart rate (HR), increased the corrected sinus node recovery time (CSNRT), prolonged the effective refractory periods (ERPA) and functional refractory periods (FRPA) of the right atrium. Atrioventricular conduction was depressed; prolongation of AH at an imposed rate of 100/min, prolongation of the nodal refractory periods (ERPN and FRPN), and an earlier Wenckebach point. The corrected QT interval (QTc) and ventricular refractory period (ERPV) increased. The QRS complexes and HV intervals were unchanged. Increases of CSNRT, AH, ERPN, FRPN, QTc, and ERPV were observed after the first dose (Group 1). At the dose of 1.8 mg/kg (Group 3) all parameters were modified (except the QRS and HV). All patients increased their ERPV by more than 20 p. 100. The parameters which illustrated the dose-effect relationship were the HR, ERPA, FRPN, and CSNRT. The PC of sotalol measured 60 minutes after starting the infusion were 0.58 +/- 0.23 microgram/ml (Group 1), 0.78 +/- 0.32 microgram/ml (Group 2) and 1.73 +/- 0.43 microgram/ml (Group 3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of the class III antiarrhythmic drug, d-sotalol, in patients with congestive heart failure

In contrast to Vaughan Williams class I drugs, class III drugs, such as d-sotalol, may not be negative inotropic. These drugs block potassium ion channels and prolong repolarization, theoretically leading to improved contractility. We investigated the hemodynamic actions of acute intravenous administration of 1.5 mg/kg of d-sotalol in 28 patients with congestive heart failure randomized to receive placebo (n = 10) or active drug (n = 18) in a double-blind study. A Swan-Ganz catheter was placed in all patients ≥16 hours before drug administration. All hemodynamic variables were assessed at baseline and 30 minutes and 1, 2, 4, 8, and 12 hours after administration of the drug. Electrocardiograms were obtained before and 1, 2, 4, and 12 hours after drug administration. The QT interval increased from 370 ± 9 to 426 ± 14 ms at 1 hour, whereas the QTc increased from 433 ± 5 to 470 ± 12 ms (both p < 0.001). The increase was still statistically significant at 12 hours. There was no change in the placebo group. Although heart rate decreased in the d-sotalol group (84 ± 2 to 76 ± 2 at 1 hour, p < 0.001), there were no changes in blood pressure or right atrial pressure. Cardiac index decreased slightly (2.0 ± 0.2 to 1.9 ± 0.1 mm Hg), consistent with the lower heart rate. Pulmonary capillary wedge pressure decreased from 18.9 ± 2.4 to 17.9 ± 1.9 mm Hg at 1 hour despite reduced cardiac index. We conclude that in contrast to class I, II, and IV antiarrhythmic drugs, d-sotalol exerts no clinically important acute hemodynamic actions at doses that produce electrophysiologic effects.     

Evaluation of a 12-lead digital Holter system for 24-hour QT interval assessment

BACKGROUND: Drug induced QT prolongation may precipitate life threatening cardiac arrhythmias. Evaluation of the QT prolonging effect of new pharmaceutical agents in a 'thorough QT/QTc study' is being mandated by FDA. The purpose of this study was to evaluate an automated 12-lead digital Holter system for a thorough QT/QTc study. METHODS: Five healthy volunteers underwent 24-hour digital Holter monitoring. Each recording underwent a fully automated QT analysis (AQA) followed by an onscreen complete manual over read (MOR). Each recording was analyzed twice at least 2 weeks apart. The effect of data sampling (5-min segment/hour), the system sensitivity to detect 5-ms increase in QT, and the ability to assess circadian variation were evaluated. RESULTS: The AQA resulted in identical QT for the first and second analyses, but with obvious errors in QT measurements. Compared to the complete onscreen MOR, the mean QT was longer with AQA (416 +/- 41 vs. 387 +/- 30 ms, p < 0.001), correlation; r = 0.3. The reproducibility of AQA with complete MOR was very good (QT: 387 +/- 30 vs. 387 +/- 30 ms, coefficient of variation: 0.2%, r = 0.986. The 5-min mean QT intervals correlated well with the hourly mean QT intervals (r = 0.994, p < 0.001, coefficient of variation = 1 ms) and both showed a similar circadian variation. The system was sensitive to detect a 5-ms change in QT intervals (5 +/- 2 ms, coefficient of variation = 0.6%, r = 0.998, p < 0.001). CONCLUSIONS: The AQA is not an acceptable method, while the automatic analysis with complete MOR is a highly sensitive and reproducible method. Data sampling by analyzing 5-min segments per hour is sensitive and reproducible.     

QT dispersion and hypertensive heart disease in the elderly

AIM: To determine the predictors and risk of increased QT dispersion in the elderly hypertensive patients. METHODS: A 12-lead electrocardiogram (ECG), M-mode echocardiography and ambulatory blood pressure as well as Holter monitoring were performed for 67 patients over 60 years of age with essential hypertension (I and II(o) WHO). The presence of ischaemic changes on ECG was evaluated based on the Minnesota Code. QT intervals were corrected with Bazett's formulae and QT dispersion was determined as the difference between maximal and minimal QTc intervals. Interventricular septal thickness (IVSTd), left ventricular internal diameter (LVDd) and posterior wall thickness (PWTd) were measured and left ventricular mass index (LVMI) was calculated. Subjects were divided according to the median of QTc dispersion (0.10 s). The differences between groups were assessed using chi-squared and Student's t-test. RESULTS: Subjects with increased QTc dispersion did not differ from those with low QTc dispersion when age, gender and body mass index were analysed. Similarly, the average systolic blood pressure, diastolic blood pressure and blood pressure variability were comparable in both groups. The mean QTc interval was similar in both groups. In patients with increased QT dispersion, left ventricular hypertrophy (LVH) and ischaemic changes on ECG were more frequently recognized (respectively 41.2 versus 18.2%, P < 0.001; 47.1 versus 21.2%, P < 0.05). Moreover, these subjects presented a significantly greater number of premature ventricular beats (317.1 +/- 665.6 versus 64.88 +/- 188.6, P < 0.05) and higher classes of Lown's arrhythmia scale (classes III-IV, 23.35% versus 9.1%). LVMI was insignificantly higher in the group with greater QTc dispersion (165.82 +/- 54.5 versus 145.07 +/- 36.47 g/ m2). Other echocardiographic indices of LVH were similar in both groups. On the other hand, the analysis of regression indicated positive correlation between the dispersion of QTc interval and thickness of left ventricle walls (for IVSd - r = 0.37; for PWd - r = 0.31), relative wall thickness (r = 0.28) and LVMI (r = 0.28). CONCLUSIONS: QTc dispersion is increased in the elderly hypertensive individuals, with the presence of LVH and myocardial ischaemia on ECG. These patients are more likely to demonstrate severe ventricular dysrhythmias.     

Assessment of QT dispersion in symptomatic patients with congenital long QT syndromes.

It has been suggested that QT dispersion recorded on the surface electrocardiogram may be a predictor of arrhythmic events in patients with congenital QT prolongation. To evaluate this, 9 patients (6 female, mean age 17.6 years) with congenital long QT syndromes, all of whom had syncope and documented torsades de pointes, were studied. Patients were studied off treatment and during therapy with beta-blocking agents. Three patients were also studied after left stellate ganglionectomy. An age-matched control group was also studied. Good quality 12-lead electrocardiograms were recorded from all patients. For each lead, QT and RR intervals were measured, and QTc value was calculated. QT and QTc dispersions were calculated for each patient. Patients had a significantly longer mean QT interval compared with that of the control group (450 +/- 100 vs 359 +/- 63 ms; p = 0.015) at similar mean RR intervals (736 +/- 231 vs 783 +/- 289 ms), with a longer mean QTc value (0.53 +/- 0.08 vs 0.41 +/- 0.02 s1/2; p = 0.004). Patients also had longer QT and QTc dispersions compared with those of the control group (110 +/- 45 vs 43 +/- 12 ms [p = 0.004], and 0.108 +/- 0.03 vs 0.05 +/- 0.02 s1/2 [p = 0.002], respectively). QT and QTc dispersions on and off beta-blocking agents were not significantly different. Comparing patients with frequent and those with infrequent symptoms, there was no difference in QT or QTc dispersion either off treatment or during therapy with beta-blocking agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

盐酸关附甲素在五指山小型猪急性缺血模型中的电生理学作用

目的研究分析盐酸关附甲素（AHH）对结扎冠状动脉（冠脉）造成急性缺血的五指山小型猪的心电图及心内电生理指标影响。方法选用五指山小型猪,随机分为A组（结扎冠脉并应用AHH）、B组（不结扎冠脉仅应用AHH）、C组（结扎冠脉而应用生理盐水）三组,分别记录急性缺血（或对照）动物用药前后心房、房室交界区、心室电图及体表监测导联心电图。结果共收集五指山小型猪有效实验资料每组各9只,性别、月龄、身长、体重等基线资料组间差异无统计学意义。在急性缺血模型中与生理盐水比较,AHH延长P波及PR间期,缩短QTc间期,并延长心房不应期及室房逆传,缩短心室不应期。与非缺血模型比较,应用AHH在急性缺血模型中出现QT及QTc间期缩短,心室相对不应期及功能不应期缩短,室房逆传有效不应期延长。实验过程中,无论急性缺血或非缺血模型,应用AHH均未发现新的心律失常。结论初步动物实验结果证实,在急性缺血模型中,AHH表现出一定的电生理作用而未引发新的心律失常。