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Biomedical subjects

B Lown

Publications and source records attributed to B Lown.

At least 109 records · Page 6Linked to original sources
PubMed1984

Effects of acetyl-strophanthidin on left ventricular function and ventricular arrhythmias.

Digitalis drugs can suppress ventricular arrhythmias. It is uncertain whether this effect results from improved left ventricular (LV) function. We utilized radionuclide scanning techniques to evaluate changes in LV ejection fraction (EF) after an infusion of acetyl-strophanthidin in 43 patients with frequent ventricular premature beats (VPBs) (44 to 2400/hr). Acetyl-strophanthidin suppressed ventricular arrhythmia in 17 patients, but LVEF increased in only six of these patients (57% to 67%), while it was unaltered in 11 patients (28% to 30%). In 26 patients ventricular arrhythmia was not suppressed. Fifteen of these patients had an increase in LVEF (60% vs 71%), while this was unchanged in 11 patients (27% vs 29%). Thus no correlation was observed between the positive inotropic and antiarrhythmic action of acetyl-strophanthidin on ventricular arrhythmia and LVEF. We conclude that the suppression of VPBs by acetyl-strophanthidin is independent of the drug's effects on LV function. Evidence is reviewed suggesting that the antiarrhythmic effect of acetyl-strophanthidin on ventricular ectopic activity is due to its vagotonic action.

Adult↗
PubMed1984

Lorcainide in patients with refractory ventricular tachyarrhythmia.

Lorcainide, a new antiarrhythmic agent with local anesthetic or membrane-stabilizing properties similar to those of quinidine, was tested in 76 patients with diverse types of heart disease and recurrent ventricular tachycardia or ventricular fibrillation. Lorcainide was administered for 72 to 96 hours in a dose ranging from 200 to 400 mg daily. Evaluation of drug efficacy involved ambulatory monitoring and exercise stress testing in 60 patients who had high grade ventricular arrhythmia. Invasive electrophysiologic testing was carried out in the remaining 16 patients who exhibited infrequent ventricular ectopic activity during control studies. Lorcainide was effective in 21 (38%) of 56 patients evaluated for suppression of ventricular ectopic activity and in 6 (40%) of 15 who had invasive testing. In five patients, the drug was discontinued because of toxic reactions. Thus, 27 (38%) of the 71 patients who completed the drug study responded to lorcainide. Side effects, reported by 42 patients (55.3%), consisted primarily of insomnia and gastrointestinal symptoms; 7 experienced aggravation of arrhythmia. Fifteen patients were discharged while receiving lorcainide therapy, but in four the treatment was discontinued after 2 months because of side effects. Three patients died, one suddenly. It is concluded that lorcainide is of value in a small subset of patients with life-threatening ventricular arrhythmias who have proven refractory to conventional drugs. Its usefulness is limited by the high frequency of insomnia.

Adolescent↗
PubMed1984

Propafenone: a new agent for ventricular arrhythmia.

Propafenone, a new antiarrhythmic agent, was utilized in 30 patients with diverse heart disease who presented with sustained hemodynamically unstable ventricular arrhythmia. Drug efficacy was judged by means of ambulatory electrocardiographic monitoring and exercise testing. Nine patients additionally had invasive electrophysiologic studies. Seventeen patients (57%) responded to therapy as judged by monitoring and 21 patients (70%) responded to therapy as judged by exercise testing. When both methods were considered, 16 patients (53%) responded. The acute drug test predicted the result of maintenance therapy in 91% of patients. Seven of nine patients who had electrophysiologic testing responded based on this technique, and in all cases the results were concordant with the noninvasive evaluation. Serum blood levels did not correlate with antiarrhythmic effect. In patients with myocardial impairment, echocardiographic assessment of left ventricular function indicated a decrease in ejection fraction during propafenone therapy (32 versus 24%, p less than 0.05), while no change was observed in patients with normal left ventricular function. Side effects occurred in nine patients and included exacerbation of congestive heart failure, development of conduction abnormalities and aggravation of arrhythmia, each occurring in two patients. Ten patients who continued on long-term propafenone therapy for an average of 10 months (range 3 to 13) have remained free of arrhythmia and side effects. Propafenone needs to be employed with caution in patients with congestive heart failure or evidence of conduction system disease.

Adolescent↗
PubMed1984

Safety of maximal exercise testing in patients at high risk for ventricular arrhythmia.

While maximal exercise testing is useful for detection of arrhythmias and assessment of antiarrhythmic drug efficacy, few reports have documented the safety of this procedure in patients with malignant ventricular arrhythmias. We reviewed the complications of symptom-limited exercise in 263 patients with such arrhythmias who underwent a total of 1377 maximal treadmill tests. Seventy-four percent of the population studied had a history of ventricular fibrillation or hemodynamically compromising ventricular tachycardia and the remainder had experienced ventricular tachycardia in the setting of either recent myocardial infarction or poor left ventricular function. A complication was defined as the occurrence of arrhythmia during exercise testing--ventricular fibrillation, ventricular tachycardia, or bradycardia--that mandated immediate medical treatment (cardioversion, use of intravenous drugs, or closed-chest compression). Complications were noted in 24 patients (9.1%) during 32 tests (2.3%), whereas 239 patients (90.9%) were free of complication during 1345 tests (97.7%). There were no deaths, myocardial infarctions, or lasting morbid events. Clinical descriptors associated with complications included male sex, presence of coronary artery disease, and a history of exertional arrhythmia (p less than .05). Clinical variables previously considered to confer increased risk during exercise, such as poor left ventricular function, high-grade ventricular arrhythmias (Lown grade 4A or 4B) before or during exercise, exertional hypotension, and ST depression, were not predictive of complications (p greater than .05). Occurrence of a complication was also unaffected by the use of antiarrhythmic drugs at the time of exercise (chi square = 0.19, p greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Efficacy of amiodarone for refractory supraventricular tachyarrhythmias.

Amiodarone was administered to 121 patients (82 males, 39 females; average age 59 years) with refractory atrial tachyarrhythmias. All patients had experienced recurrent atrial fibrillation, atrial flutter, or reentrant supraventricular tachycardia previously refractory to digitalis drugs, beta-adrenergic blocking agents, and an array of membrance-active preparations. Seventy-four of 121 patients (61.2%) had no evidence of organic heart disease, whereas 17 patients experienced arrhythmia as a result of coronary heart disease, nine had preexcitation syndromes, 16 had primary valvular heart disease, and five patients, had congenital heart disease. Atrial fibrillation alone or in combination with atrial flutter was the primary dysrhythmia in 95 of 121 patients (78.5%), whereas in 26 patients (21.5%) supraventricular tachycardia was the primary refractory dysrhythmia. Fifty-one patients (42%) had experienced tachyarrhythmias for more than 10 years prior to the use of amiodarone. During an average follow-up of 27.3 months, complete suppression of atrial arrhythmias occurred in 98 of 121 patients (81%), and partial suppression occurred in seven (5.8%). In 16 patients (13.2%) the drug was deemed ineffective, and in eight patients (6.6%) amiodarone was discontinued because of intolerable side effects. The average blood serum concentration among successfully treated patients was 1.9 micrograms/ml, whereas the average concentration for those with side effects was 2.3 micrograms/ml. Thus, amiodarone is an extremely effective (greater than 85%) agent for refractory atrial tachyarrhythmias. Once daily administration, generally tolerable side effects, and excellent patient tolerance render this agent an attractive option for the management of these dysrhythmias.

Adolescent↗
PubMed1983

The repetitive extrasystole as an index of vulnerability to ventricular fibrillation during myocardial ischemia in the canine heart.

The repetitive extrasystole threshold (RET) is a reliable measure of vulnerability to ventricular fibrillation (VF) during diverse interventions in the normal heart. Whether this relationship also holds during varying degrees of myocardial ischemia has not been adequately explored. In 15 chloralose-anesthetized dogs, circumflex coronary blood flow (CBF) was decreased progressively with the use of an externally applied balloon occluder. There was a statistically significant correlation between the RET and ventricular fibrillation threshold (VFT) until left circumflex coronary artery flow was reduced by 90% of control values (r = 0.92). During reductions of CBF of 90% or greater, the VFT fell more than the RET and the RET/VFT ratio was disrupted. Total coronary occlusion, whether performed abruptly or gradually (5 minutes), likewise resulted in a disproportionate decline in VFT. During sustained total coronary occlusion, the VFT recovered to control values within 15 minutes, and the relationship between the RE and VF thresholds was restored. We conclude that the vulnerable period threshold for provoking repetitive extrasystole is a reliable index of vulnerability to VF during myocardial ischemia and remains so until nearly total occlusion of a major coronary vessel.

Animals↗
PubMed1983

Effect of alpha-adrenergic receptor stimulation on ventricular electrical properties in the normal canine heart.

We examined the effects of alpha-adrenergic stimulation on ventricular excitability, refractoriness, and vulnerability to fibrillation. Methoxamine or phenylephrine was infused in five dogs each before and after aortic arch and carotid sinus baroreceptor denervation, in doses which increased mean arterial blood pressure by 20 to 30 mm Hg. Methoxamine or phenylephrine caused an increase in the ventricular fibrillation threshold (VFT) (from 27% to 41%) and in the repetitive extrasystole threshold (RET) (from 28% to 39%). This effect was abolished by baroreceptor denervation. Neither drug altered mid-diastolic threshold or effective refractory period duration either before or after denervation. We conclude that alpha-receptor activation exerts no direct effect on ventricular excitability or refractoriness in the normal intact heart.

Animals↗
PubMed1983

Relationship between sympathetic neural activity, coronary dynamics, and vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion.

The relationship between neural sympathetic discharge and vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion was studied in 26 chloralose-anesthetized dogs. Preganglionic cardiac sympathetic impulse activity and ventricular fibrillation thresholds were separately determined before and during a 10-minute period of left anterior descending coronary artery occlusion and during release-reperfusion. Within 2 minutes of occlusion the ventricular fibrillation threshold was significantly decreased (from 25 +/- 1.3 to 16 +/- 2.3 mA, p less than 0.05) corresponding with the period of maximal activation of cardiac sympathetic preganglionic fibers (from 4.4 +/- 0.2 to 6.3 +/- 0.5 impulses/sec). Coronary sinus blood flow and oxygen tension decreased significantly. All these changes persisted for 5 to 6 minutes, thereafter returning to control levels despite continued obstruction of the coronary artery. A transient but significant reduction in ventricular fibrillation threshold also occurred with release of the occlusion but was unaccompanied by increases in sympathetic neural discharge. Bilateral stellectomy completely prevented the ventricular fibrillation threshold changes observed during coronary artery occlusion. However, there was no change in coronary sinus oxygen tension or blood flow. During reperfusion, stellectomy increased rather than decreased vulnerability to ventricular fibrillation. Stellectomy augmented the reactive hyperemic response to release-reperfusion. These findings indicate that enhanced cardiac sympathetic neural activity contributes to ventricular vulnerability associated with coronary artery obstruction. An opposite action results during release-reperfusion. Cardiac sympathetic neural discharge, by reducing the magnitude of reactive hyperemic response through influence on coronary vascular tone, exerts an antifibrillatory effect.

Animals↗
PubMed1983

Use of nonsustained ventricular tachycardia as a guide to antiarrhythmic drug therapy in patients with malignant ventricular arrhythmia.

From a population of 260 patients with malignant ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia with syncope) we identified 52 (20%) who had infrequent ventricular premature beats during exercise testing and 48 hours of ambulatory monitoring. These patients underwent invasive electrophysiologic study utilizing programmed premature stimulation with up to three extrastimuli at currents of twice and three times middiastolic threshold. The end point for testing was nonsustained ventricular tachycardia (NSVT), defined as 3 to 20 propagated responses resulting from the last premature stimulus. A multiple response was obtained in 45 patients consisting of reproducible NSVT in 36 and sustained ventricular tachycardia in nine. The 36 patients with NSVT underwent 540 electrophysiologic tests with 18 antiarrhythmic agents. Suppression of the repetitive response was achieved in 31 of the 36 patients (86.1%). After an average follow-up of 21 months, one of 31 patients in whom the repetitive response had been abolished had recurrent arrhythmia. This contrasted with recurrence in two of the five patients in whom NSVT was still provoked. During the extensive testing, ventricular fibrillation was not induced. Sustained ventricular tachycardia occurred in 27 of the 540 tests (5.0%), but cardioversion was required in only 12 (2.2%). We conclude that NSVT constitutes a safe electrophysiologic end point for selecting an effective antiarrhythmic program in patients who have experienced malignant ventricular arrhythmia but in whom monitoring and exercise testing are inadequate to guide therapy.

Adolescent↗
PubMed1983

Programmed electrical stimulation of the heart in coronary artery disease.

The induction of ventricular arrhythmia in patients with a history of malignant ventricular arrhythmia by programmed electrical stimulation (PES) is associated with a poor prognosis. However, the incidence and significance of inducible arrhythmia in patients with stable coronary artery disease (CAD) who do not have a history of serious arrhythmia are unknown. We studied 32 such patients (31 men, mean age 55 years) with PES at the time of cardiac catheterization. Fourteen patients (Group I) manifested greater than or equal to 3 extraventricular responses when challenged with 1 to 3 propagated right ventricular extrastimuli during ventricular pacing. Twelve (86%) of these 14 had evidence of left ventricular dysfunction (LVD), defined by a global ejection fraction of less than 50% or regional wall motion abnormalities. The remaining 18 patients (Group II) manifested less than or equal to 2 responses to extrastimulation. Only 4 (22%) of these 18 had LVD. Proximal 3-vessel CAD was more frequent in Group I patients (10 of 14, 71%) than in Group II (7 of 18, 39%). Only 5 patients (4 from Group I and 1 from Group II) demonstrated complex arrhythmia during exercise testing or ambulatory monitoring. The induction of extraventricular responses during PES may serve as an independent marker of electrical instability in the coronary population and is a much more common finding in those with LVD.

Aged↗
PubMed1983

Influence of intracoronary platelet aggregation on ventricular electrical properties during partial coronary artery stenosis.

Several clinical studies suggest that drugs which interfere with platelet function may protect persons at risk for sudden death. However, there is no direct evidence that intracoronary platelet aggregation produces cardiac arrhythmias. Induction of fixed partial coronary stenoses in dogs resulted in spontaneous cyclical reductions in coronary blood flow of 21 to 81% (p less than 0.01). These changes are known to be associated with the formation and distal embolization of platelet aggregates. These reductions in coronary blood flow were accompanied by significant decreases in the repetitive extrasystole (-40%) and ventricular fibrillation (-38%) thresholds. Prostacyclin (PGI2), a potent vasodilator and inhibitor of platelet activation, in increasing doses of from 25 to 100 ng/kg/min caused a stepwise decrease in the frequency and magnitude of coronary blood flow fluctuations and restored the vulnerable period thresholds to control levels. Indomethacin (5 mg/kg), an inhibitor of cyclo-oxygenase activation and platelet thromboxane A2 production, produced similar results. The mechanism of coronary blood flow reduction appears to be mechanical blockade of the vessel lumen by platelet thrombi and production of myocardial ischemia. These results suggest that intracoronary platelet aggregation contributes to electrical destabilization of the myocardium and may predispose to ventricular fibrillation. A model is thus available for further investigating the role of platelets and antiplatelet drugs in modulating ventricular electrical stability.

Animals↗
PubMed1983

Intrinsic sympathomimetic activity and the effects of beta-adrenergic blocking drugs on vulnerability to ventricular fibrillation.

Beta-adrenergic blocking agents differ considerably in their effects on myocardial excitable properties. The possibility that intrinsic sympathomimetic activity might contribute to such differences has not been adequately explored. This study examined the influence of intrinsic sympathomimetic activity on the electrophysiologic effects of three agents with varying degrees of such activity. Intravenous propranolol (0.5 mg/kg), oxprenolol (0.5 mg/kg) and pindolol (0.05 mg/kg) were administered in 16 anesthetized dogs. The effects of the drugs on ventricular vulnerability were studied over a 2 hour period. Propranolol and oxprenolol raised the ventricular fibrillation threshold by 42 and 56%, respectively. In contrast, pindolol resulted in an elevation of only 25%. After depletion of endogenous norepinephrine stores using reserpine, pindolol led to a decrease of the ventricular fibrillation threshold, which was reversed by propranolol. These data indicate that intrinsic sympathomimetic activity of beta-adrenergic blocking agents substantially alters their ultimate effect on myocardial excitable properties.

Adrenergic beta-Antagonists↗
PubMed1983

Decreased vulnerability to ventricular fibrillation by vasodilator-induced baroreceptor sensitisation.

Vulnerability to ventricular fibrillation (VF) is affected by changes in systemic arterial blood pressure which are mediated through the sympathetic nervous system. We determined that small doses of a vasodilator drug can abolish the enhanced ventricular vulnerability induced by norepinephrine infusion. Noradrenaline (0.5 micrograms X kg-1 X min-1) caused a fall in ventricular fibrillation threshold from 30 to 20 mA (P less than 0.001). Pretreatment with prostaglandin E1, I2 or nitroglycerin at doses which reduced mean arterial blood pressure by 0.7 to 1.3 kPa (5 to 10 mmHg) abolished the enhanced vulnerability produced by noradrenaline. Following baroreceptor denervation, these agents no longer afforded protection against the profibrillatory action of noradrenaline. We conclude that small doses of vasodilator agents can augment ventricular electrical stability. The mechanism for this protective action appears to be a decrease in cardiac sympathetic tone resulting from vasodilatation of baroreceptor areas.

Alprostadil↗