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Biomedical subjects

B Lown

Publications and source records attributed to B Lown.

At least 73 records · Page 4Linked to original sources
PubMed1987

Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat.

Brain serotoninergic neurons are known to participate in cardiovascular regulation. Administration of the serotonin precursor 5-l-hydroxytryptophan in conjunction with the monamine oxidase inhibitor phenelzine and the selective peripheral l-amino acid decarboxylase inhibitor carbidopa has been shown to raise the repetitive extrasystole threshold in the canine heart. The present investigation demonstrates that this drug regimen increases the cerebrospinal fluid concentration of serotonin and its major metabolite, 5-hydroxyindoleacetic acid, by 330 and 830%, respectively. By contrast, cerebrospinal fluid concentrations of norepinephrine and its major brain metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate, and of dopamine's metabolite, 3, 4-dihydroxyphenylacetic acid, were not significantly altered. Concomitantly, the ventricular fibrillation threshold was elevated by 42% and the effective refractory period prolonged by 7%. Efferent sympathetic neural activity was suppressed in the normal heart (from 7.9 +/- 1.3 to 3.9 +/- 1.1 impulses/s). The surge in sympathetic activity associated with acute myocardial ischemia was markedly attenuated. These results indicate that enhancement of central serotoninergic neurotransmission can reduce the susceptibility to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Delayed myocardial ischemia induced by anger.

The objectives of this study were to develop a reproducible behavioral model that simulates the anger state and to characterize its influence on myocardial blood flow in both the normal and compromised coronary circulations. Fourteen mongrel dogs of both sexes were studied. The animals were instrumented for the recording of electrocardiogram, arterial blood pressure, and left circumflex coronary arterial blood flow. A critical level of coronary stenosis was achieved with an adjustable occluder placed just distal to the flow probe. Anger was induced in the instrumented animals by having another dog challenge their access to food. In the absence of coronary artery stenosis, provocation of anger increased heart rate from 107 +/- 6 to 215 +/- 15 beats/min, arterial blood pressure from 95 +/- 4 to 142 +/- 5 mm Hg, and coronary blood flow from 31 +/- 5 to 72 +/- 9 ml/min. These variables returned to the preanger levels within 2 to 4 min. Induction of anger was repeated after a critical stenosis was applied to the left circumflex coronary artery. Anger increased heart rate from 112 +/- 6 to 210 +/- 16 beats/min, arterial blood pressure from 99 +/- 3 to 142 +/- 6 mm Hg, and coronary arterial flow from 23 +/- 5 to 35 +/- 7 ml/min. Within 2 to 4 min after the bout of anger, all dogs exhibited significant reductions in coronary arterial flow (35% of baseline; p less than .001), increases in coronary vascular resistance (557% of baseline; p less than .002), and ischemic ST segment changes in leads II, III, and aVF.(ABSTRACT TRUNCATED AT 250 WORDS)

Anger↗
PubMed1987

Signal averaging technique for noninvasive recording of late potentials in patients with coronary artery disease.

An advanced non invasive signal averaging technique was used to detect late potentials in two groups of patients: Group A (24 patients) with coronary artery disease (CAD) and without sustained ventricular tachycardia (VT) and Group B (8 patients) with CAD and sustained VT. Recorded analog data were digitized and aligned using a cross correlation function with fast Fourier transform schema, averaged and band pass filtered between 60 and 200 Hz with a non-recursive digital filter. Averaged filtered waveforms were analyzed by computer program for 3 parameters: (1) filtered QRS (fQRS) duration (2) interval between the peak of the R wave peak and the end of fQRS (R-LP) (3) RMS value of last 40 msec of fQRS (RMS). Significant change was found between Groups A and B in fQRS (101 -/+ 13 msec vs 123 -/+ 15 msec; p < .0005) and in R-LP vs 52 -/+ 11 msec vs 71-/+18 msec, p <.002). We conclude that (1) the use of a cross correlation triggering method and non-recursive digital filter enables a reliable recording of late potentials from the body surface; (2) fQRS and R-LP durations are sensitive indicators of CAD patients susceptible to VT.

Algorithms↗
PubMed1987

Sudden cardiac death: biobehavioral perspective.

Increasing evidence indicates that sudden death resulting from ventricular fibrillation may be triggered in some patients by behavioral and neural factors. In animal preparations, diverse psychologic stressors and augmented sympathetic neural traffic to the heart lower the vulnerable period threshold for ventricular fibrillation. Epidemiologic studies have demonstrated increased cardiac fatality after bereavement and unemployment, as it relates to social class and cultural dislocation, and as a function of level of education, psychologic stress, and social isolation. Ventricular premature beats (VPBs), which may be risk indicators of susceptibility to sudden death, are not affected by perturbations of the peripheral autonomic nervous system. However, differing psychologic stressors increase, whereas their abatement diminishes, VPB frequency and grade. The most potent stressors relate to the recall of emotionally charged experiences. Such stressors are uniquely individual and cannot be readily replicated. Among the most significant factors to reduce VPBs are non-rapid eye movement sleep and increases in vagal neural activity. Psychological precipitants are demonstrable in about 20% of patients experiencing malignant ventricular arrhythmias. A promising new avenue for investigation relates to the role of various central neurotransmitters and their dietary precursors in cardiac neural traffic. Augmenting central serotonin by administering its tryptophan precursor reduces sympathetic neural activity and protects the heart against ventricular fibrillation.

Animals↗
PubMed1986

Safety and efficacy of encainide for malignant ventricular arrhythmias.

The antiarrhythmic effect of encainide was evaluated in 140 patients with documented symptomatic ventricular tachycardia or ventricular fibrillation refractory to conventional agents. In 102 patients with reproducible spontaneous arrhythmia, noninvasive methods, including ambulatory monitoring and exercise testing, were used to evaluate drug efficacy, while in the remaining 38 patients electrophysiologic testing was performed. Side effects necessitated drug discontinuation in 10 patients before noninvasive evaluation. Of the remaining 92 patients 44 (48%) responded to encainide. Of the 38 patients who underwent electrophysiologic study, 1 discontinued encainide because of side effects and in 4 patients the spontaneous occurrence of sustained ventricular tachycardia precluded repeat study. Of the remaining 33 patients, 10 (30%) were rendered noninducible with encainide. The drug was more effective in those with a left ventricular ejection fraction greater than 35% (p less than 0.03) and in those presenting with nonsustained ventricular tachycardia. Side effects were reported in 53 of 140 patients (38%) and were primarily nausea, vomiting, headaches and tremors. Aggravation of arrhythmia occurred in 4% of patients with a history of nonsustained arrhythmia and in 25% of those with a history of sustained ventricular tachycardia or ventricular fibrillation. Worsening of arrhythmia was not related to mean dose of drug, mean blood level or electrocardiographic changes; it was more likely to occur in patients with a markedly reduced left ventricular ejection fraction (average 32%) and in those with a history of sustained ventricular tachyarrhythmia (p less than 0.05). Long-term encainide therapy was continued in 48 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Recurrence of malignant ventricular arrhythmia after antiarrhythmic drug withdrawal.

Selection of an antiarrhythmic drug program by noninvasive means for patients with malignant ventricular arrhythmia has not been demonstrated to be the decisive factor in promoting enhanced long-term survival. Twenty-four patients (16 men, mean age 56 years) with a history of either recurrent ventricular tachycardia or non-infarction ventricular fibrillation were studied after antiarrhythmic therapy had been discontinued. All patients had been symptom-free on a tailored drug program for a mean of 31 months. Twenty of the 24 patients were hospitalized and underwent systematic drug withdrawal to assess continued need for therapy or because of intolerable side effects. In 4 patients, medication was discontinued either on their own or by their local physician. Recurrence after drug withdrawal was defined as either recurrence of the presenting arrhythmia (ventricular tachycardia or ventricular fibrillation) (12 patients) or reappearance of repetitive arrhythmia during Holter monitoring or exercise stress testing comparable to pretreatment levels (11 patients). The clinical arrhythmia recurred in 12 patients. Nine patients had a cardiac arrest. These data document the high recurrence rate of malignant ventricular arrhythmia on cessation of a proved antiarrhythmic program. They further support the concept that patients with life-threatening arrhythmia can be protected from recurrence by noninvasive methods of drug selection that are guided by suppression of advanced forms of ventricular premature complexes.

Adult↗
PubMed1986

Daily reproducibility of electrophysiologic test results in malignant ventricular arrhythmia.

The reproducibility of electrophysiologic testing on successive days was assessed in the absence of antiarrhythmic drug treatment. Forty-two patients, 17 with compromising ventricular tachycardia and 25 with ventricular fibrillation unrelated to myocardial infarction, underwent 2 baseline studies. During the first electrophysiologic study, arrhythmia was induced in 32 of 42 patients (76%); however, during the second study a similar endpoint was reached in only 22 patients (52%) (chi 2 = 5.12, p less than 0.05). Only 18 of the 32 patients (56%) with induced arrhythmia during the first study had a reproducible result. Reproducibility was not related to presence of coronary artery disease, nature of presenting arrhythmia, or endpoint achieved (sustained or nonsustained ventricular tachycardia) during electrophysiologic study. Hence, reproducibility of endpoint during electrophysiologic investigation should be ascertained in each patient before initiating serial drug studies.

Adolescent↗
PubMed1986

Relationship between ease of inducibility of arrhythmia with electrophysiologic testing and response to antiarrhythmic therapy.

Electrophysiologic studies are an important tool for guiding the selection of an effective antiarrhythmic drug. The purpose of this study was to determine if there was a relationship between the number of extrastimuli necessary to induce arrhythmia and the response to antiarrhythmic drugs. A group of 56 patients with sustained ventricular tachycardia or ventricular fibrillation who were inducible underwent 235 single-drug studies (4.2 per patient). During the control study, one extrastimulus provoked an end point in 12 patients (group 1) and in only two patients (17%) was at least one drug effective. Of the 18 patients requiring two extrastimuli for induction during baseline (group 2), at least one drug was effective in 11 patients (61%). At least one drug was effective in 20 of 26 patients (77%) who required three extrastimuli (group 3). There were no significant differences among the three groups with respect to presenting arrhythmia, presence of coronary artery disease, or left ventricular ejection fraction. When single drugs or a combination of drugs were used, 58% of group 1, 72% of group 2, and 85% of group 3 were rendered noninducible. During a follow-up of 28 to 32 months, yearly recurrence of arrhythmia was 9.4%, 4.6%, and 1.7%, for the three groups, respectively.

Anti-Arrhythmia Agents↗
PubMed1986

The role of beta blocking agents as adjunct therapy to membrane stabilizing drugs in malignant ventricular arrhythmia.

Antiarrhythmic drugs are often either partially or totally ineffective for the suppression of ventricular arrhythmias in a given patient. Drug combinations afford an additional therapeutic option. We report the role of beta-blocking agents as adjunct therapy to membrane stabilizing drugs in the management of patients with malignant ventricular arrhythmias. The study group included 54 patients who were evaluated by 24-hour ambulatory monitoring and symptom-limited exercise testing. Patients underwent control studies without antiarrhythmic drugs, were evaluated on membrane stabilizing drugs and beta blocking agents separately, and were then tested on combination therapy. The combination of a beta-blocking agent and a membrane stabilizing drug abolished ventricular tachycardia and couplets in 83% and 86% of exercise tests in patients with this arrhythmia present during therapy with membrane drugs alone (p less than 0.01). The addition of a beta blocker to a membrane drug, as evaluated by ambulatory monitoring, resulted in an abolition of ventricular tachycardia and couplets in 43% and 20% of studies (p less than 0.05). Ventricular premature beat frequency was reduced by more than 50% in 65% of exercise tests and in 52% of monitoring studies (p less than 0.05). In this population, beta-blocking agents failed to reduce ventricular arrhythmias when used alone. Thus the addition of a beta blocker to a membrane stabilizing drug significantly enhances the suppression of ventricular arrhythmia, especially when assessed by exercise testing. This results from synergistic drug effects of the combination rather than from the effect of the individual drugs.

Adrenergic beta-Antagonists↗
PubMed1986

Protective effect of tiapamil against ventricular fibrillation during coronary artery occlusion.

Calcium channel antagonists differ in their effects on myocardial excitable properties. This study examines whether tiapamil (100 micrograms/kg/min intravenously) is capable of reducing the susceptibility to ventricular fibrillation (VF) during acute occlusion and reperfusion of the left anterior descending coronary artery. During occlusion, tiapamil elevated the VF threshold to 17.5 +/- 8.2 mA compared to a control of 8.6 +/- 5.9 mA (2p less than 0.01). However, no significant effect was noted upon reperfusion of the vessel. Adrenergic stimulation with norepinephrine, 0.5 microgram/kg/min, lowered the VF threshold by 32% (2p less than 0.02), and by 6% (N.S.) when tiapamil was infused concurrently. Thus, tiapamil protects the heart against VF during coronary occlusion, but not during reperfusion. This appears to be mediated in part by an antiadrenergic action of the drug.

Animals↗
PubMed1986

Effect of hypokalemia on susceptibility to ventricular fibrillation in the normal and ischemic canine heart.

To examine the impact of hypokalemia on cardiac electrical stability, the thresholds for repetitive extrasystole and ventricular fibrillation were determined before and after potassium depletion in 15 chloralose-anesthetized dogs. A reduction in serum potassium concentration from 3.6 to 2.1 mEq/L induced by hemodialysis decreased the repetitive extrasystole threshold by 30% and the ventricular fibrillation threshold by 25% (p less than 0.01). The increase in ventricular vulnerability following acute coronary occlusion was markedly augmented by concomitant potassium depletion. Thus, hypokalemia enhances the propensity for ventricular fibrillation in the normal as well as in the ischemic canine heart. These findings shed light on clinical observations of enhanced susceptibility to life-threatening arrhythmias during acute myocardial ischemia in hypokalemic patients.

Animals↗
PubMed1986

Mexiletine and tocainide: does response to one predict response to the other?

Mexiletine and tocainide were administered to 79 patients to determine whether the response to one of these drugs would predict the effect of the other. In 57 patients, the two agents were evaluated noninvasively with monitoring and exercise testing, and efficacy was judged by the suppression of spontaneous ventricular arrhythmia. In the remaining 22 patients, electrophysiologic testing was performed and efficacy was defined as the inability to induce more than two repetitive ventricular premature beats. An equal number of patients responded to mexiletine and tocainide (38 versus 39%). However, in only 42 patients (53%) were the results concordant. There was no difference in concordance when the results were analyzed by method of drug evaluation, left ventricular ejection fraction or etiology of presenting arrhythmia. It is concluded that mexiletine and tocainide have different clinical effects and must be evaluated individually.

Adult↗
PubMed1986

Effects of adrenergic and muscarinic receptor stimulation on serum potassium concentrations and myocardial electrical stability.

The influence of adrenergic and muscarinic receptor activation on cardiac electrical stability and on serum potassium concentrations was studied in 23 anaesthetised dogs. The ventricular fibrillation threshold was assessed using the single stimulus technique. Adrenaline (1.0 microgram X kg-1 X min-1) caused a brief rise and a subsequent prolonged fall in serum potassium concentration, which was accompanied by a decline in ventricular fibrillation threshold when baroreceptor activation was prevented. After pretreatment with the beta1 adrenoceptor blocking agent metoprolol (0.5 mg X kg-1), adrenaline did not alter vulnerability to ventricular fibrillation but still elicited hypokalaemia. In contrast, selective beta2 adrenoceptor blockade (ICI 118551, 100 micrograms X kg-1) prevented the adrenaline induced lowering of serum potassium concentration but not of ventricular vulnerability. Muscarinic receptor activation by methacholine (3.0 micrograms X kg-1 X min-1) had no effect on serum potassium concentration but increased the ventricular fibrillation threshold by 30%. When methacholine was administered concomitantly with adrenaline the decline in serum potassium concentration persisted, but the increase in ventricular vulnerability was completely prevented. It is concluded that in the normal canine myocardium adrenaline produces an increase in vulnerability that is mediated through beta 1 adrenoceptors and that the beta 2 adrenoceptor mediated hypokalaemia is dissociated from electrophysiological effects of adrenaline. Parasympathetic nervous system activation does not influence serum potassium concentrations but opposes the effects of adrenaline on susceptibility to ventricular fibrillation.

Adrenergic beta-Antagonists↗