Search PubMed⌕ Search

Biomedical subjects

P Dorian

Publications and source records attributed to P Dorian.

At least 55 records · Page 3Linked to original sources
PubMed1998

Autonomic correlates of antidepressant treatment using heart-rate variability analysis.

OBJECTIVE: To assess the 24-hour temporal-domain heart-rate variability correlates of treatment with fluoxetine or doxepin for depression. METHOD: A randomized evaluation of fluoxetine and doxepin measured a 50% change in the Hamilton Depression Rating Scale (HDRS) score as a response to therapy and was correlated with measures of standard deviation of the mean of all 5-minute segments of normal electrocardiographic R-R intervals (SDANN), standard deviation of all normal R-R intervals (SDNN), root mean square of successive differences in R-R intervals (r-MSSD), and percentage difference between adjacent normal R-R intervals that are greater than 50 msec (pNN50) from 24-hour electrocardiogram (ECG) tapes. RESULTS: Ten out of 14 patients responded. Response was associated with an increase in SDANN of 17% (P < 0.05). Nonresponse was associated with a 17% decrease in SDANN and a 22% decrease in SDNN (both P < 0.05). No other measures correlated with therapeutic response. No heart-rate variability (HRV) differences between the 2 drug therapies were observed. CONCLUSION: Twenty-four-hour HRV measures may be useful in assessing response to antidepressant therapy.

Analysis of Variance↗
PubMed1998

Effectiveness of fluoxetine and doxepin in treatment of melancholia in depressed patients.

It has been suggested that serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressants (TCAs) in treatment of melancholic depression. We treated 36 depressed ambulatory patients with doxepin or fluoxetine in a double-blind, randomized 6-week trial with placebo run-in. Seven patients treated with doxepin and 13 patients treated with fluoxetine met diagnostic criteria for melancholic depression. Average daily dose was 169.4 +/- 41.6 mg for doxepin and 36.8 +/- 18 mg for fluoxetine. We observed a 50% response rate in both treatment groups, using as outcome criterion reduction of Hamilton Depression Scale Score to less than 10. Regardless of how strict the definition of response, we found fluoxetine to be as effective as doxepin in our group of melancholic outpatients.

Adult↗
PubMed1998

Implantable defibrillators and/or amiodarone: alternatives or complementary therapies.

Many patients with an implanted cardioverter defibrillator (ICD) also receive antiarrhythmic drug therapy. Although an expanding number of patients are receiving ICD therapy, many will not have received previous antiarrhythmic treatment. For patients with an ICD, infrequent arrhythmias and a low probability of inappropriate device discharges, no antiarrhythmic therapy is required. However, for those patients who require an antiarrhythmic drug, amiodarone is a reasonable first choice because of safety in patients with poor LV function. It may be particularly useful for patients with high density ventricular arrhythmias. However, the interactions between ICDs and antiarrhythmic therapy requires close monitoring in order that patient benefit can be optimised, and this review focuses on those interactions.

Aged↗
PubMed1997

A population-based method for the estimation of defibrillation energy requirements in humans. Assessment of time-dependent effects with a transvenous defibrillation system.

BACKGROUND: A weighted logistic regression analysis was developed to allow pooling of patient data for the study of the stability of defibrillation energy requirements with a new nonthoracotomy lead defibrillation system. METHODS AND RESULTS: One hundred twenty patients were prospectively studied with a single-model nonthoracotomy implantable cardioverter defibrillator (ICD) system at the time of implant and at 3 months. The pooled data of all shocks delivered to all patients were fitted to a logistic function to construct a defibrillation voltage/energy dose-response relationship. The crude logit curve was weighted in quartiles according to the average shock energy delivered per patient. Shocks at implant (n = 802; 6.6 +/- 2.5 shocks/patient) and follow-up (n = 292; 2.4 +/- 1.2 shocks/patient) were analyzed. The modeled voltage/energy required for 50% successful defibrillation (95% CI) in the pooled data was 367 V (273, 461) and 9.8 J (6.7, 12.9) at implant and 338 V (264, 412) and 10.5 J (8, 13.0) at follow-up. The conventional measure of lowest successful voltage/energy (95% CI) was 430 V (411, 449) and 12.1 J (11, 13.2) at implant and 415 V (391, 439) and 11.3 J (10, 12.6) at follow-up. There were no statistically significant differences between implant and follow-up energy requirements with either method. CONCLUSIONS: The nonthoracotomy lead system used in this study demonstrated stability of defibrillation energy requirements at implant and 3-month follow-up. A new technique for the estimation of the defibrillation energy dose-response relationship was derived by using a weighted logistic regression analysis.

Aged↗
PubMed1997

Circadian variation of sustained ventricular tachycardia in patients subject to standard adrenergic blockade.

Morning peaks in the circadian variation of sustained ventricular tachycardia (VT) may reflect the contribution of sympathetic activation to onset of VT. We hypothesized that adrenergic blockade would eliminate this morning peak. Fifty-four patients using a defibrillator had 1114 time-stamped episodes of VT requiring therapy with a device: 1012 episodes with and 102 episodes without antiadrenergic medications. Nine patients had episodes both with and without antiadrenergic medication and were examined separately. In patients taking antiadrenergic agents, data fitted to a harmonic regression model revealed a morning peak at 9:00 AM (R2= 0.542; p < 0.05), with a secondary peak at 4 PM. Those not receiving antiadrenergic therapy had a similar morning peak. Antiadrenergic agents as used in standard clinical practice do not prevent circadian variation in onset of VT. This variation may be mediated by systems other than adrenergic receptor-linked activation or may reflect inadequacy of adrenergic blockade in standard clinical dosing.

Adrenergic beta-Antagonists↗
PubMed1997

Tedisamil increases coherence during ventricular fibrillation and decreases defibrillation energy requirements.

INTRODUCTION: Drugs which primarily prolong cardiac refractoriness decrease defibrillation voltage and energy requirements in animals and man. The effect of such drugs on ventricular fibrillation itself is not well understood. We hypothesized that tedisamil, an investigational antiarrhythmic drug which blocks Ito and IK repolarizing potassium channels, would increase organization of epicardial electrograms during ventricular fibrillation while it lowered defibrillation energy requirements. METHODS: We measured magnitude-squared coherence, a measure of spatial organization, and ventricular fibrillation (VF) cycle length, ventricular effective refractory period (VERP), and monophasic action potential duration (APD90) as well as defibrillation energy threshold (E50) at baseline and after 150 micrograms/kg of tedisamil (n = 13) or saline control (n = 6) in an open chest dog model. RESULTS: After tedisamil, mean magnitude-squared coherence increased by 132 +/- 133%, from 0.15 +/- 0.08 to 0.31 +/- 0.16 (P < 0.001); VF cycle length increased from 121 +/- 24 to 190 +/- 63 ms (P < 0.001) and became more regular, with the coefficient of variation between adjacent VF intervals decreasing from 14.1 +/- 6.9 to 3.9 +/- 2.2% (P < 0.001). Mean E50 decreased from 8.9 +/- 3.8 to 6.1 +/- 2.7 joules (P < 0.001); VERP increased from 158 +/- 30 to 201 +/- 31 ms (P < 0.001), and APD90 increased from 177 +/- 25 to 244 +/- 45 ms (P < 0.001) after tedisamil. No electrophysiologic parameter was changed after saline infusion. CONCLUSIONS: Tedisamil increases both spatial coherence and temporal regularity of ventricular fibrillation. These effects on 'order' during VF may be in part responsible for the observed reduction in defibrillation energy requirements.

Animals↗
PubMed1997

Electrophysiologic mechanisms of antiarrhythmic efficacy of a sotalol and class Ia drug combination: elimination of reverse use dependence.

OBJECTIVES: We sought to determine the electrophysiologic mechanisms explaining the efficacy of combination therapy with DL-sotalol and a type Ia drug in the treatment of ventricular tachycardia (VT). BACKGROUND: Combination antiarrhythmic drug therapy with low dose DL-sotalol plus a type Ia antiarrhythmic agent has been shown to prevent spontaneous and induced VT. The mechanisms underlying the efficacy of this drug combination have not been fully elucidated. METHODS: We studied 32 patients with spontaneous sustained VT by using programmed electrical stimulation in the drug-free condition and after treatment with DL-sotalol (average dose [mean +/- SE] 151 +/- 8 mg/day) and a class Ia agent (quinidine, 1,337 +/- 59 mg/day, or procainamide, 2,083 +/- 327 mg/day). Sustained VT was induced in all patients at baseline study, and induction was reattempted during drug therapy. Monophasic action potential duration at 90% repolarization (APD90) and ventricular effective refractory period (ERP) were recorded with use of a contact electrode. RESULTS: Ventricular ERP increased from 258 +/- 4 ms at baseline to 310 +/- 6 ms at a 600-ms drive cycle length (DCL600) with treatment (p < 0.001). APD90 increased from 288 +/- 6 ms by +10.1% at DCL600 and from 267 +/- 7 ms by +13.3% at a 400-ms drive cycle length (DCL400) (p < 0.001). Paced QRS duration increased from 141 +/- 3 to 158 +/- 6 ms at DCL400 (p < 0.05). At baseline, the shortest achieved coupling interval between successive propagated extrastimuli decreased progressively with respect to the first extrastimulus, following double and triple extrastimuli, at both DCL600 (-14.0% and -20.0%, respectively) and at DCL400 (-16.4% and -22.4%, respectively). This "peeling back" of refractoriness was attenuated on therapy with sotalol plus a class Ia antiarrhythmic agent to -6.7% and -10.5% (DCL600, p < 0.05), and -8.1%, -9.5% (DCL400, p < 0.05), for double and triple extrastimuli, respectively. The absolute prolongation of functional refractory periods by the drug combination increased with successive extrastimuli, from 55 +/- 6 ms for the V1V2 interval to 75 +/- 6 ms for V2V3 and 67 +/- 6 ms for V3V4 at DCL600, and from 51 +/- 5 ms for V1V2 to 69 +/- 6 ms for V2V3 and 74 +/- 7 ms for V3V4 at DCL400 (p < 0.001). CONCLUSIONS: The combination of low dose sotalol and a class Ia agent greatly prolongs refractoriness. The magnitude of the effect increases at shorter coupling intervals.

Action Potentials↗
PubMed1997

Electrocardiographic effects of fluoxetine and doxepin in patients with major depressive disorder.

Cardiovascular adverse effects are amongst the most serious observed with antidepressant drugs and are often due to effects on cardiac conduction and refractoriness. However, such electrophysiologic effects may not be evident when using conventional electrocardiographic measures. Forty patients with major depressive disorder (according to DSM-III-R criteria) were enrolled in a 6-week double-blind parallel group study of fluoxetine (N = 20) or doxepin (N = 20). Cardiac conduction (QRS duration) and repolarization (corrected QT interval, QTc), were measured using signal-averaged electrocardiograms and 12-lead electrocardiogram at baseline and after 2, 4, and 6 weeks of treatment. Patients taking doxepin (mean daily dosage at 6 weeks 169 +/- 42 mg) were similar to those taking fluoxetine (37 +/- 18 mg) for demographic variables and improvement in depression scores but volunteered more side effects (p = 0.011), especially dry mouth (p < 0.001) and dizziness/lightheadedness (p = 0.005). After 6 weeks, doxepin increased heart rate (69 +/- 12 to 81 +/- 13 beats per minute; p = 0.0003) and prolonged QTc (from 417 +/- 36 to 439 +/- 28 msec; p < 0.03); overall QRS duration was not prolonged but was correlated with serum doxepin concentrations (r = 0.78, p < 0.0001). Fluoxetine had no effect on QTc (428 +/- 24 msec at baseline vs. 430 +/- 24 msec at 6 weeks) or QRS duration (97 +/- 12 msec at baseline vs. 94 +/- 12 msec at 6 weeks). The standard 12-lead electrocardiogram showed no significant change in QRS or QTc for either drug. Using a sensitive measure of electrocardiographic effects, doxepin prolongs repolarization and may slow cardiac conduction. Fluoxetine has no measurable electrocardiographic effects, which suggests an increased safety margin for cardiac adverse effects. The ability of the signal-averaged electrocardiogram to resolve small changes in the electrocardiogram is useful in the assessment of drugs with subtle electrophysiologic effects.

Adult↗
PubMed1997

Dual device therapy in the setting of changing ICD technology: device-device interaction revisited.

This case report concerns an adverse device-device interaction between a replacement ICD and a dual chamber rate responsive pacemaker. It was observed that subtle changes in the design of sensing circuits between an older first-generation ICD and the newer third-generation ICD device led to unexpected and dramatic changes in the interactive behavior of a dual device system. The new ICD was connected to chronically implanted hardware. The sensing behavior of the newer ICD included a shorter time constant in the decay of the automatic gain control function, resulting in triple sensing of both the atrial and ventricular paced stimuli and the evoked QRS complex. Physicians should be aware of new design changes in the future so as to anticipate such interactions. In the setting of rapidly changing technology, extra caution must be exercised when choosing to implant two devices in the same patient.

Aged↗
PubMed1997

Serial measures of sinoatrial and atrioventricular nodal function in ambulatory patients.

We hypothesized that the outpatient assessment of SA and AV nodal (SAN, AVN) function could be a useful tool to determine the effectiveness of drugs and other treatments. We sought to examine the reproducibility, safety and ease of acquiring serial measurements of these parameters. Ten patients with permanent pacemakers underwent low current chest wall stimulation while their device was programmed to unipolar atrial triggered mode. Measurements at multiple conditioning drive train frequencies were obtained for: sinus nodal recovery time (SNRT); corrected sinus nodal recovery time (CSNRT); SA conduction time (SACT); AVN block cycle length (AVNBCL); and AVN effective refractory period (AVNERP). AVN function curves were also constructed. All studies were repeated after 2 weeks. Measures of sinus nodal and AVN function did not show significant differences between the two studies. The following co-efficients of correlation were obtained: SNRT800, r = 0.79; CSNRT800, r = 0.71; SNRT600, r = 0.71; CSNRT600, r = 0.44; SACT, r = 0.75; AVNBCL, r = 0.98; AVNERP800, r = 0.55; and AVNERP600, r = 0.99. AVN function curves did not significantly differ between week 1 versus week 2 at conditioning drive trains of either 800 ms or 600 ms. These data suggest that serial noninvasive electrophysiological measures of AVN and SAN function are reproducible over 2 weeks. Using data in this study, estimates of the sample size necessary for the evaluation of the effects of investigational drugs on the SAN and AVN in future studies are possible.

Arrhythmia, Sinus↗
PubMed1997

Transcutaneous T wave shock: a universal method for ventricular fibrillation induction.

Our objective was to develop a universal noninvasive method for VF induction. ICD implantation requires VF induction. Conventional rapid ventricular stimulation may fail to induce VF. Some ICDs can deliver low energy shocks on the T wave to induce VF. We hypothesized that an external dual chamber pacemaker and an external defibrillator could be configured to allow reliable VF induction with any ICD system. A surface ECG signal was delivered to the atrial channel of an external dual chamber DDD pacemaker. The 'AV' delay was adjusted so that the ventricular output of the pacemaker was delivered to an external defibrillator synchronized to deliver 5-50 J. Twenty-six patients at ICD implant or follow-up had VF induced in native rhythm (sinus rhythm or atrial fibrillation), or during a ventricular pacing train (3-8 beats at cycle length 500-880 ms). VF was successfully induced in 14 of 25 (56%) patients in native rhythm; and in 16 of 17 (94%) patients during pacing (P = 0.013). VF induction success rate was 36% in native rhythm (31/86 attempts) and 88% during pacing (69/78 attempts) (P < 0.001). The 'R' to shock interval was 269 +/- 31 ms in native rhythm and 257 +/- 48 ms during pacing. Energy delivered from the external defibrillator was 19 +/- 3 J in native rhythm and 21 +/- 6 J during pacing. We concluded that VF induction by synchronizing a small external shock to the T wave is a fast, effective way to reliably ensure arrhythmia induction with any ICD at implant or follow-up. This method is more successful during pacing than in sinus rhythm.

Defibrillators, Implantable↗
PubMed1997

Do permanent pacemakers need an insulative coating? Results of a prospective randomized double-blind study.

During conventional manufacturing of implanted pulse generators (IPGs), an insulative coating is often applied to prevent local muscle stimulation and myopotential sensing in unipolar pacing. This can limit the orientation of the IPG into its pocket, be a potential source of muscle stimulation via coating scratches, and result in an increase in IPG production costs. We hypothesized that advances in the design and construction of current IPGs and leads obviates the need for an insulative coating of the IPG. Using a double-blind prospective randomized design, 39 patients were implanted with either coated or uncoated otherwise identical IPGs (19 dual, 20 single chamber). All testing was done in unipolar and bipolar mode in both channels. A strength-duration curve for muscle stimulation was constructed for all patients with muscle stimulation. Myopotential sensing was established during isometric exercise. At 6-month follow-up when tested in unipolar mode, 3 of 15 (20%) patients with coated IPGs and 3 of 20 (15%) with uncoated IPGs had muscle stimulation at 5.0 V/1.5 ms or lower (P = NS). No patients in either population had muscle stimulation at their normally programmed output. Myopotential sensing occurred in all patients in unipolar mode at a mean of 2.29 +/- 1.3 mV and 2.73 +/- 1.14 mV for coated versus uncoated, respectively (P = NS). The statistical power of these negative observations was 80%. An insulative coating for pacemakers does not appear to alter sensing performance or cause a significant difference in the occurrence or characteristics of muscle stimulation.

Adult↗
PubMed1997

An overview of the management of electrical storm.

Electrical storm is defined as recurrent, hemodynamically destabilizing ventricular tachycardia or ventricular fibrillation occurring two or more times in a 24 h period, and usually requiring electrical cardioversion or defibrillation. Recent advances in the understanding of the pathogenesis of this serious arrhythmia and in its pharmacological management have improved the prognosis for patients experiencing electrical storm. In this article, several different clinical syndromes of electrical storm and the management of each are examined.

Anti-Arrhythmia Agents↗
PubMed1997

Management of supraventricular tachycardia in the emergency department.

While supraventricular tachycardia is a common condition and seldom leads to serious consequences, it can be challenging to treat. Optimal management requires an accurate diagnosis, especially in the distinction between regular and irregular tachycardias; as well as an understanding of the mechanism responsible for the arrhythmia. In this article, the acute management of supraventricular tachycardias as they present in the emergency department is discussed, based on the underlying electrophysiological principles of arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1997

Emergency arrhythmia management: an assessment of learning needs.

For physicians working in emergency departments, optimum management of patients with arrhythmias is an important skill. To assess the learning needs of Canadian emergency physicians with respect to arrhythmias, the members of the Canadian Association of Emergency Physicians (CAEP) were surveyed. The survey assessed perceived learning needs and included 11 scenarios assessing physician knowledge. Of 883 surveys distributed, 278 were returned, a response rate of 31.5%. The topic areas ranked most highly by respondents in terms of perceived learning needs were management of ventricular arrhythmias (especially electrical strom), and clinical use of oral and intravenous antiarrhythmic drugs, particularly the clinical use of intravenous amiodarone. The assessment of knowledge showed that the respondents managed most arrhythmias in accordance with published guidelines, although the management of some wide complex tachyarrhythmias was not optimal. These results will be used to guide an ongoing program of continuing medical education.

Anti-Arrhythmia Agents↗
PubMed1997

[Etiologies of electric storm].

The electrical storm is defined as recurrent ventricular tachycardia or fibrillation leading to cardiac shock occurring two or more times within 24 hours and usually requiring cardioversion or defibrillation. Recent advances in our understanding of this severe arrhythmia and its pharmacological treatment have improved the prognosis of these patients. The authors review several clinical syndromes of the electrical storm and the treatment of each.

Aged↗
PubMed1996

Hyperaldosteronism and sudden cardiac death.

From a database of 130 implantable cardiac defibrillator recipients, 2 patients (1.5%) with sudden cardiac death as a presenting symptom, leading to diagnosis of primary hyperaldosteronism, are described. This is a newly described cause of sudden cardiac death, possibly more frequent than suspected, which should be considered in patients with malignant arrhythmias and hypokalemia.

Adult↗