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Biomedical subjects

L B Mitchell

Publications and source records attributed to L B Mitchell.

At least 91 records · Page 5Linked to original sources
PubMed1987

Electropharmacology of sotalol in patients with Wolff-Parkinson-White syndrome.

The beta-adrenoceptor-blocking and class III effects of sotalol were assessed in 11 patients with inducible orthodromic reciprocating tachycardia. Serum sotalol concentration, maximum exercise heart rate, and electrophysiologic study data were obtained at control, at the beta-adrenoceptor-blocking dosage (407 +/- 149 mg/day, 1.4 +/- 0.5 micrograms/ml), and at the maximum well-tolerated dosage (924 +/- 337 mg/day, 3.2 +/- 1.3 micrograms/ml). Class III effects (increases in anterograde and retrograde accessory connection effective refractory periods, ventricular effective refractory period, and the QT interval during fixed-rate atrial pacing) were evident at the beta-adrenoceptor-blocking dosage of sotalol and became more marked at the maximum well-tolerated dosage. For example, the mean anterograde accessory connection effective refractory period was significantly increased over control (272 +/- 41 msec) by the beta-adrenoceptor blocker (324 +/- 52 msec) and was further significantly increased by the maximum well-tolerated dose (364 +/- 37 msec). Similarly, the minimum preexcited RR interval during atrial fibrillation was increased in all patients at each dosage tested. Antiarrhythmic efficacy, defined by the absence of inducible, sustained, orthodromic reciprocating tachycardia and a minimum preexcited RR interval during atrial fibrillation of 300 msec or greater, was achieved in four patients at the beta-adrenoceptor-blocking dosage and in another four patients at the maximum well-tolerated dosage. These eight patients received long-term sotalol therapy and none has had recurrent, sustained reciprocating tachycardia during 15 +/- 12 months of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Usefulness of noninvasive studies for diagnosis of right ventricular dysplasia.

The value and limitations of echocardiography and cardiac scintigraphy in the diagnosis of right ventricular (RV) dysplasia were assessed. Criteria that defined RV dysfunction were developed first using data from 40 normal subjects. The sensitivity and specificity of these criteria to detect RV dysplasia were then determined in 44 patients suspected of having RV dysplasia. In these patients the presence (14 patients) or absence (30 patients) of RV dysplasia had been established using cardiac catheterization data, which included contrast RV cineangiograms. Mean RV end-diastolic and end-systolic diameters, and RV/left ventricular (LV) ratios of end-diastolic and end-systolic diameters and end-diastolic and end-systolic volumes were greater in patients with RV dysplasia (p less than 0.001). Using cardiac scintigraphy, all patients with RV dysplasia were identified by an RV/LV end-systolic volume greater than 1.8; exercise RV ejection fraction less than 50%; or exercise RV wall motion score more than 1. Using echocardiography, RV contraction abnormalities were seen in 80% of patients with RV dysplasia. The specificities, even in this selected population, were less than 100%. Thus, normal echocardiographic and scintigraphic results can be used instead of RV contrast cineangiography to exclude the diagnosis of RV dysplasia.

Adult↗
PubMed1986

Programmed electrical stimulation studies for ventricular tachycardia induction in humans. I. The role of ventricular functional refractoriness in tachycardia induction.

Closely coupled extrastimuli are frequently necessary to induce ventricular tachycardia at electrophysiologic study. Although induction usually requires propagated extrastimuli, systematic evaluations of minimal coupling intervals have focused on nonpropagated measures (effective refractory periods) rather than on propagated measures (functional refractory periods). The effects of procedural factors on ventricular functional refractory periods were examined in 10 patients. Like the effective refractory period, the functional refractory period shortens with rapid pacing cycle lengths (281 +/- 12 ms at a cycle length of 600 ms; 260 +/- 15 ms at a cycle length of 400 ms) and with multiple extrastimuli (279 +/- 16 ms with one extrastimulus; 214 +/- 16 ms with two extrastimuli). The effects of multiple extrastimuli exceed those of shortening pacing cycle length. Unlike the effective refractory period, the functional refractory period is affected by recording site (increasing as the distance from the pacing site increases) but is not affected by increasing the stimulus intensity above twice diastolic threshold (282 +/- 14 ms at 2 times threshold; 282 +/- 13 ms at 16 times threshold) or by increasing the pulse width above 2 ms (282 +/- 13 ms at a pulse width of 2 ms; 282 +/- 14 ms at a pulse width of 5 ms). The effect of varying stimulus intensity on ventricular tachycardia induction was examined in a second group of 11 patients with documented, spontaneous ventricular tachycardia. No change in ventricular tachycardia inducibility accompanied changes in stimulus intensity from 2 to 10 times threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Programmed electrical stimulation studies for ventricular tachycardia induction in humans. II. Comparison of indwelling electrode catheter and daily catheter replacement.

Suppression of the ability to induce ventricular tachycardia by programmed electrical stimulation during serial drug testing has been used as a therapeutic end point to identify long-term prophylactic antiarrhythmic therapy. However, ventricular tachycardia induction, particularly with an indwelling electrode catheter, has not been systematically assessed over the time period required for serial drug testing. In this study, the results of programmed electrical stimulation were evaluated daily during serial drug-free conditions before testing various antiarrhythmic drugs. Twenty-four patients were randomly allocated to be studied with the electrode catheter left in place or replaced daily. All patients had inducible sustained ventricular tachycardia during the first study. Loss of the ability to induce ventricular tachycardia occurred in 8 of 13 patients whose catheter was left in place whereas this did not occur in patients whose catheter was replaced daily (p less than 0.01). In addition, use of an in situ catheter was accompanied by significant (p less than 0.05) changes in other electrophysiologic measurements, including number of extrastimuli required to induce ventricular tachycardia and length of ventricular functional and effective refractory periods. The serial changes seen with indwelling catheters in the drug-free state may mimic effective antiarrhythmic drug action.

Adult↗
PubMed1986

Antiarrhythmic efficacy of propranolol: comparison of low and high serum concentrations.

Propranolol has been effective in suppressing ventricular arrhythmias in up to 70% of patients in some series; however, a wide range of concentrations was required to produce this degree of efficacy. In one series, 40% of responders required high serum concentrations (greater than 500 ng/ml) in excess of those required for physiologic beta-receptor blockade (25 to 150 ng/ml). To assess the relative contribution of high concentration electrophysiologic effects to antiarrhythmic efficacy the results of programmed electrical stimulation were compared at high and low (beta-blocking) concentrations in 28 patients with inducible sustained ventricular tachycardia. Propranolol was given as a series of loading and maintenance infusions producing first a mean concentration of 130 +/- 72 ng/ml (beta-blocking) and then a mean concentration of 743 +/- 523 ng/ml (high). Beta-blockade was assessed by the percent reduction in exercise-induced tachycardia. Near maximal beta-blockade was achieved by a concentration of 150 ng/ml. At a low concentration, 6 of 28 patients had a response to propranolol (complete in 5 and partial in 1). At a high concentration, one additional patient had a complete response while three had a partial antiarrhythmic response. At high concentrations of propranolol there was a significant shortening of the QTc interval relative to that seen during the low dose infusion. No other significant electrophysiologic changes occurred at high versus low concentration. In summary, an antiarrhythmic response to propranolol occurs most frequently at a beta-blocking concentration. High concentration electrophysiologic effects occur and these appear to contribute to antiarrhythmic efficacy in some patients.

Adult↗
PubMed1985

Intravenous quinidine: relations among concentration, tachyarrhythmia suppression and electrophysiologic actions with inducible sustained ventricular tachycardia.

A computer simulation was used to devise quinidine sulfate infusions to produce pseudo-steady-state concentrations in the low (8 microM/liter) and high (14 microM/liter) therapeutic ranges, avoiding high peak concentrations. Using this infusion, efficacy and electrophysiologic actions of quinidine sulfate were assessed in 21 patients with sustained inducible ventricular tachycardia (VT) when concentrations were 12.6 +/- 11 microM/liter (mean +/- standard deviation) and 18 +/- 9 microM/liter. Although mean concentrations approximated target levels, there was substantial individual variation. A reciprocal linear relation (r = 0.8, p less than 0.01) was noted between resultant serum concentrations and drug-free ejection fraction (EF). Transient hypotension occurred early in 3 patients, 2 of whom had a normal left ventricular (LV) EF. No hemodynamic compromise was seen in patients with LVEFs of less than 30%. Induced VT was suppressed in 5 patients at low concentrations and in an additional 4 at high concentrations (total 9 of 21, 42%). Concentration-dependent changes in the ventricular effective refractory period of the beat induced by S3 paralleled antiarrhythmic efficacy. Independent of response or lack of response to intravenous quinidine, 17 patients received gradually increasing oral quinidine dosages adjusted to reproduce plasma levels that had been effective during intravenous administration, or to maximal well-tolerated dosage (if side effects occurred). VT was still inducible during oral treatment in 4 of 5 patients in whom VT had been suppressed during the intravenous infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

The power spectrum analyser as an indicator of cerebral ischaemia during carotid endarterectomy.

Stroke is a potential major complication of carotid endarterectomy and may be caused by cerebral ischaemia or embolisation from the operative site. Conventional EEG monitoring has been used intraoperatively to identify periods of cerebral ischaemia, but this monitoring technique can be difficult to operate and interpret in the operating room. This study reports the use of a new signal analyser, the power spectrum analyser (PSA-1, Neurologics, Inc., Nashville, Tennessee), and its impact on active patient management. Thirty-six patients undergoing carotid endarterectomies were monitored with the PSA-1 in conjunction with routine EEG. Eight patients (22%) showed evidence of ischaemia 22 times on both PSA-1 and routine EEG. At no time did the routine EEG show evidence of ischaemia when the PSA-1 did not. The PSA-1 has proven to be a reliable neurophysiologic monitor for the identification of periods of cerebral ischaemia. Use of this small, easily operated and interpreted machine could enhance safety in operating rooms lacking sufficient resources to use conventional EEG machines.

Aged↗
PubMed1984

Clinical efficacy and electrophysiology of imipramine for ventricular tachycardia.

Invasive electrophysiologic studies were performed before and during treatment with imipramine in 18 patients with inducible ventricular tachycardia (VT). All received imipramine, 50 mg twice daily for 3 days, and then 100 mg twice daily for 3 days. Imipramine increased the infranodal conduction times (HV) (from 58 +/- 7.8 to 65 +/- 10 ms) and QRS duration (from 133 +/- 21 to 153 +/- 39 ms) and significantly decreased sinus cycle length (from 875 +/- 145 to 711 +/- 116 ms) and maximal corrected sinus nodal recovery time (from 457 +/- 656 to 380 +/- 603 ms). The Wenckebach cycle length tended to decrease and the QT interval to increase, but these changes were not statistically significant. Atrial and ventricular refractory periods, atrioventricular nodal conduction times and induced VT cycle length did not change significantly. Imipramine prevented induction of VT in 2 patients, and VT was more difficult to induce in 1 patient. These 3 patients received chronic imipramine therapy. The 2 patients in whom no VT could be induced while taking imipramine have had no recurrence of arrhythmia at 6 and 12 months of follow-up. The third patient died suddenly 4 months after discharge from the hospital. One patient had worsening of arrhythmias while taking imipramine and 61% had minor adverse effects. The mean combined plasma imipramine and desmethylimipramine concentration at the time of the repeat electrophysiologic study was 227 +/- 114 ng/ml. Imipramine is effective against VT in some patients; however, like other type I antiarrhythmic drugs, the rate of efficacy is low.

Adult↗
PubMed1984

Recordings of basal ventricular preexcitation from electrode catheters in patients with accessory atrioventricular connections.

To determine the effects of ventricular preexcitation via accessory atrioventricular connections (ACs) on the sequence of basal ventricular activation, electrophysiologic study records of 22 patients with AC were reviewed. In each, AC site was confirmed by mapping done at operation. Local ventricular preexcitation (VP), defined as earlier timing of a local ventricular electrogram relative to the surface electrocardiographic QRS onset in preexcited compared with in normal QRS complexes, was assessed at the coronary sinus and at the ventricular septal summit recorded from the His bundle site. Five patients with concealed AC did not have VP. VP patterns with manifest AC were similar during average fusion QRS complexes and maximum ventricular preexcitation. Left free wall and left crux AC produced VP apparent on the ventricular electrogram recorded at the coronary sinus alone. With anteroseptal AC, VP was noted only at the ventricular septal summit. Posteroseptal AC produced VP that was apparent on the ventricular electrogram recorded at the coronary sinus and on the electrogram of the ventricular septal summit. Right free wall AC preexcited neither of these basal ventricular regions. The observation of VP patterns may help in localizing AC and may be particularly useful in patients without retrograde AC function at electrophysiologic study.

Adolescent↗
PubMed1983

Efficacy of verapamil in chronic, recurrent ventricular tachycardia.

Verapamil, 0.25 mg/kg, was given to 24 patients with chronic, recurrent ventricular tachycardia (VT) whose clinical tachyarrhythmias were reproduced at electrophysiologic study. Seven patients (29%) responded acutely to verapamil: VT was not inducible in 5 and spontaneously terminated within 5 seconds of induction in 2 patients in whom it was previously sustained. Four of the 7 responders had no identifiable structural heart disease, and 3 had coronary artery disease. Responders were younger and had better left ventricular function than did nonresponders. Long-term therapy with verapamil, attempted in 5 of the 7 responders, was effective in 3, ineffective in 1, and of uncertain efficacy in 1. Verapamil therapy was discontinued because of worsened congestive heart failure in 2 patients. The short-term efficacy of verapamil in these patients compares favorably with the efficacy of other antiarrhythmic agents against VT induction in patients with long-term, recurrent, drug-refractory VT. The short-term efficacy of verapamil correlated with its long-term efficacy. These observations provide preliminary evidence that verapamil may be useful in the treatment of some patients with recurrent VT. When standard drugs are not effective, verapamil should be given a trial, especially in young patients with good left ventricular function.

Adult↗
PubMed1983

Comparison of the electrophysiologic effects of intravenous and oral lorcainide in patients with recurrent ventricular tachycardia.

The electrophysiologic effects of intravenous lorcainide (2.2 mg/kg) in 10 patients were compared with the electrophysiologic effects of oral lorcainide (mean dose 400 mg/day for 8 days) in 11 patients, all with recurrent ventricular tachycardia that could be induced with programmed stimulation. Intravenous and oral lorcainide resulted in similar prolongation of the QRS, QT, and HV intervals, but only oral lorcainide resulted in prolongation of the AH interval and atrial and ventricular effective refractory periods. After both oral and intravenous lorcainide, ventricular tachycardia could still be induced, but the arrhythmia was slower and better tolerated hemodynamically. The mean plasma lorcainide level during a maintenance intravenous infusion was 1254 +/- 662 ng/ml compared with a lorcainide level of 562 +/- 41 ng/ml and a norlorcainide level of 1212 +/- 653 ng/ml after oral dosing. No norlorcainide was detected in plasma after intravenous lorcainide. These data suggest that the short-term electrophysiologic effects of intravenous lorcainide may be different from those of short-term therapy with the oral drug. These differences should be considered during short-term studies of lorcainide.

Administration, Oral↗
PubMed1982

Comparative clinical electrophysiologic effects of diltiazem, verapamil and nifedipine: a review.

The slow channel blocking agents--diltiazem, verapamil and nifedipine--have generated clinical interest for the treatment of a variety of cardiovascular disorders. These agents, despite a similar basic mechanism of action, produce disparate clinical cardiac electrophysiologic effects in human beings. In usual doses, the acute administration of diltiazem slows heart rate. Verapamil and nifedipine, however, increase heart rate. Although diltiazem and verapamil produce equivalent slowing of atrioventricular (A-V) nodal conduction, verapamil prolongs A-V nodal refractoriness to a greater degree. In contrast, nifedipine facilitates A-V nodal conduction and shortens A-V nodal refractoriness. Knowledge of these differences may aid in the appropriate selection of specific slow channel blocking agents in specific clinical situations.

Atrioventricular Node↗
PubMed1982

Intracardiac electrophysiologic study of intravenous diltiazem and combined diltiazem-digoxin in patients.

Fifteen patients without sinoatrial (SA) or atrioventricular (AV) node dysfunction underwent electrophysiologic study (EPS) before and after intravenous diltiazem: 0.20 mg/kg bolus followed by 0.0007 mg/kg/min infusion (seven patients) or 0.25 mg/kg bolus followed by 0.0012 mg/kg/min infusion (eight patients). In six patients intravenous digoxin (0.018 mg/kg) was given and 45 minutes later EPS was repeated while the diltiazem infusion continued. Diltiazem prolonged sinus cycle length (+7%, p less than 0.01), lengthened AH conduction time (+22% in constant rate atrial paced rhythm, p less than 0.001), prolonged AV node functional and effective refractory periods (+6%, p less than 0.01 and +16%, p less than 0.05, respectively), lengthened AV node Wenckebach cycle length (+13%, p less than 0.001), shortened atrial functional refractory period (-3%, p less than 0.05), and reduced mean arterial pressure (-8%, p less than 0.005 in constant rate atrial paced rhythm). Subsequently, intravenous digoxin further prolonged sinus cycle length (+12%, p less than 0.05), AH conduction time (+17%, p less than 0.05), AV node Wenckebach cycle length (+9%, p less than 0.05), and AV node functional refractory period (+7%, p less than 0.05), shortened atrial effective refractory period (-7%, p less than 0.05) and ventricular effective refractory period (-6%, p less than 0.05), and increased systolic arterial pressure (+6%, p less than 0.05). Diltiazem and digoxin have additive depressant effects on SA and AV node function without significant adverse effects.

Adult↗
PubMedDate not supplied

A randomized clinical trial of the noninvasive and invasive approaches to drug therapy for ventricular tachycardia: long-term follow-up of the Calgary trial.

Individualized antiarrhythmic drug therapy for patients with ventricular tachyarrhythmias may be selected by the noninvasive approach (suppression of spontaneous ventricular premature beats) or the invasive approach (suppression of ventricular tachyarrhythmias induced at an electrophysiologic study). There is controversy over which approach is superior. From a screened population of 124 patients with symptomatic ventricular tachycardia or ventricular fibrillation, 57 patients with both frequent ventricular premature beats and inducible ventricular tachycardia at baseline were randomized to have chronic therapy selected by either the noninvasive or invasive approach. These patients have now been followed up for a minimum event-free period of 6.5 years. By intention-to-treat, therapy selected by the invasive approach prevented subsequent ventricular tachyarrhythmias better than that selected by the noninvasive approach (6-year probabilities of freedom from symptomatic sustained ventricular tachyarrhythmia recurrence; noninvasive approach, 0.45 +/- 0.10; invasive approach, 0.73 +/- 0.09; p=.02). This advantage of the invasive approach was also evident for the outcome of any ventricular tachyarrhythmia recurrence and for efficacy analyses involving only those patients with a drug-efficacy prediction. We hypothesize that the difference between these results and those of the ESVEM trial are caused, in part, by differences in the characteristics of the enrolled patients and differences in criteria used to define a predicted-effective therapy.

Actuarial Analysis↗
PubMedDate not supplied

Is a baseline electrophysiologic study mandatory for the management of patients with spontaneous, sustained, ventricular tachyarrhythmias?

Should the patient being treated for spontaneous, sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) routinely undergo a baseline, diagnostic, catheter electrophysiologic (EP) study? The potential patient advantages of such a policy include identification of the tachyarrhythmia-initiating episodes of presumed VT or VF, prediction of the subsequent risk of VT/VF recurrences, identification of VT mechanisms amenable to cure by catheter ablation, assessment of the response of a patient's VT to attempts at pace termination, evaluation of the patient's candidacy for some of the approaches to VT/VF therapy selection, and enhancement of our understanding of the mechanisms and therapeutics of VT/VF. Disadvantages of such a policy include patient discomfort, patient risks, and cost. Recognizing that the decision to perform a baseline catheter EP study in a patient with VT/VF must be based on an individualized, patient-based, risk-benefit analysis; this review details each of the advantages and disadvantages of doing so to identify patient populations for whom a baseline catheter EP study is or is not usually indicated.

Cardiac Pacing, Artificial↗