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Biomedical subjects

E L Pritchett

Publications and source records attributed to E L Pritchett.

At least 55 records · Page 3Linked to original sources
PubMed1989

Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy. A multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Flecainide Supraventricular Tachycardia Study Group.

Paroxysmal atrial fibrillation (PAF) is a problematic clinical arrhythmia that is usually symptomatic. Unfortunately, few adequate trials and trial methods are available for assessment of the value of therapy, and traditional treatment has often been ineffective or associated with unacceptable side effects. Transtelephonic monitoring is a new method that allows evaluation of paroxysmal arrhythmias and arrhythmia-related symptoms in outpatients. We used a patient-initiated transtelephonic monitor system to evaluate the potential of flecainide, a class 1C antiarrhythmic, in prevention of symptomatic recurrences of PAF. Sixty-four patients qualified for the study (two or more PAF attacks documented within a 4-week baseline period) and entered a dose-finding phase to determine drug tolerance. Dose was incremented at weekly intervals from 200-300 and finally to 400 mg/day. The largest dose that was well tolerated was selected for the 4-month, double-blind, randomized, crossover comparison with placebo. Fifty-five patients entered and 53 received both treatments in the double-blind phase; 48 of these patients without protocol violations were evaluable for efficacy comparisons. Evaluable patients had undergone an average of 3.8 previous drug trials (range, 1-8); 30 were men, 18 had hypertension, and 14 had ischemic heart disease. The study demonstrated a highly significant correlation (p less than 0.0001) between perceived symptoms and documented PAF by transtelephonic monitoring. The rate of symptoms and PAF attacks was also significantly reduced by therapy (median dose, 300 mg/day). The first PAF attack occurred after a median of 3 days on placebo versus 14.5 days on flecainide (p less than 0.001) therapy. Similarly, the time interval between attacks was lengthened, from a median of 6.2 days on placebo to 27.0 days on flecainide (p less than 0.001) therapy. PAF was prevented in 15 patients (31%) during flecainide and four (9%) during placebo therapy (p = 0.013). However, during the study, 13 patients dropped out, seven because of adverse effects (five cardiac), five for other reasons, and one because of cardiac arrest/death. Adverse cardiac events occurred in a total of seven patients (11%) during flecainide therapy. Thus, transtelephonic monitoring is a useful method for documentation of the occurrence of paroxysmal arrhythmias such as PAF and its related symptoms during daily living and for assessment of new therapies in an outpatient setting.

Atrial Fibrillation↗
PubMed1988

Clinical behavior of paroxysmal atrial tachycardia.

Paroxysmal atrial tachycardia is a familiar arrhythmia that has been studied extensively for the past decade using intracardiac recording and programmed electrical stimulation. These studies have thoroughly documented the mechanisms of this arrhythmia and its associated atrioventricular conduction abnormalities, but little is known about the spontaneous clinical behavior of this arrhythmia. A group of 34 patients with paroxysmal atrial tachycardia were studied using telephone transmission of the electrocardiogram to document recurrent tachycardia. When antiarrhythmic therapy was withdrawn, median time to the first recurrence of tachycardia was 19 days, mean heart rate during spontaneous tachycardia was 203.5 +/- 34.9 beats/min, and the median duration of an attack was 20 minutes. In a group of patients who were followed while many consecutive attacks were documented, the time intervals between attacks were found to be uncorrelated and to fit an exponential probability distribution (i.e., the occurrence of paroxysmal atrial tachycardia behaved like a Poisson process). Paroxysmal atrial tachycardia does not occur in a chaotic and unpredictable fashion; it is an event that occurs according to common probability models.

Electrocardiography↗
PubMed1988

Pharmacokinetic and pharmacodynamic interactions of propafenone and cimetidine.

The pharmacokinetics and pharmacodynamics of the extensively metabolized antiarrhythmic agent propafenone were assessed alone and during concomitant administration of cimetidine. Twelve healthy subjects were given successively the following treatments: propafenone 225 mg q8h plus cimetidine placebo; cimetidine 400 mg q8h plus propafenone placebo; and propafenone 225 mg plus cimetidine 400 mg q8h. After a minimum of 5 days on each regimen, plasma drug concentrations and electrocardiogram conduction intervals were measured during a drug washout period. The maximum concentration of propafenone in plasma was 993 +/- 532 ng/mL when propafenone was given alone compared with 1230 +/- 591 ng/mL when propafenone was given with cimetidine (P = .0622). Differences in tmax, t1/2, and Cp ss did not approach statistical significance when propafenone alone was compared with propafenone plus cimetidine. When compared with cimetidine, propafenone significantly increased the PR interval from 161 +/- 5 msec to 192 +/- 6 msec (P less than .01) and the QRS duration from 89 +/- 3 msec to 98 +/- 4 msec (P less than .01). Combination therapy caused a modest additional increase in QRS duration to 103 +/- 3 msec (P less than .01). In conclusion, cimetidine caused small changes in propafenone pharmacokinetics and pharmacodynamics; but these changes are unlikely to be clinically important.

Adult↗
PubMed1988

Detection of corticosteroid type I binding sites in heart.

Both high affinity (type I) and low affinity (type II) corticosteroid binding sites are detected in cytosolic extracts of atrial and ventricular tissue when [3H]aldosterone is used as the ligand. In the presence of RU-28362, which blocks binding of [3H]hormone to the low affinity type II sites, [3H]aldosterone binds to a single class of high affinity sites. The apparent Kd for binding of the hormone to the type I sites was 1.0 nM in atrial cytosol and 0.75 nM in ventricular cytosol. The concentration of type I sites in atrial (12 fmol/mg protein) and ventricular cytosols (11 fmol/mg protein) is comparable to reported values in renal (17-31 fmol/mg protein) cytosol. Activation of the type I hormone-receptor complexes to the DNA-binding form was examined using chromatography on DEAE-Sephadex anion-exchange resin. The unactivated hormone-receptor complex elutes at a concentration of 400 mM KCl. Following heat treatment (25 degrees C, 30 min) the [3H]aldosterone-receptor complex is transformed to a low salt eluting (200 mM KCl), DNA-binding form. Activation is blocked by inclusion of 10 mM sodium molybdate during heat treatment.

Adrenal Cortex Hormones↗
PubMed1988

Designing clinical trials for paroxysmal atrial tachycardia and other paroxysmal arrhythmias.

Paroxysmal atrial tachycardia may be useful as a model for designing clinical trials of paroxysmal tachycardia. Individual occurrences of paroxysmal atrial tachycardia are clinically independent events, and the time periods between events follow an exponential probability distribution; i.e. paroxysmal atrial tachycardia behaves like a Poisson process. We propose that treatment of paroxysmal atrial tachycardia can be studied efficiently using a clinical trial with a two period cross-over design in which placebo and investigational therapy are delivered in random order. A screening phase, dose ranging phase, and both limbs of a cross-over plane can be completed in 180 days or less in each patient.

Anti-Arrhythmia Agents↗
PubMed1988

Circadian occurrence of symptomatic paroxysmal supraventricular tachycardia in untreated patients.

Fifty-two patients with paroxysmal supraventricular tachycardia were studied to determine whether there was a circadian pattern to the occurrence of this arrhythmia. Antiarrhythmic therapy was discontinued, and patients were followed until they had one recurrence of tachycardia documented by telephone transmission of the electrocardiogram. By least-squares analysis, the times of day that the 52 attacks (one from each patient) occurred were fit to a sinusoidal density function with a period of 24 hr. The highest relative incidence of tachycardia was at 4 P.M.; tachycardia was five times more likely to occur at 4 P.M. than at 4 A.M., the time of the lowest relative incidence. A second attack of tachycardia was recorded from 35 of the 52 patients. The times of the two attacks in individual patients were found to be independent; thus the times of day at which the second attacks occurred were used as a test set for the distribution estimated from the first. The empirical distribution for the times from the 35 second attacks was compared with the distribution function estimated from the 52 first attacks, and there was no significant departure; this finding confirmed the circadian pattern. Since the relative incidence of attacks of paroxysmal supraventricular tachycardia is higher in the afternoon, it may be helpful to target antiarrhythmic therapy to that time of day.

Adult↗
PubMed1987

Value of the 12-lead electrocardiogram in discriminating atrioventricular nodal reciprocating tachycardia from circus movement atrioventricular tachycardia utilizing a retrograde accessory pathway.

The value of the 12-lead electrocardiogram for distinguishing atrioventricular (AV) nodal reciprocating tachycardia from circus movement AV tachycardia utilizing a retrograde accessory pathway was studied in 100 patients with narrow QRS complex tachycardia. Intracardiac electrograms showed AV nodal reciprocating tachycardia in 40 patients and circus movement AV tachycardia in 60. The 12-lead electrocardiograms recorded during tachycardia were randomly sorted and reviewed by 4 experienced cardiac electrophysiologists who were blinded to the diagnosis associated with each tracing, the relative proportion of each arrhythmia and the hypotheses to be tested. Each reviewer was asked to indicate the location of the P wave relative to the QRS complex, electrical axis of the P wave in the frontal and horizontal planes and presence or absence of QRS alternation, and to interpret the most likely mechanism. The performance of published electrocardiographic criteria to differentiate AV nodal reciprocating tachycardia from circus movement AV tachycardia was evaluated. The overall accuracy of the reviewers' interpretations was 75%, similar to the accuracy of the predefined criteria when applied by these observers (71% correct, difference not significant). Interobserver agreement of reviewer interpretations was 76% and the intraobserver agreement was 78%. Features associated with circus movement AV tachycardia by univariable analysis were P waves after the QRS complex, faster tachycardia rates and QRS alternation. Multivariable analysis showed that only the location of the P wave relative to the QRS complex was independently associated with the mechanism of tachycardia (p = 0.002). QRS alternation was found by multivariate analysis to be associated with the rate but not the mechanism of the tachycardia.

Diagnosis, Differential↗
PubMed1987

Pharmacodynamics and pharmacokinetics of oral pirmenol.

The efficacy, pharmacokinetics, and pharmacodynamics of pirmenol, a class Ia antiarrhythmic agent, were studied in patients with frequent symptomatic premature ventricular complexes (PVCs). Pirmenol was given every 12 hours to eight patients in a dose-ranging protocol, and median PVC suppression of 94% (range 72% to 100%) was achieved. The median effective pirmenol dose was 300 mg/day (range 200 to 500 mg/day), and mean (+/- SD) trough plasma pirmenol concentration at the effective dose was 0.98 +/- 0.29 micrograms/ml. The mean half-life of elimination was 10.5 +/- 2 hours. There was considerable overlap among patients with respect to plasma pirmenol concentration and times at which PVC frequency returned to 25%, 50%, and 75% of baseline during drug washout trials. Altering pirmenol's dose interval (while maintaining a constant daily dose) from 12 to 6 hours did not improve drug efficacy. Pirmenol was given to seven patients for long-term therapy (24 to 44 months). Median PVC suppression at 24 months was 70%. Pirmenol is safe and well tolerated, and it can be administered twice daily for PVC suppression.

Administration, Oral↗
PubMed1987

Pharmacokinetics and pharmacodynamics of esmolol administered as an intravenous bolus.

Esmolol is a new ultra-short-acting beta-adrenergic receptor blocking agent that may be useful in the treatment of patients with heart disease. We gave esmolol as an intravenous bolus injection (over 30 seconds) to 12 healthy men in a dose-ranging study; each subject received two doses. Our dosing schedule began with 30 mg in the first subject and ended with 100 mg and 150 mg in the final four subjects. We measured blood esmolol concentration, PR interval, QRS duration, QTc interval, cardiac cycle, systolic blood pressure, and diastolic blood pressure. Esmolol doses of 150 mg produced blood esmolol concentrations of 0.868 to 1.47 micrograms/ml. The peak PR interval recorded after esmolol was significantly longer than the control PR interval in four subjects who received 100 and 150 mg doses (192 +/- 7.9 msec vs. 177 +/- 10.6 msec; P = 0.00002). Peak prolongation of the PR interval was recorded 6 to 10 minutes after the bolus, at which time blood esmolol concentrations were negligible. Esmolol did not consistently affect any other pharmacodynamic variable. Giving esmolol as an intravenous bolus injection may be a simple alternative to loading and maintenance infusion in some clinical settings.

Adrenergic beta-Antagonists↗
PubMed1987

Effects of bolus injection of esmolol in healthy, exercising subjects.

Esmolol is an investigational ultra-short-acting beta-adrenergic blocker that has potential application in many clinical cardiology settings. The purpose of this study was to investigate the effect of a bolus dose of esmolol on heart rate, blood pressure, and PR interval in healthy, exercising male subjects. We gave a single esmolol bolus over 30 seconds to 13 men who exercised to a predetermined target heart rate. Each subject performed the exercise protocol twice, receiving a different dose between 10 and 300 mg each time. An additional eight subjects received two esmolol boluses 5 minutes apart while performing the same exercise protocol. Esmolol doses of 180 mg or greater caused a 13% to 18% decrease in heart rate, an 11% to 18% decrease in blood pressure, and a 13% to 22% prolongation of the PR interval. The median time to peak esmolol effect was 1 minute for heart rate, 2 minutes for blood pressure, and 4 minutes for PR interval. The median time required to recover 50%, 75%, and 90% of the decrement in heart rate was 8, 10, and 13 minutes, respectively. The rapid onset and disappearance of esmolol effects may make it an appealing drug in acute care settings.

Adult↗
PubMed1986

Effects of sustained intravenous diltiazem infusion in healthy persons.

A 3-stage infusion of diltiazem was tested in 8 subjects for up to 48 hours: a bolus injection (10 mg over 3 minutes), a rapid loading infusion (20 mg over 30 minutes) and a maintenance infusion (10 mg/hour to the end of the study). This regimen produced stable median plasma diltiazem concentrations of approximately 150 ng/ml. The median half-life of elimination for diltiazem was 206 minutes (range 144 to 452) and median total clearance was 980 ml/min (range 665 to 1,907). The PR interval lengthened 10 to 18% during the maintenance infusion in 7 subjects; in 1 subject atrioventricular nodal Wenckebach conduction was recorded during the rapid loading infusion. Systolic blood pressure decreased from 124 +/- 7 mm Hg (mean +/- standard deviation) during the control period to 121 +/- 8 mm Hg during the rapid loading infusion (p = 0.03 compared with control) and to 117 +/- 7 mm Hg (p = 0.04 compared with control) during the maintenance infusion. Heart rate did not change. PR interval and blood pressure returned to control levels within 4 hours after the infusion was stopped. Loading and maintenance infusion may be an attractive method of administering diltiazem when stable drug concentrations are required for prolonged periods.

Adult↗
PubMed1986

Observations on the occurrence of atrial fibrillation in paroxysmal supraventricular tachycardia.

Paroxysmal supraventricular tachycardia (PSVT) and atrial fibrillation (AF) are both supraventricular arrhythmias, but their mechanisms are completely different. This study determines the incidence of symptomatic AF in a group of patients followed closely during routine outpatient care for PSVT. Thirty-nine patients with PSVT were followed for up to 4 years using telephone transmission of the electrocardiogram to document symptomatic arrhythmias. The cumulative proportion of patients who had AF was calculated using the Kaplan-Meier life-table method. In addition, we examined the importance of clinical variables traditionally believed to influence the occurrence of AF. The cumulative proportion of patients who had AF during follow-up was 13% at 3 months, 16% at 6 months, 22% at 1 year and 29% at 2 years. In most patients the start of AF was documented during an attack of PSVT rather than de novo as another primary arrhythmia. PSVT occurred significantly earlier during an observation period without treatment in patients in whom AF developed (p = 0.03). The occurrence of AF was not related to age, number of years of PSVT, heart rate during tachycardia or coexistent heart disease.

Adult↗
PubMed1986

Career choices of 135 cardiology trainees at Duke University Medical Center from 1970 to 1984.

Alarm has been expressed at recently presented evidence showing that diminishing numbers of physicians are entering academic careers. The experience of the cardiology training program at a university medical center between 1970 and 1984 was reviewed to determine the career paths chosen by its trainees. During the study period, 135 physicians received training. Between 1970 and 1978 the percentage of trainees making academic medicine their initial career choice fluctuated considerably. Beginning in 1978, the percentage entering academic medicine steadily increased; in the most recent class, 8 of 9 trainees accepted academic faculty positions. Among 72 former trainees who joined an academic faculty after finishing training, approximately 7% per year left academic medicine for clinical practice. The median length of an academic career was 10 years. Individual institutions may be able to reverse the national trend of trainees making clinical practice their initial career choice. However, physicians who leave academic medicine for clinical practice may continue to deplete faculty ranks.

Academic Medical Centers↗
PubMed1986

Incidence of symptomatic tachycardia in untreated patients with paroxysmal supraventricular tachycardia.

The purpose of this article is to investigate the occurrence of symptomatic paroxysmal supraventricular tachycardia (PSVT) in untreated patients and to assess factors that influenced its occurrence. We studied 34 patients with this arrhythmia during an observation period in which they received no antiarrhythmic drug therapy for up to 90 days. Recurrence of PSVT was documented by telephone transmission of the electrocardiogram. Each patient was allowed to have exactly one episode of tachycardia before being removed from the study. We measured how long patients remained free of their tachycardia (the tachycardia-free period) and heart rate during tachycardia. Twenty-nine of the 34 patients had an attack of symptomatic tachycardia within the 90-day observation period. The proportion of patients who had not had any symptomatic PSVT by each day of follow-up was calculated using the Kaplan-Meier method as follows: 75% by day 3, 50% by day 19, 25% by day 36, and 17% by day 90. Patients with any other heart or lung disease had significantly shorter tachycardia-free periods. The mean heart rate during spontaneous tachycardia was 203.5 +/- 34.9 beats per minute (range, 142 to 288 beats per minute). Patients with longer tachycardia-free periods had significantly faster heart rates during tachycardia.

Adult↗