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Biomedical subjects

L B Mitchell

Publications and source records attributed to L B Mitchell.

At least 73 records · Page 4Linked to original sources
PubMed1991

Reduction in defibrillator shocks with an implantable device combining antitachycardia pacing and shock therapy.

Implantable defibrillators reduce the risk of sudden death in patients with malignant ventricular arrhythmias, but significant restriction in quality of life can occur as a result of frequent device activation. To determine if a device that provides both antitachycardia pacing and shock therapy can safely reduce the frequency of shocks after implantation, 46 consecutive patients undergoing initial implantation of a defibrillator were studied. In all patients, the implanted device provided antitachycardia pacing and shock therapy. Detected tachycardia characteristics and the results of therapy were stored in the device's memory. There were 42 men and 4 women, aged 26 to 71 years (mean 58.7 +/- 13.5). Left ventricular ejection fraction ranged from 13% to 67% (mean 32.2 +/- 13.4%) and 31 patients had experienced one or more episodes of cardiac arrest. Induced arrhythmias included sustained monomorphic ventricular tachycardia in 38 patients, nonsustained polymorphic ventricular tachycardia in 2 and ventricular fibrillation in 4. Over a total follow-up period of 255 patient-months (range 1 to 13, mean 6.1), 25 patients experienced spontaneous arrhythmic events. In 22 patients, 909 episodes of tachycardia were treated by antitachycardia pacing, which was successful on 840 occasions (92.4%). Acceleration of ventricular tachycardia by pacing therapy was estimated to have occurred 39 times. Syncope occurred once during pacing-induced acceleration of ventricular tachycardia. Forty-four episodes of tachycardia in seven patients were treated directly by shocks because of short tachycardia cycle length; 88% of all detected tachycardias were treated without the need for shocks. Four patients died from cardiorespiratory failure and one patient died suddenly without any detected tachyarrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1991

Propafenone-induced torsade de pointes: cross-reactivity with quinidine.

A 77-year-old female with new onset atrial fibrillation occurring in the absence of structural heart disease developed torsade de pointes during therapy with quinidine bisulfate 500 mg orally every 8 hours. Ten days after quinidine therapy had been discontinued she developed torsade de pointes while receiving propafenone 300 mg orally every 8 hours. This case demonstrates that propafenone may be associated with torsade de pointes and suggests a cross-reactivity between this effect and prior occurrence of torsade de pointes on Class IA antiarrhythmic drug therapy.

Aged↗
PubMed1991

Mexiletine/quinidine combination therapy: electrophysiologic correlates of anti-arrhythmic efficacy.

This article reviews the data which support the use of selected drug combinations to enhance anti-arrhythmic activity. Specifically, we have focused on the mexiletine-quinidine interaction and the relation between anti-arrhythmic efficacy and electrophysiologic effects. In an initial clinical study, we found that combination therapy with mexiletine-quinidine produced enhanced efficacy in suppressing spontaneous ventricular tachycardia with fewer side-effects than high dose monotherapy. This enhanced efficacy has been confirmed in other laboratories. Combination therapy also enhanced suppression of inducible ventricular tachycardia in patients and in animal models. Animal models were used to assess the relation between electrophysiologic effects and anti-arrhythmic efficacy. In the animal studies, combination therapy produced selective prolongation of refractoriness and conduction in the infarct and peri-infarct zones without significant changes in the normal zone. Subsequent studies focused on the relative contribution of sodium channel and potassium channel blocking properties of these drugs to the enhanced activity seen with the combination. Studies using the selective sodium channel blocker tetrodotoxin confirmed that sodium channel blockade was necessary for this interaction. To assess the contribution of prolongation of action potential duration by quinidine to the combined effect we compared the anti-arrhythmic and electrophysiologic effects of the stereoisomers quinidine and quinine given alone and in combination with mexiletine. These experimental data confirm that the property of prolongation of action potential duration by quinidine is essential to the interaction. When comparing quinidine and quinine it is apparent that prolongation of refractoriness in the peri-infarct zone is essential for anti-arrhythmic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Melperone: electrophysiologic and antiarrhythmic activity in humans.

Previous studies in animals and in humans have shown that melperone, a neuroleptic butyrophenone, has class III electrophysiologic activity. However, its antiarrhythmic activity has not been assessed in humans. Accordingly, the electrophysiologic and antiarrhythmic effects of melperone were assessed in 23 patients with symptomatic ventricular tachyarrhythmias. Seventeen patients had electrophysiologic testing while receiving melperone. At oral daily dosages greater than or equal to 240 mg, melperone produced significant prolongations of QT intervals (385 +/- 11 vs. 355 +/- 22 ms, p less than 0.05), ventricular effective refractory periods (263 +/- 18 vs. 243 +/- 28 ms, p less than 0.05; 260 +/- 18 vs. 235 +/- 27 ms, p less than 0.01; and 243 +/- 23 vs. 222 +/- 28 ms, p less than 0.01; at 600-, 500-, and 400-ms pacing cycle lengths, respectively) and ventricular tachycardia (VT) cycle lengths (286 +/- 46 vs. 239 +/- 70 ms, p less than 0.05). Inducible VT was suppressed entirely in one patient. In three other patients, inducible sustained VT became nonsustained. No significant negative inotropic effects were observed. The majority of patients (70%) experienced some adverse effect, the commonest of which was neurologic. In conclusion, melperone had significant class III electrophysiologic and antiarrhythmic activity in humans. Its clinical use may be limited by the high incidence of adverse effects.

Adult↗
PubMed1989

Cardiac refractoriness. Age-dependence in normal subjects.

The effects of age on cardiac electrophysiologic measurements were assessed in 30 subjects between the ages of 18 and 73 years and free of structural heart disease. Occult heart disease was excluded by a normal treadmill exercise tolerance test, a rest and exercise radionuclide angiogram, and/or a cardiac catheterization. Effective and functional refractory periods of right atrium, right ventricle, and atrioventricular node were assessed. The relationship between these measurements and age was examined using linear regression. There were significant correlations between age and atrial effective and functional refractory periods, atrioventricular effective refractory period, and ventricular effective and functional refractory periods. Other electrophysiologic measures showed no such relationship with age.

Adult↗
PubMed1989

Contribution of quinidine metabolites to electrophysiologic responses in human subjects.

The quinidine metabolites 3-hydroxyquinidine, 2'-oxoquinidione, and quinidine-N-oxide and the contaminant dihydroquinidine have been shown to have electrophysiologic activity. This study investigated the time-dependent contributions of quinidine, dihydroquinidine, and the quinidine metabolites to the electrophysiologic effects of a prolonged quinidine infusion in 14 patients referred for management of symptomatic ventricular tachyarrhythmias. Electrophysiologic testing and blood sampling were done at baseline and every 5 minutes throughout a 110-minute quinidine infusion. Changes in ventricular effective refractory periods correlated significantly with serum concentrations of quinidine-N-oxide (r = 0.54; p less than 0.001), 3-hydroxyquinidine (r = 0.50; p less than 0.001), and time (r = 0.52; p less than 0.001) but did not correlate with the quinidine concentrations (r = 0.19). Multiple linear regression revealed that only 3-hydroxyquinidine and time contributed independently to changes in the ventricular effective refractory period. Quinidine concentration was the only variable that contributed independently to changes in ventricular tachycardiac cycle lengths. Time was the only variable that correlated independently with changes in QRS and QTc durations. These data indicate that active metabolites accumulate during an intravenous infusion that attains therapeutic quinidine levels and that quinidine and its metabolites may have different electrophysiologic effects.

Aged↗
PubMed1989

Concentration-response relationships of disopyramide in patients with ventricular tachycardia.

The protein binding of disopyramide is altered when concentration is increased within the therapeutic range. A wide range of free concentrations may be produced at a given total concentration. The present study assessed whether intracardiac electrophysiologic responses to disopyramide related better to free or to total concentration. Intravenous infusions of disopyramide were evaluated in 17 patients with inducible sustained ventricular tachycardia. The first maintenance infusion produced total serum concentrations of 11.7 +/- 2 mumols/L, and no significant increase occurred at higher-dose infusions. However, free concentrations during the first and second maintenance infusions were significantly different at 5.3 +/- 1 mumols/L and 6.8 +/- 1 mumols/L, respectively. Free fraction also increased significantly, from 45% +/- 8% to 50% +/- 7%. Overall change in QTc interval and ventricular tachycardia cycle length correlated with free concentration but not with total concentration. This study showed that some intracardiac measurements correlate with free concentration but that none correlate with total concentration.

Disopyramide↗
PubMed1989

Amiloride. Antiarrhythmic and electrophysiologic actions in patients with inducible sustained ventricular tachycardia.

This study assessed the antiarrhythmic activity of amiloride in 35 patients with inducible sustained ventricular tachycardia. Patients had failed to respond to 3.6 +/- 1.0 antiarrhythmic drugs. Ventricular tachycardia was reproducibly induced by programmed electrical stimulation in all patients at the baseline study. Amiloride was given at 10 and 20 mg/day p.o. on a twice-daily schedule that achieved serum concentrations of 21 +/- 17 and 36 +/- 18 ng/ml, respectively. The mean left ventricular ejection fraction was unchanged from 36 +/- 14% at baseline to 37 +/- 17% during amiloride treatment. Amiloride significantly increased serum potassium from 4.6 +/- 0.4 to 5.1 +/- 0.4 mM. Four patients failed amiloride therapy with spontaneous nonsustained ventricular tachycardia. The remaining 31 patients were assessed by repeat programmed stimulation. Six patients had complete antiarrhythmic response, and an additional six patients had less than 15 beats of ventricular tachycardia induced. Therefore, amiloride was an efficacious antiarrhythmic treatment in 12 of 35 (34%) patients. Amiloride concentrations were significantly higher (52 +/- 20 ng/ml) in patients that responded than in patients that did not respond (30 +/- 15 ng/ml). The only electrophysiologic measurement that changed significantly was the ventricular functional refractory period (from 269 +/- 24 to 283 +/- 25 msec, p less than 0.05). Amiloride also suppressed frequent, spontaneous ventricular premature beats in eight of 15 patients (53%). No somatic side effects occurred. Two of the five patients discharged on amiloride therapy developed asymptomatic nonsustained ventricular tachycardia, and this prompted a change in antiarrhythmic therapy. Both died suddenly of arrhythmia during substitute empiric antiarrhythmic drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Electropharmacology of amiodarone therapy initiation. Time courses of onset of electrophysiologic and antiarrhythmic effects.

The time courses of onset of the electrophysiologic and antiarrhythmic effects of amiodarone were determined with serial electrophysiologic studies in 34 patients with inducible ventricular tachycardia. A standardized oral loading dosage was used for all patients (1,200 mg/day for 14 days; 800 mg/day for 7 days; and 400 mg/day thereafter). Eleven patients had the studies performed at baseline and after 2, 6, 10, and 20 weeks. Subsequently, 23 patients had studies at baseline and after 2 and 10 weeks. Changes in atrial, sinus, and atrioventricular nodal properties and in conduction intervals were maximal within 2 weeks (early effects). For example, atrioventricular nodal Wenckebach cycle length increased between baseline (369 +/- 80 msec) and 2 weeks (498 +/- 78 msec) (p less than 0.001) but did not change further after 10 weeks (500 +/- 89 msec). However, ventricular Class III effects required 10 weeks to become maximal (late effects). For example, the QT interval during atrial pacing increased between baseline (355 +/- 36 msec) and 2 weeks (406 +/- 37 msec) (p less than 0.001) and increased further after 10 weeks (436 +/- 45 msec) (p less than 0.001). Antiarrhythmic effects also followed different time courses of onset. Suppression of ventricular premature beats was maximal within 2 weeks. However, suppression of ventricular tachycardia inducibility and slowing of ventricular tachycardia rate was not maximal for 10 weeks. Correlations between serum desethylamiodarone concentrations and some late effects suggest that the mechanism of the time delay to maximal ventricular Class III effects may involve desethylamiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Right and left ventricular function during chronic amiodarone therapy.

Although chronic therapy with amiodarone is an effective means of suppressing ventricular tachycardia, its long-term effects on ventricular function have not been evaluated. Therefore, left ventricular (LV) and right ventricular (RV) ejection fraction (EF) as well as wall motion score were assessed in 21 patients with ventricular tachycardia before therapy and after 2, 6, 10 and 20 weeks of amiodarone therapy. Serum amiodarone levels after 2, 6, 10 and 20 weeks were 1.9 +/- 0.7, 1.7 +/- 0.6, 1.5 +/- 0.6 and 1.5 +/- 0.7 micrograms/ml, respectively. Drug therapy did not significantly affect the mean LVEF (0 weeks 38 +/- 17, 2 weeks 40 +/- 17, 6 weeks 40 +/- 17, 10 weeks 41 +/- 18 and 20 weeks 40 +/- 18%) or the mean RVEF. Neither LV wall motion score nor RV wall motion score were changed significantly during amiodarone therapy. Fourteen patients had a drug-free LVEF less than 40% (mean 28 +/- 7%). Ventricular function in this subgroup was not impaired after 20 weeks of amiodarone therapy (drug-free LVEF 28 +/- 7%, 20 weeks LVEF 29 +/- 9%; drug-free RVEF 42 +/- 13%, 20 weeks RVEF 41 +/- 12%). Ten patients who were evaluated 34 +/- 6 months after initiation of amiodarone therapy had no significant change in LVEF (drug-free 37 +/- 20%, 34 months 43 +/- 20%). Ventricular functional reserve was assessed after 20 weeks of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Defective release of tissue plasminogen activator in patients with sickle cell anemia.

Recent studies suggest that intravascular coagulation occurs in sickle cell anemia. There is also some evidence that decreased fibrinolytic activity may be associated with the disorder. In the current study we measured tissue plasminogen activator levels (t-PA) in seven asymptomatic patients with sickle cell anemia. The mean level of releasable t-PA was only 0.01 IU/mL +/- 0.005 (SEM) as compared to 118 healthy volunteers with levels of 0.70 +/- 0.10 (SEM). Despite the small sample size, the difference between the two groups was statistically significant (P less than .001). These data suggest that defective release of t-PA may contribute to a hypercoagulable state in sickle cell anemia.

Anemia, Sickle Cell↗
PubMed1988

Effect of oral combination therapy with mexiletine and quinidine on left and right ventricular function.

Combination therapy with mexiletine (MEX) and quinidine (Q) may be more efficacious than monotherapy with either drug in suppressing ventricular arrhythmias, but its effects on ventricular performance are not known. Thus, right ventricular ejection fraction (RVEF) and left ventricular ejection fraction (LVEF) and wall motion score (WMS) were assessed in 14 patients with ventricular tachycardia before antiarrhythmic therapy, during MEX and Q monotherapies, and during combination therapy. During monotherapy, the daily doses and serum drug levels were: MEX, 621 mg/day and 3.4 microM/L; Q, 1573 mg/day and 8.3 microM/L, respectively. With combination therapy, the daily doses and serum drug levels were: MEX, 636 mg/day and 3.3 microM/L; Q, 1643 mg/day and 9.5 microM/L, respectively. Drug therapy did not affect group LVEF (drug free = 36 +/- 19%, MEX = 34 +/- 18%, Q = 36 +/- 19%, and combination MEX-Q = 35 +/- 19%), RVEF (drug free = 34 +/- 11%, MEX = 35 +/- 11%, Q = 36 +/- 13%, and combination MEX-Q = 36 +/- 12%), or WMS. Ventricular function reserve was assessed in five patients. Drug therapy did not affect group exercise LVEF (drug free = 44 +/- 14%, MEX = 42 +/- 12%, Q = 43 +/- 13%, and MEX-Q = 45 +/- 12%), RVEF (drug free = 38 +/- 10%, MEX = 40 +/- 11%, Q = 39 +/- 12%, and MEX-Q = 40 +/- 12%), WMS, or exercise duration. Combination MEX-Q therapy did not have a significant effect on exercise performance or ventricular function in seven additional patients in whom no exercise studies were done during monotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed1988

Multicore myopathy: not always a benign entity.

Four patients with Multicore Myopathy, a rare morphologically distinct myopathy, are described. Although previously considered to be a non-progressive or only slowly progressive myopathy, progression to significant disability was seen in three of our cases. The association of cardiac disease with Multicore Myopathy has not been previously emphasised. All four patients in this study had a cardiomyopathy, and heart disease was the cause of death in two of the patients. Multicore Myopathy is not always a benign entity. Cardiac involvement, when present, adversely affects prognosis.

Adolescent↗
PubMed1988

Procainamide in vivo modulates suppressor T lymphocyte activity.

Autoantibodies to histone and denatured DNA have been found in 80% of patients treated with procainamide. Of these 10 to 20% will eventually develop a Systemic Lupus Erythematosus-like syndrome. Although the mechanism by which procainamide exerts its effect is unknown, in vitro studies suggest that procainamide may inhibit suppressor T cell activity. We have studied the immune function of 18 patients receiving a two hour infusion of procainamide during transvenous catheter electrophysiologic studies. There was no difference between pre and post infusion samples with respect to T and B cell mitogenesis or pokeweed mitogen-induced immunoglobulin secretion. However, in seventeen of eighteen patients, there was a marked decrease in Concanavalin A-inducible suppressor cell activity. This decrease appeared to be related to the amount of procainamide infused as high dose samples showed less suppressor activity than low dose samples. Thus the data show that procainamide, when given in vivo, leads to a rapid and dose dependent decrease in suppressor cell activity.

Adult↗
PubMed1987

A randomized clinical trial of the noninvasive and invasive approaches to drug therapy of ventricular tachycardia.

There is controversy over whether therapy to prevent ventricular tachyarrhythmias should be selected noninvasively (by trying drugs and monitoring the patient electrocardiographically) or invasively (by selecting a drug that prevents induction of the arrhythmia by programmed stimulation). We randomly assigned 57 patients with symptomatic and demonstrable ventricular tachyarrhythmias to therapy selected either noninvasively or invasively. The tachyarrhythmias involved were sustained ventricular tachycardia (35 patients), nonsustained ventricular tachycardia with hypotension (15 patients), and ventricular fibrillation (7 patients). The noninvasive approach sought reduction of ventricular premature beats by more than 80 percent and of couplets by more than 90 percent, with elimination of three or more successive ventricular beats on ambulatory monitoring and exercise testing. The invasive approach sought to prevent the induction of five or more repetitive beats by programmed stimulation. The noninvasive approach required fewer drug trials (3.2 +/- 1.8 [mean +/- SD] vs. 5.5 +/- 2.8, P less than 0.001) and fewer hospital days (20 +/- 15 vs. 33 +/- 24, P = 0.01) and identified a therapy predicted to be effective for more patients than did the invasive approach (29 of 29 vs. 15 of 28, P less than 0.001). When a predicted effective therapy was not found, amiodarone was prescribed despite persisting inducibility of ventricular tachycardia. Patients randomly assigned to the noninvasive approach had more symptomatic recurrences of tachyarrhythmia than those treated by the invasive approach (two-year actuarial probabilities of 0.50 +/- 0.10 vs. 0.20 +/- 0.08, P = 0.02). Similar differences were observed when amiodarone recipients were excluded. There were only three deaths from recurrent ventricular tachyarrhythmias--two in the group whose treatment was selected noninvasively and one in the group whose treatment was selected invasively (not significant). We conclude that therapy selected by the invasive approach prevents recurrences of ventricular tachyarrhythmias better than that selected by the noninvasive approach.

Anti-Arrhythmia Agents↗
PubMed1987

Procainamide, disopyramide and quinidine: discordant antiarrhythmic effects during crossover comparison in patients with inducible ventricular tachycardia.

A crossover comparison of intravenous procainamide, disopyramide and quinidine was made in 32 patients. All three drugs had dosage-related effects on electrocardiographic intervals, refractory periods and cycle length of ventricular tachycardia. Significant linear relations between serum drug levels and changes in refractory periods and ventricular tachycardia cycle length were also observed. Ventricular tachycardia was no longer inducible on at least one drug in 11 patients but concordance of this effect on both of the others was 36% and on either of the others it was 45%. Ventricular tachycardia remained inducible on at least one drug in 28 patients and concordance of this effect on both of the others was 75% and on either of the others was 79%. Continued inducibility on quinidine, the drug producing the greatest electrophysiologic effects, was the best individual predictor of continued inducibility on the others. Subdivision of continued inducibility into easier to induce, inducibility unchanged, or harder to induce dramatically decreased concordance of this effect. Thus the antiarrhythmic effects of these drugs are discordant in individual patients despite electrophysiologic similarities. Nevertheless, continued inducibility after high dosages of any one of these drugs is clinically useful for screening for continued inducibility on the others and this is dose-related rather than drug specific.

Adult↗
PubMed1987

Mexiletine-quinidine combination: electrophysiologic correlates of a favorable antiarrhythmic interaction in humans.

Combination therapy with mexiletine and quinidine has been shown to be more effective than either agent alone. The ability of mexiletine monotherapy, quinidine monotherapy and mexiletine-quinidine combination therapy to suppress inducible sustained ventricular tachycardia was related to drug-induced changes in ventricular refractoriness, conduction times and monophasic action potential duration recorded from both ventricles. Ventricular tachycardia could no longer be induced in 7 (35%) of the 20 patients studied with combination therapy. This was a significantly higher proportion of patients than that of the groups responding to either monotherapy (quinidine, 10%; mexiletine, 5%). Ventricular effective and functional refractory periods were measured when applying single (S2), double (S3) and triple (S4) extrastimuli. Quinidine monotherapy increased functional and effective refractory periods of both single and multiple extrastimuli. However, when comparing measurements made during mexiletine treatment with those at baseline, mexiletine monotherapy increased only the refractory periods of S4. The effective refractory period of S4 during mexiletine monotherapy (200 +/- 20 ms) was significantly longer than at baseline (160 +/- 21 ms). Similarly, when comparing measurements made during combination therapy with those during quinidine monotherapy, combination therapy significantly increased the refractory periods only of multiple extrastimuli. The effective refractory period of S4 during combination therapy (253 +/- 26 ms) was significantly longer than that of quinidine monotherapy (223 +/- 27 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗