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Biomedical subjects

B Lown

Publications and source records attributed to B Lown.

At least 55 records · Page 3Linked to original sources
PubMed1988

The effect of intracoronary lidocaine infusion on acetylstrophanthidin-induced ventricular arrhythmia in dogs.

Antiarrhythmic drugs frequently cause extracardiac side effects that limit their use. If intracoronary delivery of a lower dose of drug to an electrically unstable focus can control arrhythmias, systemic adverse effects of these agents might be avoided. We investigated whether intracoronary lidocaine can suppress ventricular arrhythmia induced by acetylstrophanthidin, a rapidly acting digitalislike agent. We isolated and then cannulated either the left anterior descending or the left circumflex coronary artery in 12 pentobarbital-anesthetized dogs. Sustained ventricular tachycardia that persisted for 11.4 +/- 8.6 minutes was reliably induced by the intracoronary infusion. In all of 24 trials, an intracoronary lidocaine bolus at 2% of the usual systemic dose (0.77 mg/30 sec) abolished digitalis-induced ventricular tachycardia for an average of 2.0 +/- 1.8 minutes. This effect was not observed after a saline bolus. We conclude that an intracoronary bolus of low-dose lidocaine can suppress acetylstrophanthidin-induced ventricular arrhythmia.

Animals↗
PubMed1988

The effect of intracoronary lidocaine on ventricular arrhythmia in the infarcted canine heart.

The efficacy of intracoronary administration of lidocaine was studied in three groups of dogs with experimental myocardial infarction induced by occlusion of the left anterior descending coronary artery (LAD). Group 1 included 14 anesthetized and group 2, 7 conscious animals to which lidocaine 1.4 micrograms/kg/minute was administered as an intracoronary infusion. Group 3 consisted of 17 anesthetized dogs that received an intracoronary bolus of lidocaine 40 micrograms/kg over 30 seconds. In group 1, lidocaine reduced ventricular arrhythmia by 59 +/- 30% (p less than 0.001), whereas systemic lidocaine achieved a reduction by 61 +/- 37% (p 0.06). In seven dogs, lidocaine blood levels were measured in the great cardiac and femoral veins. At the end of the infusion the drug concentration was 3.4 +/- 2.2 micrograms/ml in the great cardiac and 1.3 +/- 1.1 micrograms/ml in the femoral vein (p less than 0.05). The reduction in ventricular arrhythmia correlated with the great cardiac vein lidocaine concentration (r = 0.70; p less than 0.05), but not with the drug level in the femoral vein (r = 0.06; NS). In group 2, lidocaine was ineffective by both routes of administration. This may have been related to higher sympathetic activity, as suggested by an elevated heart rate in conscious compared to anesthetized animals (186 +/- 6 vs 164 +/- 21 bpm; p 0.0054). In group 3, bolus injections of lidocaine into the LAD reduced ventricular arrhythmia by 66% (p 0.001). We conclude that by perfusing the infarcted zone with lidocaine, a significant antiarrhythmic effect can be achieved with 2% of the systemic dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Antifibrillatory action of the narcotic agonist fentanyl.

Morphine, an opiate alkaloid with mixed mu- and delta-agonist properties, raises the ventricular fibrillation threshold in anesthetized dogs by altering autonomic tone. To elucidate further underlying structure-activity relationships, the effect of fentanyl, a nonalkaloid, mu-selective agonist in wide clinical use, was studied. Fentanyl (30 micrograms/kg) was given intravenously to 27 chloralose-anesthetized dogs, and ventricular fibrillation threshold was measured by means of the single-stimulus technique. In the baseline state fentanyl raised the ventricular fibrillation threshold by 14%. When the dogs were subjected to hemorrhagic stress, this effect was amplified to 29% (p less than 0.0001). Bilateral cervical vagotomy abolished fentanyl's antifibrillatory effect, but neither atropine sulfate (0.4 mg/kg/hr) nor atropine methylnitrate (0.5 mg/kg/hr) did so. Fentanyl's influence on the fibrillation threshold during hemorrhage was significantly reduced by bilateral stellate ganglionectomy (p less than 0.005). It is concluded that fentanyl raises the ventricular fibrillation threshold by its known sympathoinhibitory action rather than by its vagal efferent activating effect. The facts that an intact vagus is required and that hemorrhage amplifies the effect suggest that the antifibrillatory effect of fentanyl is mediated through the afferent component of the baroreflex arc.

Animals↗
PubMed1988

Intravenous lorcainide for symptomatic ventricular tachyarrhythmias: comparison with lidocaine and oral lorcainide.

Intravenous lorcainide and lidocaine were administered to 25 patients with symptomatic ventricular tachyarrhythmias in a randomized single-blind crossover study. Prior to drug therapy, each patient underwent 48 hours of ambulatory monitoring and exercise testing on a motorized treadmill. At the completion of baseline studies, patients were randomized to receive either lidocaine or lorcainide intravenously. The dose of lidocaine was 1.0 mg/kg by bolus followed by an infusion of 2 to 3 mg/min. The dose of lorcainide was 2.0 mg/kg followed by a constant infusion of 200 to 300 mg over 24 hours. Two patients developed side effects on lidocaine and the infusion was discontinued prior to evaluation of efficacy. Of the remaining 23 patients, 11 (48%) had their arrhythmia controlled, defined as a greater than 90% reduction in repetitive forms (couplets and ventricular tachycardia) and a 50% reduction in ventricular premature beats. Lorcainide was effective in 8 of the 25 patients (32%). There was no correlation between the effect of lidocaine and the response to lorcainide (p = NS). Oral lorcainide therapy was administered to 17 patients who were free of side effects during the intravenous infusion. The oral drug was effective in nine patients (53%), five of whom had responded to the intravenous drug, and was ineffective in eight, seven of whom were also unresponsive to intravenous lorcainide. The intravenous drug predicted the response to the oral form in 71% of patients, but this was not statistically significant. Side effects occurred in 10 patients (59%) and were primarily neurologic.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Spontaneous variability and circadian distribution of ectopic activity in patients with malignant ventricular arrhythmia.

Day to day variability of ventricular ectopic activity was analyzed in 45 patients with a history of malignant ventricular tachyarrhythmias who underwent two successive 24 h periods of ambulatory electrocardiographic (ECG) monitoring in the absence of antiarrhythmic drugs; 26 were male and 19 female, with a mean age of 56 years (range 15 to 76). The total number of single ventricular premature beats, couplets and ventricular tachycardia beats and runs on days 1 and 2 demonstrated a consistent overall correlation (r = 0.76 to 0.84). Individual variability was evaluated by regression analysis with determination of 95% confidence limits. The minimal decrease in arrhythmia density necessary to distinguish true drug effect from spontaneous variability was 64% for single ventricular premature beats, 83% for couplets, 90% for ventricular tachycardia runs and 93% for ventricular tachycardia beats. To meet the criteria for arrhythmia aggravation, the arrhythmia density had to increase by 400, 877, 1,500 and 2,400%, respectively. Multivariate analysis disclosed an inverse relation between day to day arrhythmia variability and baseline arrhythmia density and age. Variability was more pronounced in patients with coronary artery disease but was not influenced by the type of presenting arrhythmia or left ventricular function. The diurnal distribution of arrhythmias and heart rate followed a distinct circadian pattern. These data indicate that, despite good group reproducibility, spontaneous arrhythmia variability in individuals is substantial, necessitating standards to define both drug effect and arrhythmia aggravation.

Adolescent↗
PubMed1987

Considerations of current methods for drug selection in treating malignant ventricular arrhythmias.

The current burgeoning interest in antiarrhythmic drugs derives in large measure from a growing concern with the enormous problem of sudden cardiac death. Until the latter half of the twentieth century, beyond a nodding acknowledgment of its massive prevalence, this syndrome received but scant attention from the medical profession. In the early 1960s a number of insights changed perceptions as well as practice. These related to 4 postulates: (1) sudden cardiac death, in the majority of victims, was due to ventricular tachyarrhythmias either initiated by or culminating rapidly in ventricular fibrillation; (2) the lethal arrhythmia was not the consequence of irreversible pathomorphologic impairment of the contractile apparatus, but rather the expression of an electrophysiologic derangement; (3) the triggering of ventricular fibrillation was the result of an electrical accident both reversible as well as preventable; (4) the potential victim was identifiable either by the presence of certain grades of ventricular ectopic activity or by exposure of repetitive ectopic activity or by exposure of repetitive ventricular arrhythmias by electrophysiologic techniques. The innovations that have led to these insights and their consequences have been numerous and continuous. Among these are direct current defibrillation, cardioversion, coronary care units, bystander-initiated cardiopulmonary resuscitation, ambulatory electrocardiographic monitoring and exercise stress testing for exposing ventricular arrhythmias, electrophysiologic provocative testing and mapping techniques, overdrive programmable pacemakers as well as implantable defibrillators and cardioverters, and surgical, electrical and laser techniques for ablating the nidus or interrupting the pathways of the arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1987

Ethmozine (moricizine HCl) therapy for complex ventricular arrhythmias.

Moricizine HCl (Ethmozine), a new antiarrhythmic agent, was administered to 102 patients with refractory ventricular fibrillation (n = 31), sustained ventricular tachycardia (VT) (n = 46) or symptomatic nonsustained VT (n = 25). A noninvasive approach utilizing monitoring and exercise testing was used in 82 patients who had a high density of reproducible spontaneous arrhythmia, whereas 20 patients without such arrhythmia required invasive electrophysiologic testing. The dosage of moricizine HCl was 200 mg 3 times daily, and during 5 to 6 days was titrated up to a maximum of 400 mg 3 times daily or 15 mg/kg daily, based on arrhythmia suppression and occurrence of side effects. Criteria for efficacy were a greater than 90% reduction in repetitive ventricular premature beats (couplets and runs of VT) and a greater than 50% reduction in ventricular premature beats when noninvasive methods were used. When electrophysiologic testing was used, the drug was judged effective if it prevented the induction of greater than 2 repetitive responses. Of 75 patients completing noninvasive study, 30 (40%) responded to moricizine HCl therapy, whereas only 1 of 20 patients undergoing electrophysiologic testing responded. There was no difference in moricizine HCl blood levels between responders and nonresponders (0.41 microgram/ml vs 0.43 microgram/ml, difference not significant). Side effects occurred in 28 patients (27%). Most frequent were aggravation of arrhythmia (n = 12), nausea and vomiting (n = 5), central nervous system toxicity (n = 3) and anticholinergic side effects (n = 3). The response rate to moricizine HCl therapy was higher in patients with nonsustained VT (62%) compared with those with sustained VT (19%) or ventricular fibrillation (33%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Effects of Ethmozine (moricizine HCl) on ventricular function using echocardiographic, hemodynamic and radionuclide assessments.

Ventricular arrhythmias combined with left ventricular (LV) dysfunction in patients portend a poor prognosis. Most antiarrhythmic agents have not been sufficiently investigated to adequately describe detrimental effects on LV function; we report the effects of moricizine HCl on ventricular function in 4 trials highlighting patients with LV dysfunction. Quantitative 2-dimensional echocardiography was used to evaluate 81 patients pre- and posttreatment. There was no change in mean global LV ejection fraction (EF) during placebo compared with moricizine HCl therapy (47 +/- 15% vs 46 +/- 14%, p greater than 0.05). In a separate trial, radionuclide LVEF at rest and exercise tolerance testing were performed in 24 patients with life-threatening ventricular arrhythmias who had a mean control LVEF of 40 +/- 19%. No significant change during moricizine HCl therapy (38 +/- 19%, p greater than 0.05) was detected and exercise parameters were unchanged. Rest and exercise LV function was measured during right-sided heart catheterization in a placebo-controlled study of 20 patients with ventricular tachycardia. Moricizine HCl was well tolerated without hemodynamic deterioration in all but 3 patients, who could be identified by their inability to increase stroke volume index during exercise. Finally, the relation between initial LV function and resultant antiarrhythmic efficacy indicates that moricizine HCl controls arrhythmias best in patients with LVEF greater than 30%.

Adult↗
PubMed1987

Results of a second-opinion program for coronary artery bypass graft surgery.

Second opinions for surgical procedures are now being sought by patients or are required by insurance carriers. We examined outcomes among 88 patients (76 men; average age, 59 years) referred for a second opinion as to the need for coronary artery bypass graft surgery. All patients had undergone coronary arteriography, which disclosed in 63 (72%) multivessel coronary artery disease, while in the remaining 25 patients single-vessel disease involved the left anterior descending coronary artery. Continuation of medical therapy was recommended for 74 (84%) of the 88 patients. Sixty of these 74 patients chose this option and continued to receive medical therapy without any fatalities during a follow-up period of 27.8 months. The remaining 14 patients elected to cross over to surgical therapy at an average of 11.3 months from the second opinion. We conclude that second opinions for selected, motivated patients slated for coronary artery bypass graft operation afford a significant and safe option. Moreover, a majority of patients will adhere to a second opinion recommending medical therapy, thus reducing the need for surgical intervention by as much as 50%. Since the study was based on a small sample size of self-selected patients, these data require caution in extrapolating to the general population with coronary artery disease.

Adult↗
PubMed1987

Aggravation of arrhythmia by antiarrhythmic drugs--incidence and predictors.

Aggravation of arrhythmia by antiarrhythmic drugs is a potentially serious complication. In over 1,287 noninvasive drug studies involving 11 antiarrhythmic drugs, arrhythmia aggravation occurred in 117 tests (9%). During 248 electrophysiologic tests, 45 cases (18%) of aggravation occurred. In an attempt to define predictors of this complication, 51 patients with aggravated arrhythmia were compared with 102 patients without this complication. Arrhythmia aggravation was not associated with age, sex, type or extent of heart disease, baseline electrocardiogram, drug-induced changes on electrocardiogram or density of baseline arrhythmia on monitoring or exercise testing. Aggravation with 1 drug did not predict occurrence with another drug of the same class. The only statistically important relation was the type of presenting arrhythmia. Patients with a history of a sustained tachyarrhythmia (ventricular tachycardia or ventricular fibrillation) had a risk of this complication that was 2.5 times greater than that of patients presenting with only nonsustained ventricular tachycardia or ventricular premature beats (p = 0.01). There was also a relation to the presence of left ventricular dysfunction (p = 0.04). For the most part, however, aggravation of arrhythmia is not predictable, and cautious use of antiarrhythmic drugs is essential.

Anti-Arrhythmia Agents↗
PubMed1987

Predictors of antiarrhythmic drug efficacy in patients with malignant ventricular tachyarrhythmias.

The relationship between arrhythmia density observed during ambulatory monitoring, left ventricular ejection fraction (EF), and response to antiarrhythmic drug therapy was evaluated in 94 patients presenting with ventricular fibrillation (VF) (n = 20) or ventricular tachycardia (VT) (n = 74). Following baseline studies, an average of 4.9 antiarrhythmic drugs were tested singly in each patient. Univariate and multivariate analyses revealed that the density of VT on baseline ambulatory monitoring and initial left ventricular EF were independent predictors of drug efficacy. The 45 patients with an EF less than or equal to 35% responded to 34 +/- 29% of drugs tested, whereas the 49 with an EF greater than 35% had arrhythmia suppression with 46 +/- 28% of agents (p less than 0.038). Patients exhibiting VT during greater than or equal to 50% of monitoring hours responded to 32 +/- 26% of drugs, whereas those with VT during less than 50% of hours showed arrhythmia suppression with 48 +/- 29% of antiarrhythmic agents tested (p = 0.009). During a mean follow-up period of 12.9 months, the annual sudden death mortality for all patients was 9.3%. However, 8 of the 55 patients responding to less than 50% of drugs tested died suddenly and 17 had recurrent VT. By contrast, only 1 of the 39 patients responding to greater than or equal to 50% of the antiarrhythmic drugs tested died suddenly and two experienced recurrent VT (p = 0.00005).(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗
PubMed1987

Influence of beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties and serum potassium concentration in the anesthetized dog.

The influence of selective beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties was studied in 18 anesthetized dogs. Selective beta 2-adrenoceptor activation by salbutamol failed to alter myocardia excitability but significantly lowered serum potassium concentration. Excitability, refractoriness, and ventricular fibrillation threshold were also not changed after administration of 100 and 200 micrograms/kg of the selective beta 2-antagonist ICI 118,551. However, at a dose of 500 micrograms/kg, refractoriness was prolonged and ventricular fibrillation threshold increased. These changes appear to be due to blockade of beta 1-adrenoceptors rather than to membrane stabilizing effects, since in catecholamine-depleted animals even the highest dose of ICI 118,551 did not alter myocardial electrical properties. It is concluded that beta 2-adrenoceptors do not influence electrophysiologic properties of the canine myocardium.

Adrenergic beta-Agonists↗