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J Weissenburger

Publications and source records attributed to J Weissenburger.

At least 37 records · Page 2Linked to original sources
PubMed1993

Experimental models of torsades de pointes.

Torsades de pointes is the most typical ventricular tachycardia involving QT-interval prolongation. It is a rather unusual but potentially lethal ventricular tachycardia with a distinctive morphology favored by bradycardia, antiarrhythmic drugs and hypokalemia and requires specific treatment. Torsades de pointes has been shown to be related to bradycardia-dependent early afterdepolarizations (EAD) and/or increased dispersion of repolarization. However, although EAD can be obtained relatively easily in vitro with quinidine or sotalol, torsades de pointes are very difficult to reproduce in animal models. The models of torsades de pointes which have been proposed can be categorized as morphological, EAD-related or pharmacological models. The purpose of the 'morphological' models was to reproduce the twisting of QRS axis typical of torsades de pointes, with no consideration of other aspects such as long QT or bradycardia. These models were produced by epicardial electrical or chemical (aconitine) stimulation at two distant ventricular sites or by overdosing of quinidine in dogs with acute myocardial infarction. The second type of model focused on the conditions producing EAD in vitro. Ventricular tachycardias were obtained in anesthetized dogs using toxics such as cesium or anthopleurine, both producing EAD in vitro. These ventricular tachycardias were shown to be sensitive to magnesium, heart rate and autonomic tone, but torsades de pointes remained rare, at least after cesium injections. The pharmacological models that could be used to study the QT-dependent proarrhythmic effects of drugs are the anesthetized rabbit with alpha-adrenergic stimulation, and the conscious dog model with chronic AV-block and diuretic-induced hypokalemia. Methoxamine-treated anesthetized rabbits develop ventricular tachycardias during clofilium infusions. These ventricular tachycardias, although appearing at very high heart rates, have typical torsades de pointes aspects and are often associated with giant QT waves. The specificity of the model remains to be tested. In our conscious bradycardic and hypokalemic dogs, quinidine and sotalol but not flecainide, propranolol or lidocaine induced QT-dependent arrhythmogenic effects and torsades de pointes. Efficacy of high rate stimulations and magnesium were repeatedly observed. This demanding model, especially designed for qualitative drug comparisons, is also well suited to studies on the mechanisms of initiation of torsades de pointes. The pertinence of these models for estimating the risk of QT-dependent proarrhythmias associated with non-antiarrhythmic agents remains to be tested.

Animals↗
PubMed1993

Antiarrhythmic effect of a sotalol-mexiletine combination on induced ventricular tachycardia in dogs.

Mexiletine was recently shown to antagonize the effects of sotalol on repolarization of canine Purkinje fibers. The significance of this interaction for the antiarrhythmic properties of these drugs remains unknown. The antiarrhythmic effects of sotalol and mexiletine alone and in combination on induced ventricular tachycardias (VTs) were assessed in 20 conscious dogs with chronic infarction. Electrophysiological measurements and programmed stimulation were performed before and after the infusion of sotalol (4 mg/kg) or mexiletine (4 mg/kg), and after infusion of the combination. The electrophysiological parameters didn't change after mexiletine. Sotalol alone and the combination both similarly prolonged the QT interval and VERP. Induction of VT by programmed stimulation was not prevented by mexiletine, but the cycle length of monomorphic VT was increased in 7 of 10 dogs. The induction of VT was prevented by sotalol (11/16 dogs), but VTs were not slowed significantly. Sotalol plus mexiletine prevented VT as did sotalol alone (11/16 dogs). The combination also increased the cycle length of VT in all eight dogs with monomorphic VT. Thus, the antagonism shown in vitro appears to have no consequences in this model. On the contrary, the sotalol-mexiletine combination showed some additive antiarrhythmic effects on induced VT in dogs.

Animals↗
PubMed1992

[Experimental models of torsades de pointes].

Several experimental models of torsades de pointes have been proposed these last years. They can be classified in 2 categories: morphological models designed to reproduce the ECG features of "torsade", with in vivo ventricular stimulations or with computer ECG stimulations and pharmacological models designed to obtain in vivo early after depolarizations, with toxic agents such as cesium chloride and anthopleurine, or with commercialized or new pharmaceutical drugs. These models improved electrophysiologic and pharmacologic knowledge of torsades de pointes. The respective roles of early after depolarizations in torsades initiation and of reentry in the following beats of the salvos is now recognized. Induction protocols were described, which appeared to involve an inotropic potentiation following burst or repetitive extrastimuli. A more accurate evaluation of arrhythmogenic risk associated with new drugs could be developed.

Animals↗
PubMed1991

Methods and limitations of an experimental model of long QT syndrome.

An experimental model of the long QT syndrome has been developed in conscious dogs. This report discusses the methods used in its preparation and the strengths and weaknesses of the model. This new model is suitable for screening the bradycardia-dependent proarrhythmic effects of drugs and for studying the electrophysiology of "torsades de pointes." Permanent bradycardia (RR: 1558 +/- 83 ms) was obtained in 37 dogs by chemically-induced complete atrioventricular block. A 10% further increase of ventricular repolarization (QT: 306 +/- 7.0 ms to 331 +/- 5.5 ms) was obtained in 28 of these dogs by diuretic-induced hypokalemia. Diuretics, despite saline replacement, induced some degree of functional renal failure and extracellular volume losses. The QT interval increased although ventricular cycle length decreased slightly. These biological and electrophysiological parameters were reproducible except for a slow increase in plasma creatinine. Cardiac failure and sudden death rarely occurred. The most severe, but reversible, renal failure occurred in some dogs given the highest diuretic doses. Hypokalemia resulted in ventricular arrhythmias in only 6 dogs, 2 of them exhibiting runs of ventricular tachycardia and even "torsade de pointes" as their potassium levels fell below 2 mmol/L. The results of studies with several drugs using the model, with or without hypokalemia, or with bradycardia worsened by propranolol are analysed.

Animals↗
PubMed1991

Arrhythmogenic activities of antiarrhythmic drugs in conscious hypokalemic dogs with atrioventricular block: comparison between quinidine, lidocaine, flecainide, propranolol and sotalol.

In order to create and evaluate a model sensitive to QT-dependent proarrhythmic effects of drugs, a long QT syndrome was produced in chronically instrumented dogs with bradycardia and hypokalemia. Bradycardia (mean cycle length: 1495 +/- 78 msec) was provided by permanent atrioventricular block and hypokalemia (K+ = 2.6 +/- 0.05 mmol/l) by high doses of diuretics. To evaluate that model, six of these conscious dogs were subjected to quinidine, flecainide, lidocaine, propranolol and sotalol infusions. In crossover design, drugs were infused i.v. at rates allowing stable and nontoxic drug plasma levels during the experiment. Four-lead ECGs were recorded for arrhythmias for 30 min before (base line) and 75 min after onset of infusion. Ventricular cycle length was increased dramatically by sotalol, lidocaine and propranolol (+618 +/- 192, +388 +/- 125 and +329 +/- 114 msec, respectively) and QT interval was increased by sotalol, quinidine and flecainide (+56 +/- 8, +31 +/- 7.9 and +20 +/- 5.7 msec, respectively). Quinidine and sotalol, but not flecainide, propranolol or lidocaine, exhibited significant arrhythmogenic activities. During quinidine infusion, most dogs exhibited some ventricular arrhythmias whose most severe forms were runs of ventricular tachycardia. These arrhythmias were suppressed by pacing at high rates. During sotalol infusion, five out of six dogs exhibited typical "torsades de pointes." This incidence was not related to the slowing effects of sotalol on idioventricular pacemakers, because a similar incidence was obtained in five complementary dogs paced at 40 bpm. It could be related to dose, because torsades de pointes occurred only once in another group of five dogs receiving half the dose used in the controlled study. Only quinidine and sotalol, but not propranolol, flecainide or lidocaine, are clinically associated to torsades de pointes. They were also the only drugs associated with proarrhythmic events in the present study, a fact suggesting that QT-dependent arrhythmogenic effects of drugs can be reliably evaluated in conscious hypokalemic dogs with complete atrioventricular block.

Animals↗
PubMed1990

Comparison of the cardiac electrophysiological effects of flecainide and hydroquinidine in anesthetized dog: concentration-response relationship.

The concentration-dependent effects of flecainide and hydroquinidine were studied in closed-chest anesthetized dogs. The electrophysiological effects of three doses (i.v. infusions followed by an appropriate perfusion to plateau the plasma levels) of flecainide (1, 2, and 3.9 mg/kg) and hydroquinidine (2, 4, 7.5 mg/kg) were tested. Sinus cycle length, QRS duration, His-Purkinje and AV nodal conduction times, Wenckebach period, atrial, nodal, and ventricular refractory periods, and corrected QT interval were measured before and 30 min after the beginning of each bolus infusion. Both hydroquinidine and flecainide increased the sinus cycle length, and slowed cardiac conduction to different degrees. Hydroquinidine and flecainide prolonged ventricular conduction; flecainide had a greater effect at the His-Purkinje level. Hydroquinidine exhibited only a weak and nonsignificant effect at the AV node, whereas flecainide dramatically prolonged conduction and refractoriness. The two drugs increased AERP equally. The QT interval and ventricular refractoriness were similarly prolonged to the same extent by both drugs (32 and 35% after the third doses of hydroquinidine and flecainide, respectively). The high plasma flecainide levels reached in our study (1.47 and 2.9 micrograms/ml after the second and third doses, respectively) may explain these effects, which are unexpected for a class Ic agent. These results suggest that flecainide could increase the QT interval, like a class Ia drug when its plasma level exceeds the therapeutic range.

Anesthesia↗
PubMed1989

Reduced REM latency predicts response to tricyclic medication in depressed outpatients.

Forty-two outpatients with major depressive disorder entered a double-blind, randomized trial of either desipramine or amitriptyline for a minimum of 6 weeks. Pretreatment polysomnographic and clinical measures were used to predict response. Response was defined as a 17-item Hamilton Rating Scale for Depression score less than or equal to 9 at the end of treatment. There was a 61.1% response rate for patients treated with amitriptyline and a 66.7% response rate for patients treated with desipramine. Reduced REM latency (2-night mean less than or equal to 65.0 min) predicted a positive response to these tricyclic antidepressants. REM latency did not differentiate between desipramine or amitriptyline responders. More patients with reduced REM latency (80%) responded to treatment compared with patients with nonreduced REM latency (50%). The 80% response rate in reduced REM latency depressed patients confirms our previous findings in a mixed inpatient and outpatient sample. Contrary to our hypothesis, in this sample, endogenous depression was not associated with a good response to tricyclic medication.

Adolescent↗
PubMed1989

Comparative hemodynamic study of a new aminosteroid: LND-623 with its 20 alpha-isomer: LND-369, and with digoxin and digoxigenin-rhamnoside in the anesthetized dog.

Hemodynamic effects of LND-623, a new aminosteroid lacking the C17 lactone ring and the C14 hydroxyl group common to the natural glycosides, were studied in the pentobarbital-anesthetized dog and compared to those of its 20 alpha-isomer LND-369 and of digoxin and digoxigenin-rhamnoside (DRh). Twenty-four mongrel dogs were divided into 4 groups. Group I received either LND-623 or saline on study day 1 and the other drug or saline 1 wk later. Saline was replaced by digoxin in group II, digoxigenin-rhamnoside in group III, and LND-369 in group IV. All drugs except LND-369 were infused as 3.10(-9) mol.kg-1.min-1 over 20 minutes. LND-369 was infused at twice the dose. LND-623 increased left ventricular dP/dt for at least 3 h with a peak at end-infusion or 15 min later, accompanied by a transient vasopressor effect. LND-369 induced, at twice the dose, an inotropic effect of comparable magnitude but of shorter duration. Inversely, it provoked a more marked and prolonged vasopressor effect than its 20 beta-isomer, LND-623. Maximal digoxin inotropic effect occurred later but was of comparable magnitude to that induced by LND-623. Its vasopressor effects reached a plateau rapidly and remained sustained until min 200. Digoxigenin-rhamnoside inotropic but not vasopressor effects are weaker than those of LND-623. It is concluded that LND-623, although lacking the most common structural features of the natural cardiac glycosides, provoked rapid and sustained inotropic activities with transient vasopressor effects. These time-course effects differ from digoxin, and these differences are unrelated to their sugar-moiety characteristics. LND-623 inotropic effect is twice as potent as its 20 alpha-isomer.

Anesthesia↗
PubMed1989

[Electrophysiologic effects of intravenous 3-hydroxy-dihydroquinidine (LNC-834) in man].

The object of this study was to determine the electrophysiological effects of 3-hydroxy-dihydroquinidine (3-OH-HQ) in man. The electrophysiological parameters were measured in 12 patients before and after intravenous infusion of 5 mg/kg of 3-OH-HQ in 15 minutes. The mean plasma concentrations obtained varied from 2.4 +/- 1.1 mg/l at the 20th minute to 0.9 +/- 0.3 mg/l at the 60th minute. In these concentrations, 3-OH-HQ did not cause hypotension or affect the heart rate and nodal conduction. It did, however, prolong infra-hisian and intraventricular conduction and ventricular repolarisation from the 20th to the 60th minute after starting the infusion. The peak effect was observed at the 20th minute (+19 +/- 3.4 ms; +14.6 +/- 3.5 ms; and +44.5 +/- 6.6 ms, respectively). The 3-OH-HQ increased the effective atrial and ventricular refractory periods at the 30th minute (+21.8 +/- 5.5 ms and +22.3 +/- 7 ms, respectively). However, the ventricular effect only was discernable at the 60th minute. These effects are quantitatively comparable to those of quinidine. Extrapolation of these results to the effects of chronic oral treatment should be reserved as the therapeutic zone of this new molecule has not yet been determined.

Aged↗
PubMed1988

Comparison between clinician-rated and self-reported depressive symptoms in Italian psychiatric patients.

The Inventory for Depressive Symptomatology is a new scale for measuring depressive symptoms. The reliability, validity and correlations between self-report and clinician-rated versions of the scale were examined in 86 Italian psychiatric patients. Results confirmed the validity and internal consistency of the scales. Self-ratings and clinician ratings were highly correlated. Total score on the self-rating scale was generally higher than the corresponding clinician scale score. Item analysis revealed that most items were rated slightly higher by self-report, with the items contributing most to this discrepancy being psychomotor agitation and retardation, self-outlook, and irritable mood. Both quality of mood and psychomotor agitation were more frequently endorsed by self-report than by clinician rating.

Adult↗
PubMed1988

Fluoxetine versus trazodone in the treatment of outpatients with major depression.

Fluoxetine and trazodone were compared in a double-blind, randomized, parallel, 6-week trial in 43 outpatients with major depression after a 1-week single-blind placebo period. Thirty-five patients completed at least 3 weeks of active medication, while 25 patients completed all 6 weeks. Response rates, whether defined by end-of-treatment Hamilton Rating Scale for Depression (HAM-D) score less than 10 or by a 50% reduction in HAM-D scores, were equivalent for the two medications. For fluoxetine, HAM-D scores were significantly lower at Weeks 1 and 2 compared with those of trazodone. Trazodone improved sleep significantly more than fluoxetine. Fluoxetine was associated more frequently with weight loss (p = .002) and less frequently with dizziness (p = .04) than trazodone.

Ambulatory Care↗
PubMed1988

Dexamethasone suppression test status does not predict differential response to nortriptyline versus amitriptyline.

Thirty-five (35) inpatients with nonpsychotic major depression were randomly assigned to either amitriptyline or nortriptyline on a double-blind basis, following a 4- to 10-day placebo run-in period. Thirty-two patients completed at least 3 weeks of active medication. The 1.0-mg dexamethasone suppression test (DST) was performed before treatment. Twelve of 32 patients were DST nonsuppressors. Both medications were equally effective. Pretreatment DST status failed to predict overall response to both medications combined. DST status also did not predict differential medication response. These data argue, along with several other studies, that pretreatment DST status may be of limited value in selecting a particular tricyclic antidepressant compound.

Adult↗
PubMed1988

[Sotalol-induced torsades de pointe in the conscious dog with atrioventricular block. Role of hypokalemia].

Sotalol is a beta-blocking agent endowed with class III electrophysiological properties. It has proved clinically effective in the treatment of arrhythmia, but episodes of torsades de pointe have been observed, particularly (though not exclusively) in the presence of hypokalaemia. The effect of sotalol with or without hypokalaemia was studied on a recently developed model for experimental torsades de pointe. Conscious dogs with complete atrioventricular block (ventricular cycle RR = 1530 +/- 170 ms) and provided with permanent atrial and ventricular epicardial electrodes were given sotalol intravenously either as a 4.5 mg/kg bolus injection or as a 1.5 mg/kg/h infusion. Group I dogs (n = 8) had normal blood potassium levels (4.3 +/- 0.1 mEq/1); following sotalol (plasma concentration 3.7 +/- 0.2 micrograms/ml) the ventricular rhythm was electrically driven to 25/min (RR = 240 ms) and QT was increased by 68 +/- 11 ms; torsades de pointe occurred in 5/8 animals (62 p. 100). Group II dogs (n = 6) had diuretic-induced hypokalaemia (2.6 +/- 0.1 mEq/1); following sotalol (plasma concentrations 3.8 +/- 0.3 micrograms/ml) the ventricular rhythm also depended on an external pacemaker to reach 25/min (in all but 1 dog) and QT increased by 46 +/- 11 ms; torsades de pointes were obtained in 5/6 animals (83 p. 100). These torsades de pointe were prevented in every case by rapid ventricular pacing (100-120/min). Thus, the pro-arrhythmic effects of sotalol were very frequent on this experimental model, but hypokalaemia was not necessary for torsades de pointe to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Depression and dexamethasone suppression testing in children and adolescents.

The authors compare the incidence of dexamethasone nonsuppression in a large group of child and adolescent inpatients (N = 94) diagnosed by two criteria (DSM-III and Weinberg criteria). The incidence of dexamethasone suppression test nonsuppression in patients diagnosed with DSM-III major depressive disorder (n = 33) was 55%, compared to 11% in those with no affective disorder (n = 35). This was compared to the incidence of dexamethasone suppression test nonsuppression utilizing Weinberg criteria. In addition, symptoms that to varying degrees discriminated suppressors from nonsuppressors were examined. These included change in school performance and, to a lesser degree, somatic complaints and weight and appetite changes. Differences in the diagnostic criteria are discussed.

Adolescent↗
PubMed1987

[Study of sinus function and nodal conduction using transesophageal recordings].

Transoesophageal pacing is mainly used for treatment of supraventricular tachycardias and assessment of refractory periods of accessory pathways. It has been proposed for the study of sinus node function and A-V nodal conduction. The aim of this study was to know if transoesophageal pacing could modify the vago-sympathetic tone, therefore the results of the tests, knowing it can be discomfortable and that endodigestive procedures can induce vagal responses. Furthermore, the stimulation is elicited near the left atrium, and not in the right atrium as during endocavitary tests. We have compared in 20 patients (age 68 +/- 12) the results obtained by both endocavitary and transoesophageal pacing (tension 21.2 +/- 4.5 V, duration 16 msec, interelectrode spacing 30 mm). We measured sino-atrial conduction time (SACT), sinus node recovery time (SNRT), Wenckebach's point and nodal refractory periods. After introduction of the oesophageal lead we observed a significant (p less than 0.01) but slight and transitory tachycardia. The results of A-V nodal conduction parameters were not significantly different and were significantly correlated (r = 0.94 for Wenckebach's point and effective refractory period). For the sinus node function, there was no significant difference between the parameters if the oesophago-atrial delay (mean 104.4 +/- 25.9 msec) is taken into account. The correlation is poor for sino-atrial conduction time (corrected SACT, r = 0.55), tighter for sinus node recovery time (maximal corrected SNRT, r = 0.92).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The Inventory for Depressive Symptomatology (IDS): preliminary findings.

The Inventory for Depressive Symptomatology (IDS) is a new measure of depressive signs and symptoms. Both self-report and clinician-rated versions are under development. The IDS-SR (self-report) was completed by 289 patients, 285 of whom were outpatients. Unipolar major depression (n = 174), bipolar disorder (n = 44), euthymic (S/P unipolar or bipolar) depression (n = 33), and other psychiatric disorders (n = 38) were included. The IDS-SR had good internal reliability (coefficient alpha = 0.85), and significantly correlated with both the Hamilton Rating Scale for Depression (HRSD) (r = 0.67) and the Beck Depression Inventory (BDI) (r = 0.78). The clinician-rated IDS (IDS-C) was administered to 82 outpatients (75 with unipolar or bipolar disorder, 5 with other psychiatric disorders, and 2 euthymic (S/P unipolar) depressions). Coefficient alpha (0.88) suggested strong internal consistency. The IDS-C correlated highly with both the HRSD (r = 0.92) and the BDI (r = 0.61). Discriminant and factor analyses provided evidence for construct validity for both the IDS-C and IDS-SR. Both scales significantly differentiated endogenous from nonendogenous depression defined by Research Diagnostic Criteria (RDC). Factor structures for the IDS-SR revealed four factors: mood/cognition, anxiety, selected endogenous symptoms, and hyperphagia-hypersomnia. The IDS appears applicable to both inpatients and outpatients with endogenous, atypical, and nonendogenous major depression, and may have utility with dysthymics.

Adult↗
PubMed1986

Weight change in depression.

This report describes the weight changes of 109 outpatients during the course of a depressive illness and relates these changes to several potential predictors: age, gender, diagnosis, and scores on the Hamilton Rating Scale for Depression (HRSD), the Beck Depression Inventory, and the three factors on the Eating Questionnaire. Weight changes ranged from -33 to +50 pounds, with 40% of the patients reporting weight gain, 30% weight loss, and 30% no change in weight. Weight loss occurred more rapidly than did weight gain. The disinhibition factor of the Eating Questionnaire was significantly correlated with weight change during depression and, on a stepwise discriminant function analysis, differentiated weight-gaining from weight-losing patients at a high level of statistical significance. Severity of depression also differentiated weight-gaining from weight-losing patients in the discriminant function analysis, but only on the HRSD and at a level of more modest statistical significance.

Adult↗