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Biomedical subjects

L N Horowitz

Publications and source records attributed to L N Horowitz.

At least 55 records · Page 3Linked to original sources
PubMed1987

Autonomic modulation of aminophylline influence on the electrophysiological effects of adenosine and adenosine triphosphate in the canine heart.

The influence of aminophylline, a competitive antagonist of adenosine, on the chronotropic and dromotropic effects of adenosine and adenosine triphosphate was studied in pentobarbital anaesthetised dogs under various modifications of the autonomic nervous tone. Adenosine and adenosine triphosphate (3 mumol.kg-1 each) were rapidly (greater than or equal to 1 s) injected into the right atrium during both sinus rhythm and right atrial pacing (cycle length 300 ms) before and after infusion of aminophylline (5 mg.kg-1) (n = 21) as well as after increasing doses of aminophylline (n = 10). Some dogs underwent either muscarinic blockade with atropine (0.2 mg.kg-1) (n = 10), or beta adrenergic blockade with propranolol (1 mg.kg-1) (n = 10), or complete autonomic blockade with atropine and propranolol (n = 10). Aminophylline (5 mg.kg-1) antagonised the negative chronotropic and dromotropic effects of adenosine triphosphate and adenosine in dogs pretreated with atropine or atropine plus propranolol but did not affect them in autonomically intact dogs. In addition, the electrophysiological effects of adenosine were antagonised by only the highest doses of aminophylline in autonomically intact dogs and by aminophylline (5 mg X kg-1) in dogs pretreated with propranolol. It was concluded that (a) alteration of the electrophysiological effects of adenosine triphosphate and adenosine by aminophylline is appreciably influenced by the autonomic nervous tone and (b) autonomic blockade is required for the manifestation of the antagonism by aminophylline of the electrophysiological action of adenosine and adenosine triphosphate.

Adenosine↗
PubMed1986

Bepridil hydrochloride for treatment of benign or potentially lethal ventricular arrhythmias.

To define the efficacy and safety of a new once-a-day calcium antagonist, bepridil, 21 patients with frequent ventricular premature complexes (VPCs) underwent a 14-day inpatient monitored trial. After Holter monitoring during placebo administration, patients underwent 2 days of a loading dose of bepridil followed by 12 days of bepridil, 400 mg/day. Holter monitoring during therapy showed that 10 patients (48%) had more than a 70% reduction in VPC frequency and 8 of 16 patients (50%) at least a 95% reduction in frequency of nonsustained ventricular tachycardia. Gastrointestinal and central nervous system side effects considered to be mild occurred in 13 patients (62%). One patient had an asymptomatic increase in VPC frequency and another had sustained ventricular tachycardia associated with a loading dose of 900 mg of bepridil. Thus, bepridil has moderate antiarrhythmic efficacy in patients with ventricular arrhythmias, but further definition of its potential for causing proarrhythmia must be determined.

Bepridil↗
PubMed1986

Encainide in lethal ventricular arrhythmias evaluated by electrophysiologic testing and decrease in symptoms.

Encainide hydrochloride has distinct electrophysiologic properties that suggest active antiarrhythmic properties. Encainide has been administered both intravenously (0.5 to 1.7 mg/kg) and orally (100 to 300 mg/day) to patients with lethal ventricular arrhythmias--ventricular tachycardia (VT) and ventricular fibrillation--and evaluated by electrophysiologic testing. In 62 patients with inducible sustained VT, intravenous encainide prevented initiation in 13 (21%). In 57 patients with refractory sustained VT, oral encainide prevented initiation of VT by programmed stimulation in 17 (30%). The results obtained with intravenous and oral encainide in the same patient were usually concordant (93%). Encainide may worsen ventricular arrhythmia, most typically by converting nonsustained VT into sustained VT during electrophysiologic testing. In patients with lethal ventricular arrhythmia, analysis of symptoms before and during chronic encainide therapy showed that the number and severity of arrhythmia-related symptoms were reduced. Encainide appears to be a useful antiarrhythmic agent.

Administration, Oral↗
PubMed1986

Plasma norepinephrine in exercise-induced ventricular tachycardia.

The relation between plasma norepinephrine levels and the occurrence of ventricular tachycardia during exercise testing was prospectively evaluated in 17 patients. Ten patients had reproducible ventricular tachycardia exclusively during exercise or recovery, or both; 7 patients had ventricular tachycardia only during ambulatory electrocardiographic monitoring. The two groups did not differ in age, exercise duration, left ventricular ejection fraction at rest, heart rate throughout the exercise protocol, rest QTc interval, change in QTc interval during exercise, the presence of coronary artery disease or exercise-related myocardial ischemia. Furthermore, there was no difference between groups in plasma norepinephrine levels at rest, peak exercise or in the recovery period. Myocardial ischemia was detectable by thallium perfusion scan in only 2 of the 10 patients with exercise-induced ventricular tachycardia. The 10 patients with exercise-induced ventricular tachycardia underwent repeat exercise testing immediately after maximal intravenous beta-adrenergic blockade with propranolol. Although they had no change in exercise duration, ventricular tachycardia did not occur in 9 of these 10 patients. Plasma norepinephrine levels were significantly decreased compared with levels before beta-adrenergic blockade (p less than 0.0002). Thus, plasma norepinephrine levels do not distinguish patients with reproducible exercise-induced ventricular tachycardia from otherwise comparable patients. Propranolol is highly effective in abolishing this arrhythmia and this effect is associated with decreased norepinephrine levels.

Adult↗
PubMed1986

Flecainide: steady state electrophysiologic effects in patients with remote myocardial infarction and inducible sustained ventricular arrhythmia.

The effect of flecainide in 24 patients with inducible sustained ventricular arrhythmia and a history of remote myocardial infarction was determined. Flecainide was administered in oral doses individually adjusted to suppress all spontaneous ventricular tachycardia and 80% of ventricular premature complexes on 24 hour ambulatory (Holter) electrocardiography. Antiarrhythmic therapy, as assessed by Holter monitoring, was adequate in 20 (83%) of the study patients at a mean dose of 144 +/- 28 mg every 12 hours; the mean plasma flecainide level was 583 +/- 329 ng/ml. In 18 patients, the mean sinus cycle length, sinus node recovery time and atrial, atrioventricular nodal and ventricular refractory periods were unchanged. The AH interval increased by 15 +/- 15%, the HV interval by 35 +/- 32% and the QRS duration by 24 +/- 21%. Toxicity or failure to suppress ventricular premature complexes and ventricular tachycardia by Holter monitoring precluded electrophysiologic study with flecainide in four patients; two patients refused electrophysiologic study with flecainide for nonmedical reasons. Ventricular tachycardia was not inducible in 4 (22%) of 18 patients receiving flecainide. Sustained arrhythmia remained inducible in 14 patients (78%) despite evidence of antiarrhythmic efficacy on Holter monitoring, but the rate of the induced ventricular tachycardia was slower and symptoms were alleviated during ventricular tachycardia in 10 (56%) of 18 patients. The 4 patients who had no inducible ventricular tachycardia with flecainide, and the 10 patients who had inducible ventricular tachycardia with a longer cycle length and alleviation of their symptoms, have been followed up as outpatients for 16 +/- 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Utility of ambulatory electrocardiographic monitoring for predicting recurrence of sustained ventricular tachyarrhythmias in patients receiving amiodarone.

The prognostic implications of changes in ventricular ectopic activity on serial 24 hour ambulatory electrocardiographic (Holter) recordings were prospectively evaluated in 107 patients with a history of sustained ventricular tachyarrhythmias treated with amiodarone for at least 30 days. Twenty-seven patients (25%) had insufficient ventricular ectopic activity (less than 10 ventricular premature complexes/h and no repetitive forms) on baseline Holter recordings for serial statistical analysis. In 53 (66%) of the remaining 80 patients, serial 24 hour Holter monitor recordings showed efficacy of treatment, defined as a 75% decrease in ventricular premature complexes, a 95% decrease in ventricular couplets and absence of ventricular tachycardia. During a mean follow-up period of 14.2 +/- 9.9 months, 34 (32%) of the 107 patients had recurrence of a sustained ventricular tachyarrhythmia. Holter recording correctly predicted nine recurrences and correctly identified 37 patients who did not experience a recurrence. Holter efficacy failed to predict recurrence of a sustained ventricular tachyarrhythmia in 16 patients, and 18 patients remained free of recurrence despite failure to achieve Holter efficacy. The positive predictive value of Holter monitoring efficacy was 33% and the negative predictive value was 70%; however, these differences were not statistically significant by chi-square analysis. Similar results were obtained using Holter recordings performed relatively early in therapy (6 weeks and 4 months). Of the 27 patients without significant ventricular ectopic activity on the baseline Holter recording, 9 had an arrhythmia recurrence despite continued infrequent ventricular premature complexes and no repetitive forms on subsequent recordings. The recurrence rate in this group (33%) was similar to the overall recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Combination antiarrhythmic drug therapy for ventricular tachyarrhythmias.

New antiarrhythmic drug regimens are constantly being sought because of the relatively low efficacy rates of standard antiarrhythmic agents in preventing induction of ventricular tachyarrhythmias; the application of these agents is also limited due to serious or debilitating side-effects. The combination of two antiarrhythmic agents with complimentary electrophysiologic activities and differing toxicities might offer significant advantages in overcoming the drawbacks of standard antiarrhythmic drug therapy. A knowledge of the pharmacodynamics of the major classes of antiarrhythmic agents will allow informed choices of drugs for use in combination therapy. Judging antiarrhythmic drug efficacy is a complex problem, requiring an understanding of the influence of the arrhythmia monitoring technique, arrhythmia morphology and the response to previous drugs on drug efficacy rates, so that accurate comparisons of drug effectiveness can be made among different agents or combinations. A number of combination therapies have been tested for suppression of complex ventricular ectopy, nonsustained ventricular tachycardia and sustained ventricular tachycardia and ventricular fibrillation. The most successful combinations have been those using class IA and IB agents and class IA and II agents. In general, these combinations tend to show higher efficacy rates in suppressing all forms of ventricular ectopy and ventricular tachyarrhythmias, and usually have a lower incidence of toxic side-effects compared with individual agents alone. On the basis of these initial results, it seems warranted to perform further studies to explore these combinations in larger populations and to test new combinations developed on the basis of pharmacodynamic principles.

Adrenergic beta-Antagonists↗
PubMed1986

Clinical cardiac electrophysiology: history, rationale, and future.

The discipline of clinical cardiac electrophysiology has evolved over the past 40 years. Intense interest has resulted in the clinical application of intracardiac electrophysiologic techniques over the past 20 years. Clinical cardiac electrophysiologic studies have developed since the demonstration that programmed electrical stimulation could be performed in the human heart to evaluate tachyarrhythmias and that cardiac electrical activity that could not be detected on the body surface could be measured with intracardiac electrodes. Clinical electrophysiologic techniques have evolved for the assessment of sinus nodal, AV nodal, and His-Purkinje system function. The evaluation of tachyarrhythmias has progressed rapidly, and pharmacologic, device, and surgical therapy can now be guided by electrophysiologic studies. Invasive electrophysiologic studies have confirmed the utility of noninvasive electrocardiographic analysis and in several circumstances have proved that invasive studies are not necessary. Alternatives to invasive electrophysiologic evaluation continue to be debated. It is clear that when performed by well-trained individuals in appropriately equipped laboratories, electrophysiologic studies are safe and can be shown to be beneficial. Clinical cardiac electrophysiology continues to evolve, and problems of uniformity of methods, definitions of terms, and protocols remain to be resolved. The future of clinical cardiac electrophysiology appears to be one of continued evolution of techniques, refinement of indications, and continued clinical applications.

Arrhythmias, Cardiac↗
PubMed1986

Electrophysiologic evaluation of patients with preexcitation syndromes.

The evaluation of patients with preexcitation syndromes includes the electrophysiologic documentation of preexcitation and an evaluation of the functional status of the accessory pathway. Electrophysiologic techniques allow identification of the site of the accessory pathway and its participation in arrhythmias. Electrophysiologic testing can also be used to evaluate pharmacologic, device, and surgical therapy.

Electrodiagnosis↗
PubMed1985

Electrophysiology of esmolol.

The electrophysiologic characteristics of esmolol were studied in 14 patients. Ten men and 4 women, mean age 57 years, were electrophysiologically evaluated at baseline, and also at 4 to 8 minutes after the administration of a maintenance infusion of esmolol. Plasma samples for esmolol blood levels were drawn at 10 minutes of the maintenance infusion, at the end of the maintenance infusion and 30 minutes after the maintenance infusion was discontinued. Results of this study showed that esmolol has typical beta-blocker electrophysiologic effects. Its major action was on sinus node function; it prolonged this basic sinus cycle length but had no significant effect on intrinsic automaticity as reflected by the corrected sinus node recovery time and sinoatrial conduction. Direct effects on atrioventricular (AV) nodal function were reflected by effects on AV nodal conduction and refractoriness. There was no direct effect on atrial function and, as expected, no effect on His-Purkinje or ventricular function. The intensity of esmolol's electrophysiologic effects on sinus node function, AV nodal conduction and AH interval is comparable to those of other beta blockers.

Adrenergic beta-Antagonists↗
PubMed1985

Comparative efficacy and tolerance of esmolol to propranolol for control of supraventricular tachyarrhythmia.

This multicenter, double-blind, randomized, parallel study compared the effectiveness and tolerance of intravenous esmolol with intravenous propranolol in patients with supraventricular tachyarrhythmia (heart rate [HR] greater than 120 beats/min). Efficacy was evaluated in 53 patients receiving esmolol and in 57 patients receiving propranolol. Patients randomized to esmolol received infusions of various doses of esmolol ranging from 50 to 300 micrograms/kg/min (each dose infused for 5 minutes) over a 30-minute titration period with intermittent placebo boluses of propranolol. Those randomized for propranolol received 1 mg/min for the first 3 minutes, and then another 3 mg from minutes 5 to 8 with continuous placebo esmolol infusion during the 30-minute titration period. A therapeutic response, defined by 20% or greater reduction in HR, HR less than 100 beats/min or conversion to normal sinus rhythm, was achieved in 72% of patients on esmolol compared with 69% of patients on propranolol (difference not significant). The therapeutic response was maintained in 67% of patients on esmolol and 58% of patients on propranolol (difference not significant) during a 4-hour maintenance period. Conversion to normal sinus rhythm occurred in 14% of esmolol patients and 16% of propranolol patients during titration and 10% of esmolol and 8% of propranolol patients during maintenance. After discontinuation of study drugs, a more rapid reversal of the reduction in HR was observed in esmolol patients compared with those patients receiving propranolol. Adverse reactions were seen in 29 (45%) patients on esmolol and 11 (18%) patients on propranolol. The principle adverse reaction was hypotension, which was predominantly asymptomatic and found in 23 patients receiving esmolol and 4 receiving propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1985

Incidence of proarrhythmic effects from quinidine in the outpatient treatment of benign or potentially lethal ventricular arrhythmias.

To determine the prevalence and importance of proarrhythmic events secondary to the initiation of quinidine therapy in outpatients with benign or potentially lethal ventricular arrhythmias, the data from 360 patients treated with quinidine as part of 3 outpatient drug trials were retrospectively reviewed. These patients had at least 30 ventricular premature complexes per hour during placebo treatment and had no evidence of unstable clinical states, hypokalemia, digitalis toxicity, atrial fibrillation or a prolonged QT interval (longer than 0.50 second). The quinidine dose varied from 200 to 400 mg 4 times a day for 2 to 4 weeks. Proarrhythmic effect was defined on Holter monitoring as a 400% increase in frequency of ventricular premature complexes, the presence of new ventricular tachycardia not previously identified or a 10-fold increase in the number of beats of ventricular tachycardia. There was no difference in the demography, response to quinidine therapy or side effects on quinidine among the 3 trials. Six of 360 patients (2%) had a proarrhythmic response and none of these patients had hemodynamic symptoms, required hospitalization or died from the proarrhythmic event. Thus, quinidine can be safely initiated to outpatients who meet the inclusion criteria cited herein.

Ambulatory Care↗
PubMed1985

Efficacy of combination therapy with mexiletine and a type IA agent for inducible ventricular tachyarrhythmias secondary to coronary artery disease.

The efficacy of combination therapy using a type IA agent (quinidine or procainamide) and a type IB agent (mexiletine) in suppressing inducible sustained ventricular tachyarrhythmias was studied in 23 patients undergoing serial drug testing with programmed stimulation. All patients had coronary artery disease (CAD) with previous myocardial infarction and abnormal left ventricular function (mean ejection fraction 35%). Fifty-five percent of the patients presented with syncope or cardiac arrest. In 19 patients therapy had failed during empiric trials of 1 to 3 antiarrhythmic agents. All 23 patients had inducible sustained ventricular tachyarrhythmias (18 had uniform morphology sustained ventricular tachycardia (VT) and 5 had ventricular fibrillation [VF]) during control electrophysiologic study, and therapy had failed with a type IA agent and mexiletine alone. The combination therapy of mexiletine and the type IA agent prevented induction of any ventricular tachyarrhythmias in 8 of 23 patients. In 15 patients, the combination significantly prolonged the tachycardia cycle length and reduced the symptoms associated with the induced arrhythmia. Patients more likely to respond to the combination had shorter cycle lengths and polymorphic configuration of the control-induced arrhythmia. The increased efficacy of the combination therapy could not be attributed to higher plasma drug levels for the combination, as there was no significant difference in plasma levels for each drug when given alone or in combination. Thus, the increased efficacy most likely reflects a synergistic electropharmacologic effect of the 2 agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Antiarrhythmic drug efficacy for ventricular tachyarrhythmias associated with coronary artery disease as assessed by electrophysiologic studies.

The efficacy and proarrhythmic potential of antiarrhythmic agents were evaluated. Programmed ventricular stimulation was performed in 160 consecutive patients with coronary artery disease during a baseline study and 432 subsequent drug studies. The tachyarrhythmias induced during baseline studies were sustained ventricular tachycardia (121 patients), ventricular fibrillation (16 patients), and symptomatic nonsustained ventricular tachycardia (23 patients). Regimens were completely successful if fewer than 6 repetitive ventricular responses were inducible during therapy and partially successful if no more than 15 repetitive ventricular responses were inducible. Procainamide and quinidine were the most successful single agents, with overall success rates of 24% and 35%, respectively. Either procainamide or quinidine combined with mexiletine was the most successful combination (overall success of 23%). Each anti-arrhythmic regimen showed a proarrhythmic potential. The incidence of proarrhythmic effects ranged from 4 to 13%, with no significant difference between regimens. In 13% of patients at least 1 regimen produced a proarrhythmic effect. Patients treated with an antiarrhythmic regimen that prevented induction of arrhythmia had significantly fewer arrhythmia recurrences than patients treated with a regimen that failed to prevent it. In conclusion, identification of an effective drug regimen is possible in 38% of patients with lethal ventricular arrhythmias, proarrhythmic effects occur in a significant number of patients during electrophysiologic testing of antiarrhythmic regimens, and the clinical outcome in patients in whom ventricular arrhythmias are not inducible with ventricular stimulation have a better prognosis than those in whom arrhythmias continue to be inducible on therapy.

Adult↗
PubMed1985

Ventricular activation in normal sinus rhythm: abnormalities with recurrent sustained tachycardia and a history of myocardial infarction.

Left ventricular activation was studied in 21 patients: 7 with normal electrocardiograms (group I), 7 with prior transmural myocardial infarction (group II) and 7 with prior transmural myocardial infarction (MI) and recurrent sustained ventricular tachycardia (VT) (group III). Fragmented electrograms were defined as those less than 3 mV in amplitude and longer than 60 ms in duration. Such electrograms were found in no group I patients, 6 of 7 group II patients and all 7 group III patients. An average of 2 of the 12 sites mapped in each patient displayed fragmented electrograms in group II; an average of 6 of the 12 sites displayed fragmented electrograms in group III (p less than 0.01). Twelve of the 84 total sites mapped in group II displayed fragmented electrograms, whereas 39 of the 84 sites mapped in group III patients did (p less than 0.01). The longest fragmented electrogram found in the 6 group II patients in whom such electrograms were found was shorter in duration than the longest electrogram found in each of the 7 group III patients with fragmented electrograms (76 ms vs 135 ms, p less than 0.005). The duration of endocardial activation was longer in group II patients (79 +/- 7 ms) than in group I patients (39 +/- 4 ms, p less than 0.001). Duration of activation was also longer in group III patients (151 +/- 12 ms) than in either of the other groups (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography↗