Experimental evidence for autowaves in the heart.
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Animals↗
Biomedical subjects
K M Kavanagh
Publications and source records attributed to K M Kavanagh.
Strength-duration and probability of success curves for defibrillation with biphasic waveforms.
Certain biphasic waveforms require less energy to defibrillate than do monophasic pulses of equal duration, although the mechanisms of this increased effectiveness remain unclear. This study used strength-duration and percent success curves for defibrillation with monophasic and biphasic truncated exponential waveforms to explore these mechanisms. In part 1, defibrillation thresholds were determined for both high- and low-tilt waveforms. The monophasic pulses tested ranged in duration from 1.0 to 20.0 msec, and the biphasic waveforms had first phases of either 3.5 or 7.0 msec and second phases ranging from 1.0 to 20.0 msec. In part 2, defibrillation percent success curves were constructed for 6.0 msec/6.0 msec biphasic waveforms with a constant phase-one amplitude and with phase-two amplitudes of approximately 21%, 62%, 94%, and 141% of phase one. This study shows that if the first phase of a biphasic waveform is held constant and the second phase is increased in either duration or amplitude, defibrillation efficacy first improves, then declines, and then again improves. For pulse durations of at least 14 msec, the second-phase defibrillation threshold voltage of a high-tilt biphasic waveform is higher than that of a monophasic pulse equal in duration to the biphasic second phase (p less than 0.05), indicating that the previously proposed hypothesis of stimulation by the second phase is not the sole mechanism of biphasic defibrillation. These facts indicate the importance of the degree of tilt for the defibrillation efficacy of biphasic waveforms and suggest at least two mechanisms exist for defibrillation with these waveforms, one that is more effective for smaller second phases and another that becomes more effective as the second phase is increased.
Animals↗
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↗
Comparison of the internal defibrillation thresholds for monophasic and double and single capacitor biphasic waveforms.
Implantable cardiac defibrillators are now an accepted form of therapy for patients with life-threatening ventricular arrhythmias that cannot be controlled by antiarrhythmic drugs. These devices could be made even more acceptable if they were smaller, had increased longevity and the surgical procedure for implantation was less invasive. Reducing the energy requirements for internal defibrillation with use of a nonthoracotomy system would make all of these goals achievable. Monophasic and double and single capacitor biphasic waveforms were compared in 14 anesthetized dogs (25.5 +/- 2.2 kg) with use of a nonthoracotomy lead system that has previously been shown to distribute the delivered voltage throughout the heart more equally. Cathodal catheter electrodes were placed in the right ventricular apex and outflow tract. The anodal electrode was a large cutaneous R2 patch placed over the left side of the chest. The mean energy requirement for defibrillation when a single capacitor biphasic waveform was used was significantly less (6.4 +/- 2.6 J) than that for either the double capacitor biphasic or the monophasic waveform (18.0 +/- 8.0 and 17.4 +/- 8.0 J, respectively) of the same duration. Unexpectedly, the leading edge voltage for the phase I of the single capacitor biphasic waveform was significantly less (266 +/- 51 V) than that for either the double capacitor biphasic or the monophasic waveform (336 +/- 76 and 427 +/- 117 V, respectively). In conclusion, in large dogs, defibrillation is possible at low energy levels with a single capacitor biphasic waveform.
Animals↗
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↗
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↗
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↗
Ventricular arrhythmias.
Sudden cardiac death claims thousands of Canadians annually. Ventricular tachycardia and fibrillation account for up to 85% of these deaths. Identifying the patients at risk remains a major challenge. Those who have recurrent ventricular tachycardia or have been resuscitated from ventricular fibrillation are generally considered to be at highest risk. Although ventricular premature beats in the absence of previous ventricular tachycardia or fibrillation are not helpful in identifying such patients in most cases, they can indicate increased risk for sudden cardiac death in the presence of a structural cardiac abnormality, particularly recent myocardial infarction; however, the need for treatment in such cases is speculative and is being investigated. Treatment is mandatory for survivors of an episode of ventricular fibrillation and those with recurrent sustained ventricular tachycardia or torsade de pointes ventricular tachycardia. The approach to management is either invasive or noninvasive. Selection of an antiarrhythmic agent is facilitated by knowledge of some basic electrophysiologic features of the heart and of the classification of antiarrhythmic drugs. However, drug therapy has to be individualized on the basis of efficacy, left ventricular function and adverse effects or potential adverse effects of the drug. Amiodarone therapy or nonpharmacologic therapy should be considered if a suitable antiarrhythmic agent cannot be found.
Anti-Arrhythmia Agents↗