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Biomedical subjects

D S Echt

Publications and source records attributed to D S Echt.

At least 37 records · Page 2Linked to original sources
PubMed1989

pH-dependent effects of lidocaine on defibrillation energy requirements in dogs.

Lidocaine increases the energy required for ventricular defibrillation in dogs. Because sodium channel-blocking agents that are weak bases have pH-dependent electrophysiologic effects, we investigated the pH dependence of lidocaine (pKa, 7.9) on internal defibrillation energy requirements in 28 dogs with atrial spring and left ventricular patch electrodes. Results of defibrillation testing were used to derive 50% and 90% successful energy requirements (ED50 and ED90) using logistic regression and were compared with analysis of variance. Acidosis produced by hydrochloric acid infusion decreased the arterial pH from 7.40 +/- 0.05 (SD) to 7.18 +/- 0.03 (n = 8, p less than 0.01), but no significant change in ED90 was observed (14 +/- 4 to 16 +/- 6 J). Lidocaine infusion to therapeutic levels (4.2 +/- .07 micrograms/ml) at normal pH (7.42 +/- 0.02) increased ED90 from 13 +/- 3 to 17 +/- 3 J (n = 6, p less than 0.05), and subsequent acidosis (pH 7.19 +/- 0.02, p less than 0.01) exacerbated this effect of lidocaine on ED90 (22 +/- 5 J, p less than 0.05). Alkalosis produced by respirator hyperventilation increased the arterial pH from 7.41 +/- 0.03 to 7.60 +/- 0.03 (n = 8, p less than 0.01), with a fall in ED90 from 13 +/- 4 to 8 +/- 3 J (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1989

Antiarrhythmic efficacy, clinical electrophysiology, and pharmacokinetics of 3-methoxy-O-desmethyl encainide (MODE) in patients with inducible ventricular tachycardia or fibrillation.

In most patients, the clinical effects of therapy with encainide are mediated by the generation of the active metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide (MODE). Data from in vitro and animal studies have indicated that MODE has electrophysiologic and pharmacokinetic features that make its further evaluation desirable; in earlier studies, we found that MODE suppressed chronic high-frequency nonsustained ventricular arrhythmias at plasma concentrations of 50-160 ng/ml. We now report the clinical electrophysiology, antiarrhythmic activity, and pharmacokinetics of MODE in 17 patients with inducible ventricular tachyarrhythmias (VTs) in whom programmed electrical stimulation was performed before drug administration and after one or two sequences of loading and maintenance infusions of MODE. Because the relation between plasma concentration and effect had been incompletely defined, a dose-titration approach was adopted: available pharmacokinetic data were used to construct loading and maintenance infusion regimens that were predicted to attain low plasma concentrations in initial patients while higher infusion rates were evaluated in subsequent patients. MODE prevented VT induction in three of 17 patients and VT cycle length was increased by greater than or equal to 100 msec in a further seven of 17; most responses to MODE occurred at plasma concentrations greater than 556 ng/ml (greater than 1 SD above mean plasma MODE during encainide therapy). Response to MODE did not predict subsequent response to oral therapy with encainide. MODE increased intracardiac conduction times, QT intervals during atrial and ventricular pacing, and right ventricular effective refractory periods (RVERP); changes in RVERP were most prominent at rapid pacing rates, while changes in intracardiac conduction were rate-independent at cycle lengths between 400 and 600 msec. Plasma MODE concentrations measured during electrophysiology study correlated well with those predicted by the pharmacokinetic simulations (r = 0.91, p less than 0.001). Serial plasma sampling after programmed electrical stimulation indicated a minimum MODE elimination half-life of 8.2 +/- 5.4 hours. Side effects were confined to three instances of asymptomatic conduction system depression in subjects with latent conduction system disturbances. We conclude that MODE slows intracardiac conduction, delays repolarization, and can suppress or substantially modify inducible VT. Moreover, it was only with the adoption of the dose-titration strategy that we were able to safely demonstrate that plasma MODE concentrations higher than those routinely observed during encainide therapy were required to substantially alter cardiac electrophysiology.

Adult↗
PubMed1988

Electrophysiologic effects of intravenous and oral sotalol for sustained ventricular tachycardia secondary to coronary artery disease.

The electrophysiologic effects of intravenous sotalol (1.5 mg/kg load followed by 0.008 mg/kg maintenance, mean dose 150 +/- 23 mg) and oral sotalol (mean dose 583 +/- 204 mg daily) were prospectively evaluated in 16 patients undergoing electrophysiologic evaluation for sustained ventricular tachycardia (VT) secondary to coronary artery disease. Electrocardiographic intervals, indexes of sinus and atrioventricular node function and indexes of atrial and ventricular function were assessed. Inducibility or noninducibility of sustained VT and characteristics of the induced arrhythmia were also evaluated. Intravenous and oral sotalol exerted similar beta-blocking effects, which included significant prolongation of sinus cycle length (baseline 820 +/- 165 ms, intravenous sotalol 1,077 +/- 206 ms, oral sotalol 1,141 +/- 306 ms), AH interval (baseline 126 +/- 43, intravenous sotalol 169 +/- 42, oral sotalol 197 +/- 55 ms) and Wenckebach cycle length (baseline 375 +/- 70, intravenous sotalol 460 +/- 84, oral sotalol 449 +/- 68 ms). Both intravenous and oral sotalol also prolonged repolarization and refractoriness including significant increases in QT interval (baseline 338 +/- 47, intravenous sotalol 417 +/- 35, oral sotalol 450 +/- 70 ms), atrial effective refractory period (baseline 240 +/- 38, intravenous sotalol 330 +/- 71, oral sotalol 299 +/- 26 ms) and right ventricular effective refractory period (baseline 241 +/- 16, intravenous sotalol 289 +/- 35, oral sotalol 291 +/- 22 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Tocainide plus quinidine for treatment of ventricular arrhythmias.

Tocainide and quinidine were administered both as single agents and in combination to 14 patients with chronic ventricular arrhythmias. Therapy with tocainide was limited by the occurrence of dose-related adverse reactions in 8 patients, but could be titrated to a dose that was well-tolerated in 13 of 14 and effective in 2 of 13. The addition of quinidine gluconate to the tolerated dose of tocainide increased the number of patients with arrhythmia suppression from 2 to 6. After tocainide washout, quinidine alone suppressed arrhythmias in only 3 patients. Analysis of electrocardiogram intervals showed that the drugs had additive effects on the coupling interval of the sinus beat to the predominant ectopic beat, but exerted antagonistic effects on the corrected QT interval. These findings suggest that the combination may be clinically useful, exerting pharmacologic effects unlike either agent alone.

Aged↗
PubMed1988

Influence of ventricular fibrillation duration on defibrillation energy in dogs using bidirectional pulse discharges.

The automatic implantable defibrillator device typically discharges 5-30 seconds after detection of ventricular fibrillation. To investigate the importance of the duration of ventricular fibrillation on defibrillation, the effects of ventricular fibrillation durations of 5, 15, and 30 seconds on the energy requirements for successful internal defibrillation were compared in 15 closed chest dogs with internal electrodes. The electrode configuration utilized a transvenous right heart catheter with two electrodes and a precordial subcutaneous patch electrode, with a single bidirectional pulse discharged between the distal catheter electrode and the proximal catheter and patch electrodes. Curves of energy vs. percentage of successful defibrillation were constructed and logistic regression was used to derive 90% and 50% successful energy doses (ED90 and ED50). The mean ventricular fibrillation activation interval just prior to defibrillation was determined from discrete RV endocardial electrograms. Four dogs died during testing, all because of inability to defibrillate after 30 s of ventricular fibrillation. In the remaining 11 dogs, the ED90 increased from (mean +/- SD) 27 +/- 13J at 5 s to 41 +/- 14J at 30 s (p less than .01). The mean ventricular fibrillation activation interval decreased from 107 +/- 21 ms at 5 s to 95 +/- 18 ms at 30 s (p less than .01). In conclusion, the energy required for internal defibrillation in dogs using this electrode configuration increases with longer durations of ventricular fibrillation, and is associated with more rapid ventricular fibrillation activation intervals.

Animals↗
PubMed1988

Antiarrhythmic activity, electrocardiographic effects and pharmacokinetics of the encainide metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide in man.

Although encainide is an effective antiarrhythmic agent, plasma concentrations and pharmacologic effects are not well correlated. One explanation is the generation of active metabolites: while in most patients (extensive metabolizers; EMs) concentrations of the metabolites O-desmethyl encainide (ODE) and 3-methoxy-O-desmethyl encainide (3MODE) are higher than those of encainide, a small subset (poor metabolizers; PMs) lack the ability to extensively biotransform encainide. Considerable data from studies in vitro and animal studies, as well as indirect evidence in patients, indicate that ODE and 3MODE produce the effects seen during long-term encainide therapy in EMs. We now report the initial direct evaluation of the pharmacologic actions of these metabolites of encainide in man. Nine patients with ventricular arrhythmias, seven of the EM phenotype and two of the PM phenotype, were studied. Chronic high-frequency ventricular arrhythmias were suppressed by encainide therapy in seven of nine; monitoring arrhythmia frequency during withdrawal of encainide allowed definition of plasma concentrations of encainide and metabolites associated with arrhythmia suppression. Intravenous infusions of both ODE and 3MODE suppressed chronic ventricular arrhythmias, while infusions of placebo had no effect. ODE clearance was a function of metabolizer phenotype, with higher clearance (mean 914 ml/min; range 554 to 1,314) in EMs than in PMs (434, 298 ml/min); moreover, 3MODE was detected during ODE infusions in all seven EMs but in neither PM. 3MODE clearance was more uniform (mean 289 ml/min in EMs [range 180-410] vs 300 and 78 ml/min in the two PMs) and ODE was not detected in any subject during 3MODE infusion. Encainide itself was not detected after any infusion of ODE or 3MODE. During withdrawal of encainide therapy, ODE plasma concentration at the time of arrhythmia recurrence was 55 +/- 40 ng/ml (mean +/- SD), while ODE by infusion was effective at a concentration of 37 +/- 15 ng/ml. Similarly, plasma concentration of 3MODE at the time of arrhythmia recurrence after withdrawal of chronic encainide was 116 +/- 35 ng/ml and that during 3MODE infusion was 105 +/- 50 ng/ml. While both compounds prolonged QRS duration, ODE was the more potent, increasing QRS by 9.2 +/- 1.6% per 100 ng/ml vs 1.2 +/- 0.5% per 100 ng/ml for 3MODE. On the other hand, 3MODE prolonged the corrected JT interval by 1.9 +/- 0.6% per 100 ng/ml, while ODE shortened it by 2.7 +/- 1.9% per 100 ng/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Role of extrastimulus prematurity and intraventricular conduction time in inducing ventricular tachycardia or ventricular fibrillation secondary to coronary artery disease.

The influence of extrastimulus prematurity and changes in intraventricular conduction time on ventricular tachycardia (VT) inducibility were evaluated in 78 patients with coronary artery disease undergoing electrophysiologic study. In a retrospective portion, the effect of adding ventricular extrastimuli vs shortening the ventricular drive cycle length on extrastimulus prematurity and VT inducibility was evaluated in 59 consecutive patients with inducible ventricular arrhythmias (group I). In a prospective component, changes in intraventricular conduction of the last ventricular extrastimulus and the relation to initiation of VT were evaluated in 19 consecutive patients undergoing programmed electrical stimulation (group II). Single (V2), double (V3) and triple (V4) ventricular extrastimuli were introduced during ventricular drive pacing (V1) at multiple cycle lengths. Although reduction of drive cycle length facilitated arrhythmia induction in 25% of patients, addition of an extrastimulus was a more potent method in group I patients. However, the mechanism of arrhythmia induction is not dependent on attainment of shorter coupling intervals with either method. In group II patients QRS duration and intraventricular conduction time of the extrastimuli increased as the coupling interval was reduced. Significant changes in QRS duration and intraventricular conduction time of the extrastimuli that initiated VT were not observed.

Cardiac Pacing, Artificial↗
PubMed1987

Surgical treatment of pediatric cardiac arrhythmia.

The combination of improved diagnostic techniques, new and potent antiarrhythmia agents, and progress in antiarrhythmia surgical procedures has resulted in successful management of complex cardiac arrhythmia in children. The kinds of arrhythmia that can be considered for possible surgical intervention share several features. Each produces symptoms and usually is hemodynamically compromising. Each requires extensive preoperative and intraoperative electrophysiologic evaluation to establish the mechanism, response to drugs, and suitability for surgery. Although reports of surgical arrhythmia treatment have been limited in children, with increasing success the indications for such treatment may become less stringent. Our recommendations are shown in the Table. In general, patients intolerant of or unresponsive to medical treatment for symptomatic arrhythmia (tachycardia or bradycardia), should be considered candidates for surgical antiarrhythmia procedures. These patients should be referred for testing to cardiac centers staffed by pediatric cardiac electrophysiologists and surgeons experienced in arrhythmia diagnosis and ablation. Careful evaluation can identify those patients in whom surgical approaches are most appropriate. At present, surgical operations for selected, serious pediatric cardiac arrhythmias offer definitive and possibly curative treatment, and may be preferable to inadequate, poorly tolerated, or long-term medical therapy.

Adolescent↗
PubMed1986

Effects of congestive heart failure on the pharmacokinetics and pharmacodynamics of antiarrhythmic agents.

Changes in the pharmacokinetics of antiarrhythmic agents should be expected in patients with congestive heart failure (CHF). The direction of the changes, however, is not always predictable. The volume of distribution is often decreased by as much as 40%, and loading doses should, therefore, be appropriately reduced. Drug clearance may also be diminished due to decreased blood flow to the liver and kidneys, as well as decreased hepatic drug-metabolizing activity. Infusion rates should similarly be lowered to avoid toxicity. However, decreases in both volume of distribution and clearance may result in little, if any, change in elimination half-life, despite higher plasma concentrations. On the other hand, the elimination half-life of antiarrhythmic agents that have a large volume of distribution and are highly cleared by the liver may be twice as long in patients with CHF compared with normal subjects. Thus, the total daily dose of drug should also be lower in these patients. In addition, the time necessary to reach steady state is longer, so that premature dose escalation may lead to excessive drug accumulation. In terms of their pharmacodynamic effects, all antiarrhythmic agents have the potential to manifest a degree of negative inotropy, which must be anticipated as a possible side effect in patients with CHF. Some of the newer agents, such as tocainide and encainide, appear to cause only minimal myocardial depression. Other potential complications of all antiarrhythmic therapy include proarrhythmia and possible drug interactions with digitalis and diuretics.

Amiodarone↗
PubMed1986

Ethmozine: electrophysiology, hemodynamics, and antiarrhythmic efficacy in patients with life-threatening ventricular arrhythmias.

Thirteen patients with drug-resistant, life-threatening ventricular arrhythmias and inducible sustained ventricular tachycardia (VT) at electrophysiologic study received moricizine HC1 (ethmozine), 10 mg/kg/day orally. Eight patients underwent electrophysiologic study before and after drug administration; the arrhythmia became noninducible in one. In five other patients, spontaneous sustained VT occurred after 1 to 5 days of drug therapy, and one patient had a worsening of arrhythmias on ethmozine. Ethmozine prolonged infranodal conduction time (HV interval) (51.4 +/- 13.8 msec to 69.3 +/- 17.7 msec [mean +/- SD]), PR interval (201 +/- 28.1 msec to 244 +/- 62.2 msec), and QRS interval (123 +/- 27 msec to 147 +/- 32 msec). Ventricular refractory periods were not consistently affected, and only the one patient who became noninducible had an increase in effective ventricular refractory period (280 to 310 msec). The drug had no significant effect on sinus cycle length or sinus node recovery time, atrial conduction or refractoriness, or atrioventricular nodal refractoriness. Ethmozine had no effect on radionuclide ejection fraction (25.5 +/- 12.7% to 28.2 +/- 13.8%) or cardiac index (2.4 +/- 0.7 to 3.0 +/- 0.6 ml/min/m2) and caused no significant changes in mean aortic, right atrial, pulmonary arterial, or pulmonary capillary wedge pressures. Although the drug is well tolerated and produces no untoward hemodynamic effects, ethmozine is relatively ineffective in patients with sustained VT refractory to conventional antiarrhythmic agents.

Adult↗
PubMed1986

Effect of variation in PQ interval on patterns of atrioventricular valve motion and flow in patients with normal ventricular function.

M-mode echocardiography and Doppler ultrasonography were used to study patterns of atrioventricular (AV) valve motion and flow in five patients with complete heart block, normal ventricular function and an implanted dual chamber pacemaker with programmable PQ intervals. Changes in AV valve motion and flow patterns resulting from steady state changes in PQ interval over the range studied (75 to 250 ms) were similar in all patients. Events reflecting AV valve opening and rapid ventricular filling bore a constant temporal relation to the Q wave and were unaffected by changes in PQ interval. Events reflecting atrial contraction occurred progressively earlier in diastole with lengthening of the PQ interval, until superimposition of atrial contraction on rapid ventricular filling at a PQ interval of 250 ms. The duration of mid-diastolic slow ventricular filling and overall diastole, defined with respect to an open valve, decreased with lengthening of the PQ interval. The onset of AV valve closure (A point) bore a constant temporal relation to the P wave, indicating that atrial systole initiated valve closure. However, completion of AV valve closure occurred progressively earlier with respect to the P wave as the PQ interval was decreased. This suggests an increasing contribution of ventricular systole to completion of AV valve closure with decreasing PQ interval. End-diastolic and end-systolic ventricular and atrial dimensions were independent of the PQ interval.

Adolescent↗
PubMed1986

Indications for different modes of surgical therapy in medically refractory ventricular arrhythmias.

Fifty-one adult patients were referred for surgical treatment during the time period from July 1980 to November 1985. The average age was 59 +/- 6 years (19-70 years). All patients had symptomatic ventricular tachycardia that was refractory to standard or experimental drug therapy. On the basis of patient condition, site of arrhythmia, ventricular function, and extent of coronary disease, 21 patients were classed as good risk (GR) while 30 patients were thought to represent a poor surgical risk (PR). Thirty-two patients (15 GR, 17 PR) underwent electrophysiologic guided endocardial resection of arrhythmic foci. The hospital mortality was 12% (4/32), and two additional patients died late. All deaths were in poor risk patients. Recurrent arrhythmia was the primary cause of death in only one patient. Nineteen patients have required automatic internal cardioverter defibrillation (AICD) or chronic burst pacing (BP) with an implantable radiofrequency stimulator, with no operative mortality. AICD implantation was chosen for 13 drug refractory patients who were either poor surgical risk and/or had a tachycardia rate above 130 beats/minute with multiple scars or a multifocal tachycardia. Six additional patients who had tachycardia less than 130 beats/minute and whose arrhythmia could be safely terminated with BP had radiofrequency stimulator implantation. The one late death in this group was in a medically noncompliant patient. On the basis of this experience, we feel that map-guided endocardial resection should be offered to all good risk patients with a single scar and unifocal tachycardia who are refractory to medical treatment. This operation should be considered in all patients who have frequent, life-threatening attacks of tachycardia of any sort on maximum drug therapy. The remainder can be well managed with an AICD if their tachycardia rate is greater than 130 beats/minute or with BP using a radiofrequency stimulator.

Adult↗
PubMed1985

Treatment with oral lorcainide in patients with sustained ventricular tachycardia and fibrillation.

Fifty patients with drug-refractory (failed 7 +/- 2 other drug trials) sustained ventricular tachycardia or fibrillation were treated with oral lorcainide. Twenty-three patients underwent programmed stimulation both before and after oral lorcainide, and all 23 remained inducible, although ventricular tachycardia cycle length was prolonged and mean arterial pressure was higher. Lorcainide was discontinued in 23 patients prior to hospital discharge because of death in four patients, side effects in five patients, spontaneous clinical arrhythmia recurrence in six patients, and ventricular tachyarrhythmias induced at electrophysiologic study in eight patients. Twenty-seven patients were discharged on an average dose of 169 +/- 56 mg twice a day, including 15 in whom ventricular tachycardia remained inducible. During long-term follow-up the drug was discontinued in 15 patients; three because of side effects, three because of clinical nonfatal arrhythmia recurrence, two who selected other alternative therapy, and seven patients who died suddenly due to ventricular tachyarrhythmias. Twelve patients remain on long-term lorcainide. The actuarial 1-year chance of being arrhythmia free was 38.9%, and 1-year cardiovascular and arrhythmia survival rates were 56.8% and 60.4%, respectively. Based on our data we conclude that: In this extremely drug-resistant patient population the clinical efficacy of lorcainide is low; lorcainide should not be used empirically in such highly drug-resistant patients; persistent ventricular tachyarrhythmia inducibility at electrophysiologic study implies a poor prognosis in patients treated with oral lorcainide; the incidence of becoming noninducible during oral lorcainide therapy in highly drug-resistant patients appears low; and for patients in whom the drug seems partially beneficial it could be used in conjunction with a backup automatic implantable cardioverter/defibrillator.

Administration, Oral↗
PubMed1985

Clinical experience, complications, and survival in 70 patients with the automatic implantable cardioverter/defibrillator.

Seventy patients received the automatic implantable defibrillator, five original devices and 72 modified second-generation devices using only bipolar rate sensing and delivering an R wave synchronous cardioverting/defibrillating shock, for either ventricular tachycardia or fibrillation. The primary clinical arrhythmia was sustained ventricular tachycardia in 32 patients, ventricular fibrillation in 20 patients, and both ventricular tachycardia and fibrillation in 18 patients. Before implantation of the device the patients had survived 3.1 +/- 2.3 arrhythmic episodes, including 1.9 +/- 1.7 cardiac arrest, and had received 4.0 +/- 2.1 antiarrhythmic drugs without improvement. Sixty-eight patients ultimately received devices. After a follow-up period of 8.9 +/- 7.7 months (range 1 to 33), 37 patients received a total of 463 discharges. Inability to determine the precise reason for most discharges and the unpleasant nature of the discharges were the major clinical problems encountered. Complications included postoperative death (one patient), lead problems (six patients), inadequate energy requiring explanation (two patients), and pocket infection (one patient. Life-table analysis revealed 6 and 12 month cardiovascular survival of 95.0% and 89.9% and sudden death survival of 98.2%. In our experience, survival with the automatic implantable cardioverter/defibrillator exceeds that with other forms of therapy.

Arrhythmias, Cardiac↗
PubMed1984

Facilitation of ventricular tachyarrhythmia induction by isoproterenol.

Ventricular tachyarrhythmia induction was facilitated during infusion of isoproterenol in 21 of 60 patients with ventricular tachycardia (VT) or ventricular fibrillation (VF) in whom programmed electrical stimulation alone failed to reproducibly induce sustained ventricular tachyarrhythmias. Of 44 patients with no ventricular tachyarrhythmias induced before isoproterenol infusion, 11 had a sustained ventricular tachyarrhythmia and 1 patient had unsustained VT induced by isoproterenol alone or by programmed stimulation during the infusion. In 9 of 16 patients in whom nonreproducible or unsustained ventricular tachyarrhythmias were induced before isoproterenol infusion, more reproducible or more sustained ventricular tachyarrhythmias were induced during the infusion. Tachyarrhythmia induction was facilitated by isoproterenol in 20 of 40 patients with sustained VT clinically, but in only 1 of 20 patients with unsustained VT or VF clinically. Among patients with sustained VT clinically, those with exercise-provoked VT and those who had not been tested with stimulation at a second right ventricular site or in the left ventricle were more likely to have induction facilitated by isoproterenol. Drugs effective against induction of isoproterenol-facilitated ventricular tachyarrhythmias were identified in 13 of 25 trials. These drugs were effective during a mean follow-up of 17 months in 7 of 9 long-term trials.

Anti-Arrhythmia Agents↗