Biomedical subjects

B Lown

Publications and source records attributed to B Lown.

At least 19 recordsLinked to original sources

PubMed1992

Results of a second-opinion trial among patients recommended for coronary angiography.

OBJECTIVE: To assess the feasibility of carrying out a second-opinion trial for patients urged to undergo coronary angiography and to assess the long-range outcome of such patients denied that procedure, and the criteria evolved for reaching such a conclusion. DESIGN: A case series of patients referred for a second opinion as to the need for coronary angiography. Patients were followed up by questionnaire, telephone call, and center visits. SETTING: Cardiovascular referral center and teaching hospital in Boston, Mass. PATIENTS: One hundred seventy-one patients with coronary artery disease (144 men, average age 60 years; range, 36 to 88 years). Three patients became unavailable for follow-up during a mean of 46.5 months. OUTCOME MEASURES: Concordant-discordant outcome as to the second opinion, cardiac events, invasive interventions, quality of life questionnaire, and level of symptoms. RESULTS: One hundred thirty-four (80%) of the 168 patients were judged not to require angiography; it was recommended in six. In 28 (16%) recommendation was deferred pending further studies. At a mean follow-up of 46.5 months among the 168 patients, there were seven cardiac deaths (annualized cardiac mortality of 1.1%); 19 patients experienced a new myocardial infarction (2.7% annualized rate), while 27 patients (4.3%) were judged to have developed unstable angina. Twenty-six patients (15.4%) ultimately underwent either coronary bypass or angioplasty. CONCLUSIONS: In a large fraction of medically stable patients with coronary disease who are urged to undergo coronary angiography, the procedure can be safely deferred. While there may be a limitation in terms of generalizing this experience to all patients with coronary disease, we reasonably conclude that an estimated 50% of coronary angiography currently being undertaken in the United States is unnecessary, or at least could be postponed.

Adult↗

PubMed1992

Transient coronary stenosis associated with arrhythmia and ischemia 24 hours after reperfusion.

We examined the electrophysiologic sequelae of transient reductions in coronary blood flow (CBF) in conscious dogs. Animals were instrumented to measure arterial pressure, heart rate, repetitive extrasystole threshold (RET), and CBF before coronary stenosis, during 90 minutes of a 50% reduction in CBF, and at 1, 24, 48, and 72 hours after reperfusion. RET was decreased at 24 and 48 hours but returned to baseline by 72 hours after reperfusion. Frequent ventricular ectopic activity (VEA), absent during the control period, was noted during stenosis and at 1, 24, and 48 hours after reperfusion. beta-Adrenergic blockade (metoprolol) normalized the decreased RET at 24 hours. Addition of alpha 1-adrenergic blockade (prazosin) abolished VEA. Endocardial blood flow in the posterior papillary muscle of the left ventricle was reduced by 52 +/- 9% during stenosis, was similar to baseline levels by 1 hour after reperfusion, and decreased by 39 +/- 5% at 24 hours. We conclude that episodes of modest coronary artery stenosis may be followed by electrophysiologic changes indicative of increased vulnerability to malignant ventricular arrhythmias.

Animals↗

PubMed1992

The prevalence of proarrhythmic events during moricizine therapy and their relationship to ventricular function.

The prevalence of proarrhythmic events during moricizine therapy was studied in 144 patients who were treated for symptomatic ventricular tachycardia or ventricular fibrillation. The overall incidence of proarrhythmia was 15.3%. (Twenty-two patients exhibited 23 events.) Ventricular fibrillation occurred in six patients (which led to three deaths), incessant ventricular tachycardia occurred in seven, and new sustained ventricular tachycardia in four. Patients with proarrhythmia had significantly lower left ventricular ejection fraction (24% vs 39%; p less than 0.0001), higher prevalence of congestive heart failure (68% vs 36%; p less than 0.005), and higher incidence of previous proarrhythmia (45% vs 9%; p less than 0.0001). No significant difference between the two groups was found in respect to age, arrhythmia at presentation, underlying heart disease, moricizine dose, or concomitant drug therapy.

Drug Evaluation↗

PubMed1992

Catecholamines in cerebrospinal fluid are increased by behavioral arousal and myocardial ischemia.

To study the central neural mechanisms involved in malignant ventricular arrhythmia, concentrations of norepinephrine in the cerebrospinal fluid were measured during behavioral stimulation and during coronary artery occlusion. Pigs were instrumented via thoracotomy with catheters to measure mean arterial pressure and plasma catecholamines and with silk snares around the left anterior descending coronary artery for occlusion after recovery from surgery. Cannulas were placed in the lateral ventricle of the brain to sample cerebrospinal fluid. Behavioral arousal was induced by lifting the pig in a canvas sling for 5 min. Mean arterial pressure, heart rate, and both plasma and cerebrospinal fluid norepinephrine concentrations increased significantly after lifting stimulation. In a separate experiment, 5 min after coronary artery occlusion, both plasma catecholamines and norepinephrine in cerebrospinal fluid were significantly elevated. Furthermore, pigs in which ventricular fibrillation occurred after occlusion had significantly higher concentrations of norepinephrine in cerebrospinal fluid before coronary artery occlusion.

Animals↗

PubMed1992

Control of ventricular fibrillation after coronary artery occlusion via intracerebroventricular injections.

The central nervous system (CNS) may play a larger role than previously thought in the development of ventricular fibrillation after coronary artery occlusion. The probability of ventricular fibrillation after complete, permanent occlusion of the left anterior descending coronary artery was 52% in conscious control pigs. After the administration into the lateral cerebral ventricle of tyrosine, the amino acid precursor of the catecholamine neurotransmitters, 100% of the animals developed ventricular fibrillation. After tyrosine plus propranolol, a beta-adrenoceptor antagonist, only 9% of pigs developed ventricular fibrillation. Treatment with propranolol alone did not affect the outcome. Catecholamine synthesis in the CNS may be associated with the development of ventricular fibrillation after coronary artery occlusion.

Animals↗

PubMed1991

Changes in left atrial size in patients with lone atrial fibrillation.

A retrospective analysis was performed on 23 subjects with lone atrial fibrillation who were followed for an average of 6.2 years (1.1-12.8 years). In all patients, underlying organic heart disease was excluded based on history, physical exam, electrocardiogram, echocardiogram, and Doppler ultrasound interrogation. All patients had at least two echocardiographic studies during the period of observation. Atrial fibrillation was chronic in 11 subjects and paroxysmal in 12. All echocardiographic measurements were obtained by averaging the measurements of two blinded investigators. Left atrial size increased an average of 5.6 mm which translates into a 14.7% increase over the baseline measurement. This increase in size was not associated with a change in left ventricular mass or fractional shortening as determined by echocardiography. Subjects with chronic atrial fibrillation had a larger percent increase than subjects with paroxysmal atrial fibrillation (18.9 vs. 10.8%), although this relative change in size failed to reach statistical significance. The only variable which significantly contributed to the change in left atrial size was the duration of follow-up. We conclude that atrial fibrillation occurring in patients with lone atrial fibrillation may cause a slow and progressive increase in left atrial size independent of changes in left ventricular size or function.

Aged↗

PubMed1991

Diazepam administered prior to coronary artery occlusion increases latency to ventricular fibrillation.

Few studies have addressed the antiarrhythmic potential of pretreatment with diazepam in acute myocardial infarction. Thus, the effect of diazepam pretreatment prior to coronary artery occlusion was examined in conscious pigs. Animals were instrumented with aortic catheters to measure arterial pressure, a pulmonary artery catheter for drug administration, and a snare around the left anterior descending coronary artery for permanent occlusion one week later. Diazepam (1 mg/kg iv bolus) or vehicle was administered 10 minutes prior to occlusion. Eight of 14 animals receiving diazepam (57%) and 13 of 22 receiving vehicle animals (59%) developed ventricular fibrillation following coronary occlusion. However, the latency to ventricular fibrillation was significantly shorter (7 +/- 1 min) in animals receiving vehicle compared to animals receiving diazepam (11 +/- 1 min). Significant increases in heart rate were seen up to 5 hours after coronary occlusion only in animals receiving vehicle. The results indicate that diazepam pretreatment can increase ventricular fibrillation latency and prevent heart rate increases following acute myocardial infarction.

Animals↗

PubMed1991

Decreases in repetitive extrasystole threshold in the conscious pig with myocardial infarct were reversed by tyrosine.

Reports indicate that the administration of tyrosine, the precursor amino acid for catecholaminergic neurotransmitters, may be beneficial under conditions of physiologic stress. We studied the effects of tyrosine on vulnerability to ventricular arrhythmia in conscious pigs with healing myocardial infarcts, and sham operated (intact) pigs. Mean arterial pressure and heart rate were measured via chronically implanted aortic catheters. The repetitive extrasystole threshold (defined as the energy in milliamperes (ma) needed to cause a spontaneous ventricular beat following a premature beat induced by an electrical impulse), was measured via a bipolar pacing catheter placed during instrumentation surgery in the apex of the right ventricle. One week after infarct, the myocardial infarct group was studied before and ninety minutes after the administration of tyrosine (8 mg/kg iv). Before tyrosine, the myocardial infarct group had a significantly lower repetitive extrasystole threshold (12 +/- 1 ma) compared to the intact group (19 +/- 2 ma). Ninety minutes after tyrosine, the repetitive extrasystole threshold in the myocardial infarct group was 17 +/- 1 ma. The availability of tyrosine did not alter the repetitive extrasystole threshold in the intact group. Thus, vulnerability to ventricular arrhythmia was enhanced in pigs with recent myocardial infarction. Tyrosine, which can be nutritionally manipulated, may reduce myocardial vulnerability to arrhythmia after infarct.

Animals↗

PubMed1991

Decrease in repetitive extrasystole threshold during epinephrine infusion is enhanced in conscious dogs with perinephritic hypertension.

Hypertension is associated with myocardial hypertrophy as well as increased adrenergic responsiveness, both of which can predispose to malignant ventricular arrhythmias. This study was designed to test the effects of subpressor doses of epinephrine (0.15 and 0.3 micrograms/kg/min x 30 min) on vulnerability to ventricular arrhythmia in normotensive and perinephritic hypertensive dogs. Two groups of 6 dogs each were chronically instrumented with aortic catheters to measure mean arterial pressure and bipolar pacing catheters in the apex of the right ventricle to measure repetitive extrasystole threshold, an index of vulnerability to ventricular fibrillation. In the normotensive dogs, the low dose of epinephrine (0.15 micrograms/kg/min IV) had no significant effects on mean arterial pressure, heart rate of repetitive extrasystole threshold. However, in the hypertensive dogs, the same dose caused a significant 39% increase in heart rate (p less than 0.05) and 41% decrease in repetitive extrasystole threshold (p less than 0.05). These findings suggest that electrophysiological vulnerability of the myocardium caused by epinephrine infusion is enhanced in the hypertensive animal.

Animals↗

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↗