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Biomedical subjects

B Lown

Publications and source records attributed to B Lown.

At least 37 records · Page 2Linked to original sources
PubMed1991

Behavioral arousal enhances inducibility and rate of ventricular tachycardia.

Behavioral arousal may trigger malignant cardiac arrhythmias. To study the effect of arousal on ventricular tachycardia, pigs were instrumented with catheters to measure mean arterial pressure and sample plasma catecholamines and left anterior descending coronary artery snares for occlusion 1 wk later. Bipolar pacing catheters were placed in the right ventricular apex to induce ventricular tachycardia. One week after occlusion, electrophysiological testing was repeated before and immediately after arousal caused either by restraining and lifting the pig in a canvas sling or by bringing a stall mate into the room. The number of stimuli needed to induce monomorphic ventricular tachycardia was reduced by both types of arousal (P less than 0.05) compared with control conditions. Ventricular tachycardia rate was increased 60 +/- 17 beats/min after lifting stimulation (P less than 0.05). When beta 1-receptor blockade was induced by metoprolol, inducibility of ventricular tachycardia and rate were not different from control. Thus, in pigs, arousal may facilitate arrhythmogenesis. This effect may be mediated by sympathetic neural activity in the heart because it was annulled by beta 1-adrenergic blockade.

Animals↗
PubMed1990

Assessment of the hemodynamic response to acetyl-strophanthidin by Doppler echocardiography in normal subjects and in those with coronary artery disease or idiopathic dilated cardiomyopathy.

The effect of acetyl-strophanthidin, a rapidly acting digitalis-like drug, was measured on peak flow velocity, stroke distance (an index of stroke volume) and minute distance (an index of cardiac output), determined by Doppler echocardiography in 21 subjects with a wide range of left ventricular ejection fractions (12 to 89%, average 47%). For the total study group, peak flow velocity increased from 99 +/- 10 to 110 +/- 13 cm/s (p less than 0.01), and stroke distance increased from 15.1 +/- 3.2 to 16.8 +/- 3.1 cm (p less than 0.01). Minute distance remained unchanged: 1,093 +/- 168 cm before and 1,129 +/- 187 cm after acetyl-strophanthidin (difference not significant). Improvement in Doppler parameters of forward blood flow was significantly (p less than 0.001) greater in subjects with left ventricular ejection fractions less than 60% (+17% for peak flow velocity, +22% for stroke distance and +15% for minute distance) than those with left ventricular ejection fractions greater than or equal to 60% (+4% for peak flow velocity, +2% for stroke distance and -8% for minute distance). These data suggest that Doppler echocardiography is a useful method to assess the efficacy of acute digitalis administration in improving forward blood flow.

Blood Flow Velocity↗
PubMed1990

Changes in cardiac output determined by continuous-wave Doppler echocardiography during propafenone or mexiletine drug testing.

Antiarrhythmic drugs may induce congestive heart failure in patients with malignant ventricular arrhythmias and depressed left ventricular (LV) function. Whether Doppler echocardiography can detect drug-induced depression in LV function was assessed. Continuous-wave Doppler measurements of ascending aortic blood flow velocity were obtained in 16 patients while not receiving antiarrhythmic drugs on 2 consecutive days to assess day-to-day variability, as well as while receiving maximally tolerated oral doses of mexiletine (11 patients) and propafenone (9 patients). While receiving propafenone, a drug with moderate negative inotropic activity, peak flow velocity declined by 9 +/- 8% (p less than 0.05), the flow velocity integral (termed stroke distance, representing stroke volume) declined by 8 +/- 11% (p less than 0.10), the rate-corrected stroke distance declined by 9 +/- 8% (p less than 0.02) and the minute distance, representing cardiac output, declined by 10 +/- 12% (p less than 0.05). In contrast, while receiving mexiletine, a drug with minimal negative inotropic activity, none of these parameters changed significantly. Five of 9 patients (56%) treated with propafenone showed a decline in rate-corrected stroke distance exceeding the 95% confidence limit of day-to-day variability, which was +/- 13 percent. Two of these 5 patients developed clinical signs of congestive heart failure. Continuous-wave Doppler echocardiography can detect antiarrhythmic drug-induced LV dysfunction and may be used to anticipate the development of significant clinically overt congestive heart failure.

Cardiac Output↗
PubMed1990

Epinephrine-induced decrease in repetitive extrasystole threshold is reversed by tyrosine in conscious dogs.

Previous studies indicate that availability of L-tyrosine, the precursor for catecholaminergic neurotransmitters, reduced psychological and physiological effects of stressful situations including hypotension, cold and behavioral stress. The current study examined the effect of L-tyrosine administration on cardiac vulnerability to arrhythmia induced by an infusion of epinephrine in conscious dogs. Heart rate, mean arterial pressure and cardiac electrophysiologic parameters, i.e., effective refractory period and repetitive extrasystole threshold, were measured during infusion of epinephrine (0.3 micrograms/kg/min x 30 min), before and after L-tyrosine (B mg/kg iv bolus). Epinephrine administration significantly increased heart rate by 39% (p less than 0.05), and decreased repetitive extrasystole threshold by 33% (p less than 0.05). Mean arterial pressure and effective refractory period were unchanged. Following L-tyrosine, repetitive extrasystole threshold was restored to baseline levels. Tyrosine may thus ameliorate stress-induced increases in ventricular vulnerability to arrhythmias in conscious animals.

Animals↗
PubMed1990

Inducible monomorphic sustained ventricular tachycardia in the conscious pig.

Sustained monomorphic ventricular tachycardia (VT) is of clinical importance but has not been readily modeled in conscious animals. Eleven pigs had myocardial infarction induced by pulling snares previously placed around the left anterior descending (LAD) coronary artery. Six days after occlusion, bipolar pacing catheters were inserted in the right ventricular apex for induction of VT. Testing was repeated in conscious pigs on 6 out of 8 to 19 days after infarction. Monomorphic VT was induced in each animal during each session, using three to four extrastimuli. VT was terminated by burst pacing in 74% of trials; average VT rate was 362 +/- 26 beats/min. VT was prevented in four of eight animals by procainamide and in five of eight animals by magnesium, but was not prevented by lidocaine or metoprolol. The model may be useful in the study of potentially malignant ventricular tachyarrhythmias, important prodromes for sudden death.

Animals↗
PubMed1990

Changes in ventricular fibrillation threshold during the development of perinephritic hypertension.

Established hypertension is associated with enhanced susceptibility to life-threatening arrhythmias. However, little is known about the effects of the development of hypertension on the electro-physiological properties of the heart. To study this relationship, dogs were chronically instrumented for recording mean arterial pressure and conducting cardiac electrical testing during right ventricular pacing using an intracavitary bipolar catheter. In normotension, ventricular fibrillation threshold was determined under alpha-chloralose anesthesia, after which perinephritic hypertension was induced by wrapping one kidney in silk followed by contralateral nephrectomy. During serial testing of the same animals, ventricular fibrillation threshold was significantly increased early in the development of hypertension (2 to 3 weeks after renal wrapping), but found to be significantly reduced at 6 to 7 weeks after renal wrapping. The increase in ventricular fibrillation threshold was eliminated by cholinergic blockade.

Animals↗
PubMed1990

The Mikamo lecture. Role of higher nervous activity in sudden cardiac death.

The brain receives and catalogues myriads of information from within and without the organism. These inputs promote neural integration of bodily function through a multiplicity of cybernetic feedback loops. Higher nervous activity shapes the contours of perceived well-being and determines the course and progress of disease. Behavioral and neural factors play an important role in cardiovascular function and are especially relevant to the problem of sudden cardiac death (SCD). Clinical data attesting to the role of biobehavioral factors in SCD derive from a diversity of sources. It has long been known that bereavement increases the prevalence of cardiac fatality. Business failure rates are strongly related to increased mortality among persons aged 55 and over. Recession in economic activity, with increasing unemployment, is associated with augmented death rates from ischemic heart disease. In extensive surveys conducted among London civil servants, Rose and Marmot found not only the level but the type of employment to be a factor determining coronary heart disease mortality. Blue collar workers had a 3.6 times greater chance of dying from heart disease than an age-matched population in the higher ranks of civil service. A man's employment status was a stronger predictor of risk for dying from coronary heart disease than any of the usual risk factors, such as smoking, blood pressure, height-weight ratio, leisure time activities, glucose tolerance, or plasma cholesterol. Operation of behavioral factors is also suggested by the time of occurrence of sudden death. Among 3,983 men followed for more than 30 years, Rabkin and co-workers observed an excess proportion of fatalities on Mondays. No such pattern was noted for cancer mortality. Not only the day of the week but the time of day appears to be a factor. Muller and co-workers found a significant preponderance in the occurrence of myocardial infarction and sudden death from 6:00 AM to noon. They could not implicate operation of circadian rhythm, but suggested a role for augmented autonomic neural discharge associated with early morning activities following waking from sleep. The longitudinal epidemiologic studies of the Health Insurance Plan of New York (HIP) have indicated an important association between behavioral and psychologic factors and the prevalence of sudden cardiac death.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Is amiodarone good for heartburn?

Three cases are reported in which resolution of severe esophagitic dyspepsia followed amiodarone therapy for cardiac arrhythmias. This effect has proved long lasting. The mechanism of amiodarone action may be related to its calcium antagonist or nitratelike properties that reduce lower esophageal sphincter tone. An alternate hypothesis calls attention to structural similarities between amiodarone and the histamine antagonist ranitidine, and suggests a previously unrecognized action of amiodarone on histamine receptors.

Aged↗
PubMed1989

Congestive heart failure induced by six of the newer antiarrhythmic drugs.

The incidence of drug-induced congestive heart failure with several newer antiarrhythmic agents including encainide, ethmozine, lorcainide, mexiletine, propafenone and tocainide was determined in a group of 407 patients who underwent 1,133 drug tests. The incidence rate ranged from 0.7% with lorcainide to 4.7% with propafenone. Congestive heart failure was present in 167 patients (41%) who underwent 491 drug trials. Congestive failure was induced in 15 (9%) of these 167 patients and involved 19 (3.9%) of the 491 tests. Left ventricular ejection fraction was 20 +/- 8% in patients who developed congestive failure, in contrast to 39 +/- 19% in those who did not (p less than 0.001). It is concluded that each of the six antiarrhythmic drugs examined has the potential to aggravate congestive heart failure in patients with reduced left ventricular ejection fraction or a history of congestive heart failure, but the incidence rate is low and its occurrence unpredictable.

Adolescent↗
PubMed1989

Reproducibility of exercise-induced ventricular arrhythmia in patients undergoing evaluation for malignant ventricular arrhythmia.

In patients with malignant ventricular arrhythmia, the utility of exercise testing for exposing arrhythmias and guiding antiarrhythmic drug selection and dosage is not yet generally accepted. A major reservation relates to the issue of reproducibility of arrhythmia provocation. This prospective study comprised 28 patients referred for evaluation of ventricular arrhythmia. In half of these subjects the clinical arrhythmia was sustained ventricular tachycardia or ventricular fibrillation. Maximal exercise testing adhering to a Bruce protocol was performed on 2 separate days. No antiarrhythmic drugs were administered at the time of testing. Of the 28 patients, 27 had an increase in arrhythmia with exercise. The prevalence rates of arrhythmia were greater than 80% and did not significantly differ between test 1 and test 2. Excluding infrequent single ventricular premature complexes, the reproducibility of a test with positive outcome was 76%. Similarly, test-retest agreement, a bidirectional measure of reproducibility, was greater than 74%. Kappa coefficients ranged from 0.26 to 0.36 for all grades of arrhythmia, indicating that reproducibility was consistently greater than by chance alone. Linear regression analysis of arrhythmia frequency in the 2 tests yielded R values of 0.76 to 0.96 and slopes of 0.82 to 1.2. No patient had enough spontaneous variability in repetitive forms to suggest spurious efficacy or aggravation. For ventricular premature complexes there was an 8 to 14% incidence of spurious efficacy and a 4 to 7% incidence of spurious aggravation. These results suggest that exercise-induced ventricular arrhythmia is sufficiently reproducible to serve as an adjunct method in the evaluation and management of patients with potentially life-threatening ventricular arrhythmias.

Adult↗
PubMed1989

Encainide and flecainide: are they interchangeable?

Encainide and flecainide are two recently released class IC antiarrhythmic agents that have been reported to be highly effective for suppressing all forms of ventricular arrhythmias. Both drugs are potent blockers of the sodium channel and produce marked slowing of conduction within the His-Purkinje system and myocardium. To establish if the response to one agent predicts the response to the other, the antiarrhythmic effect of the two drugs was compared in a group of 18 patients with malignant ventricular arrhythmia. Fourteen patients had sustained ventricular tachycardia and four patients had ventricular fibrillation. The average ejection fraction of this group was 37%. All patients had a high density of spontaneous ventricular arrhythmia and were evaluated noninvasively. Both drugs significantly reduced all forms of spontaneous arrhythmia. By Holter monitoring criteria, the effect of the two drugs was concordant in 61% (p = NS). By exercise criteria, the concordance rate was 50% (p = NS). Overall, 12 patients (67%) responded to encainide and eight (44%) patients responded to flecainide (p = NS). Only 10 of 18 (56%) patients had the same response to both agents (p = NS). There was no significant difference in ejection fraction or in average daily dose of drug between responders and nonresponders. Thus despite their similar electrophysiologic profile, the clinical antiarrhythmic effect of these two agents was different. For the noninvasive management of patients the response to one agent should not be used to predict the response to the other.

Adolescent↗
PubMed1989

Biventricular function during postextrasystolic potentiation in man. A study using list-mode radionuclide ventriculography.

The effects of postextrasystolic potentiation during spontaneous ventricular ectopy on both left and right ventricular function were studied in 12 patients with the aid of list-mode radionuclide ventriculography. The left ventricular ejection fraction showed a significant increase (+ 11.0 +/- 5.0%; p less than .001) with associated mild increases in end-diastolic volumes (+ 4.9 +/- 4.6; p less than .01) and significant decreases in end-systolic volumes (-13.4% +/- 7.3%; p less than .001). A more heterogeneous response was seen for the right ventricle. Right ventricular ejection increased significantly in 8/12 patients (+ 3.3 +/- 3.0%; p less than .02). Despite a large increase in end-diastolic volumes (+ 10 +/- 7.9%; p less than .001), there were only mild changes in end-systolic volumes (+ 2.2 +/- 9.0; p = NS). It is concluded that, for spontaneous ventricular ectopy in man, the increase in right ventricular ejection fraction reflects improved ventricular filling whereas the increase in left ventricular ejection fraction is linked to improved emptying.

Adult↗
PubMed1989

The effect of caffeine on ventricular ectopic activity in patients with malignant ventricular arrhythmia.

We evaluated the effect of caffeine on ventricular ectopic activity in a group of 50 consecutive patients with malignant ventricular arrhythmia. The clinical arrhythmia in these patients (mean age, 61 years) was recurrent ventricular tachycardia in 21 (42%), ventricular fibrillation in three (6%), and symptomatic nonsustained ventricular tachycardia in 26 (52%). Forty-two (84%) had either ischemic heart disease or cardiomyopathy. Each patient underwent two short-term drug trials on successive days, receiving either decaffeinated coffee mixed with 200 mg of caffeine or the decaffeinated drink alone. Continuous electrocardiographic recordings were made during the 30-minute control period, the three-hour observation period, and the hourly bicycle exercise tests. Forty-five patients (90%) exhibited ventricular couplets and 29 patients (58%) had salvos of ventricular tachycardia during the testing. However, no differences between the caffeine and decaffeinated trials were observed in either individual or group data on total or repetitive ventricular arrhythmia. Serum catecholamine levels reflected the average increase in serum caffeine level but were not associated with enhanced arrhythmia. We found no evidence that a modest dose of caffeine is arrhythmogenic, even among patients with known life-threatening arrhythmia.

Caffeine↗
PubMed1988

Combination antiarrhythmic therapy for management of malignant ventricular arrhythmia.

The efficacy of combination drug therapy in the suppression of ambient ventricular arrhythmia was retrospectively evaluated in a study of 49 patients discharged from the hospital taking 2 membrane-active antiarrhythmic agents. Thirty-one patients (63%) had ischemic heart disease, 15 had miscellaneous cardiac disorders and 3 were free of ostensible heart disease. Therapy in all patients had previously been unsuccessful with an average of 3.7 single membrane-active drugs. Antiarrhythmic agents were discontinued for at least 48 hours to determine baseline arrhythmia levels by Holter monitoring and maximal exercise treadmill testing. Ventricular premature beats were evaluated according to the grading system of Lown and Wolf. Data on ventricular ectopic activity were obtained during Holter monitoring and exercise testing for both a control ("drug-free") period and for a period of combination therapy. During the control period, ventricular tachycardia was recorded during 23% of monitored hours, and the level was nearly twofold greater during stress testing. After institution of combined therapy, the percent of monitored hours of arrhythmia were reduced during Holter monitoring, with a greater reduction in couplets and ventricular tachycardia than in single ventricular premature beats. Ventricular tachycardia was more difficult to provoke by exercise testing in patients taking combination therapy than in control subjects. These data indicate that combination therapy can significantly reduce the density of ventricular ectopic activity in patients refractory to monotherapy. During an average follow-up of 26 months, 23 patients (47%) were able to receive decreased drug dosages, affording diminished adverse effects and improved tolerance to long-term use.

Anti-Arrhythmia Agents↗
PubMed1988

Noninvasive evaluation of indecainide for serious ventricular tachyarrhythmia.

Indecainide, a new class 1C agent, was administered to 16 patients with a history of ventricular fibrillation or ventricular tachycardia. Evaluation of drug effect consisted of acute testing with 125 mg followed by a period of maintenance therapy. Efficacy, as evaluated with both ambulatory monitoring and exercise testing, was defined as total elimination of runs of ventricular tachycardia, greater than 90% reduction in couplets and greater than 50% decrease in ventricular premature complex. During acute drug testing 9 of the 16 patients responded to the drug. Four patients did not receive maintenance therapy with indecainide, because of toxic side effects. Of the remaining 12 patients, 7 responded to indecainide based on monitoring, 5 responded judged by exercise testing and 4 when both monitoring and exercise testing were considered. There was no correlation between dose, blood level of drug and effect on arrhythmia. In this small group acute drug testing did not appear to predict the response to the drug during maintenance therapy. Neurologic side effects were reported by 5 patients. Aggravation of arrhythmia occurred in 5 patients, 3 of whom had this complication during acute drug testing and 2 during maintenance therapy. Left ventricular ejection fraction, measured before and during therapy, decreased from an average of 43% to 35% (p less than 0.005). A reduction was observed irrespective of baseline left ventricular function. Indecainide is an effective antiarrhythmic agent in a small number of highly selected patients with serious ventricular arrhythmia, but potentially serious side effects limit its usefulness.

Adult↗
PubMed1988

Determinants of survival in patients with malignant ventricular arrhythmia associated with coronary artery disease.

The long-term survival data in patients with coronary artery disease and a history of malignant ventricular arrhythmia, defined as noninfarction ventricular fibrillation (VF) or hemodynamically compromising ventricular tachycardia (VT) followed for up to 9 years, were analyzed. In this group of 161 patients there was a total of 57 deaths, of which 35 (63%) were sudden. Life-table analysis demonstrated a 10% sudden death rate for all patients in the first year and a 7% annual rate in the subsequent 4 years. In patients managed noninvasively, the overall mortality rate was 27% over 9 years, or 3% per year. Suppression of ventricular tachycardia on both ambulatory monitoring and exercise testing was associated with improved survival. In patients evaluated by electrophysiologic testing the sudden death rate was 1.4% per year over an average of 5 years. This survival rate was not different compared with the noninvasive group (p = 0.09). Measures of left ventricular dysfunction and the frequency of ventricular arrhythmia before and after drug therapy were associated with a risk of sudden cardiac death by univariate analysis. Multivariate regression analysis identified 4 variables as independent predictors of sudden cardiac death: rales (p = 0.009), the number of runs of VT during exercise testing while receiving antiarrhythmic drug therapy (p = 0.0003), a history of congestive heart failure (p = 0.0009) and the number of premature beats on Holter monitoring (p = 0.01). These findings support the concept that suppression of repetitive arrhythmia on Holter monitor and exercise testing is a marker for improved survival among patients with malignant ventricular arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1988

Clinical predictors of arrhythmia worsening by antiarrhythmic drugs.

Aggravation of ventricular arrhythmia is a serious, potentially lethal, side effect that can occur with all antiarrhythmic agents. The purpose of this retrospective case-controlled study was to identify clinically useful parameters that would predict aggravation of arrhythmia. Patients in whom arrhythmia worsened while taking either quinidine, mexiletine or encainide were selected and matched to 2 similar patients who never developed this drug complication with any antiarrhythmic tested. A number of hemodynamic, electrophysiologic and pharmacologic parameters were compared. Only the presenting arrhythmia and a left ventricular ejection fraction less than 35% identified patients at risk for drug-induced aggravation of arrhythmia. Patients who presented with either sustained ventricular tachycardia or ventricular fibrillation were 3.4 times more likely to have arrhythmia aggravation compared with patients presenting with nonsustained ventricular tachycardia or ventricular premature beats. Patients with a left ventricular ejection fraction less than 35% were 2.2 times more likely to develop this drug complication compared with patients with an ejection fraction greater than 35%. There was no association between other clinical parameters, electrocardiographic intervals, ventricular arrhythmia density, drug dose or drug levels and aggravation of arrhythmia. In addition, drug aggravation to 1 drug did not predict its occurrence with another drug of the same class. Patients with a history of a sustained ventricular arrhythmia, especially when left ventricular dysfunction is present, are at high risk for the development of aggravation of arrhythmia.

Anilides↗