Quantitative Comparison of Bretylium With Other Antifibrillatory Drugs

Bacaner, Marvin B.

doi:10.1097/00132586-196902000-00011

Cited by 14 publications

(47 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The antiarrhythmic agents used in their study have been shown to increase the VFT in experimental animals. [47][48][49] The protection afforded by these drugs against sudden death may be due to a decrease in the asynchrony of recovery of the ventricles.…”

Section: Clinical Relevancementioning

confidence: 99%

The effects of coronary artery disease on the ventricular fibrillation threshold in man.

Horowitz¹,

Spear²,

Josephson³

et al. 1979

Circulation

View full text Add to dashboard Cite

The ventricular fibrillation threshold (VFT) was measured in 28 patients at the time of cardiac surgery. The VFT was measured with a 100 Hz train of 24 rectangular pulses positioned across the ST segment and T wave. Current was applied to the epicardial surface of either ventricle with a bipolar electrode probe. In six patients, the normal right VFT was 24.3 +/- 5.2 mA, and in 10 patients the normal left VFT was 33.6 +/- mA (p less than 0.05). In 12 patients with greater than or equal to 75% obstruction of the left anterior descending coronary artery, the left VFT was 18.6 +/- 6.9 mA. This value was significantly less than the left VFT in patients without coronary artery disease (p less than 0.001). This study shows that the VFT can be measured in man and that coronary artery disease reduces this parameter.

show abstract

Section: Clinical Relevancementioning

confidence: 99%

The effects of coronary artery disease on the ventricular fibrillation threshold in man.

Horowitz¹,

Spear²,

Josephson³

et al. 1979

Circulation

View full text Add to dashboard Cite

show abstract

“…8 ' 9 Conflicting results appear in the literature, with some studies showing procaine amide (PA) to decrease excitability in a variety of species, 10 " 12 whereas one failed to show any significant effect. 13 Although in these studies there are many differences in experimental technique, part of the variability in the results may be attributed to the fact that the "current threshold" is determined by a complex set of passive and active membrane properties.…”

Section: The Effect Of Procaine Amide On Components Of Excitability Imentioning

confidence: 99%

“…This may explain in part some of the conflicting reports of studies on excitability in the whole animal. 10 " 13 The variablity in excitatory current requirement would have remained uninterpretable if the various components of excitability had not been assessed individually. Our investigation has demonstrated that PA alters both passive RC and active membrane properties, with the net threshold current requirement determined by the balance between the two.…”

Section: Implications Regarding Arrhythmogenesis and Antiarrhythmic Mmentioning

confidence: 99%

The effect of procaine amide on components of excitability in long mammalian cardiac Purkinje fibers.

Arnsdorf¹,

Bigger²

1976

Circulation Research

View full text Add to dashboard Cite

SUMMARY The microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording was used to study the effects of procaine amide (PA) on cardiac excitability. We measured the effect of PA in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 jig/ml), on nonnormalized and normalized strength-duration and charge-duration curves, membrane characteristics, and cable properties in long sheep Purkinje fibers in normal Tyrode's solution with [K + ] o = 4.0 DIM. PA exerted a complex action and influenced passive resistance-capacitance (RC) and active generator properties by decreasing membrane conductance, primarily membrane sodium conductance. Whether PA increased or decreased excitability depended on the relative contribution of the drug-induced alterations in passive and active membrane properties. These findings may explain, in part, the conflicting results of studies on cardiac excitability in the whole animal, as well as the clinical observation that PA may exert both artiarrhythmic and arrhythmogenic effects. The primary mechanism by which PA modifies excitability would seem to differ considerably from that of the structurally similar local anesthetic agent lidocaine.PROCAINE AMIDE is effective in the treatment of both supraventricular and ventricular arrhythmias, and its clinical and electrophysiological effects have been reviewed recently. '"'In the past, cardiac excitability has been assessed primarily in the whole animal, and the index investigated has been the "threshold" current sufficient to elicit a response in studies on either strength-duration requirements or multiple response thresholds. 8 ' 9 Conflicting results appear in the literature, with some studies showing procaine amide (PA) to decrease excitability in a variety of species, 10 " 12 whereas one failed to show any significant effect.13 Although in these studies there are many differences in experimental technique, part of the variability in the results may be attributed to the fact that the "current threshold" is determined by a complex set of passive and active membrane properties.The microelectrode method for intracellular current application and transmembrane voltage recording allows definition of the individual components of excitability which include the resting transmembrane voltage, threshold voltage, membrane conductance, and cable properties.1 *" 18Although the studies have been few, strength-duration and charge-duration curves have been obtained for the isolated Purkinje fiber preparation with this technique and the determinants of excitability analyzed. 14 " 18 In our present investigation we studied excitability by applying this microelectrode technique to long cardiac Purkinje fibers to determine the effects of PA at concentrations equivalent to clinically effective antiarrhythmic plasma levels. Methods EXPERIMENTAL ARRANGEMENTWe used Purkinje fiber preparations obtained from female sheep anesthetized with sodium pentobarbital (30 mg/ kg). "Long" ...

show abstract

“…Conversely, Bacaner [1968] and Cervoni et al [1971] have reported that the adrener gic neuron blockade with guanidinium, guanethidine, had no antifibrillatory effect in the anesthetized dog, and, in addition, Ba caner [1968] demonstrated a reversal of bretylium's antifibrillatory action with guanethidine. If the antifibrillatory property of bre tylium was due solely to cardiac sympathetic neuron blockade, then another adrenergic neuron blocking drug such as guanethidine should also be antifibrillatory.…”

Section: Discussionmentioning

confidence: 99%

Antifibrillatory Action of Bretylium: Role of the Sympathetic Nervous System

Kopia¹,

Lucchesi²

1987

Pharmacology

View full text Add to dashboard Cite

This study was performed to assess the role of cardiac sympathetic nerves in the in vivo antifibrillatory action of bretylium using the technique of electrically induced ventricular fibrillation. An initial study determined that 3 mg/kg of nortriptyline, an adrenergic amine uptake inhibitor, was sufficient to prevent the adrenergic neuron blockade produced by 5 mg/kg of bretylium in pentobarbital anesthetized dogs. Electrical ventricular fibrillation threshold (VFT) was then determined in two groups of pentobarbital anesthetized dogs using gated trains of increasing current applied to the epicardial surface of the right ventricle during atrial pacing. After determination of an initial VFT in both groups, one group of dogs (n = 8) received 3 mg/kg nortriptyline, the other group received saline (n = 9). The VFT was redetermined in both groups, after wich all dogs received 5 mg/kg of bretylium, intravenously, and VFT was then measured at 15 and 90 min after bretylium. In saline-treated dogs, bretylium produced a significant increase in VFT from a control value of 6.9 ± 1.6 mA (X ± SEM) to 31.0 ± 0.5 mA at 15 min (p < 0.05) and 45.1 ± 4.8 mA at 90 min (p < 0.05). In nortriptyline-treated dogs, however, nortriptyline itself produced an increase in VFT which was reversed by bretylium, and VFT after bretylium was not significantly elevated until 90 min to a value of 25.2 ± 9.6 mA (control: 5.2 ± 0.9 mA). These data demonstrate that pretreatment with nortriptyline attenuates and delays the onset of the acute antifibrillatory effect of bretylium and suggests a role for the cardiac adrenergic neuron as a potential target for part of the beneficial effects to be derived from antifibrillatory drugs.

show abstract

Quantitative Comparison of Bretylium With Other Antifibrillatory Drugs

Cited by 14 publications

References 0 publications

The effects of coronary artery disease on the ventricular fibrillation threshold in man.

The effects of coronary artery disease on the ventricular fibrillation threshold in man.

The effect of procaine amide on components of excitability in long mammalian cardiac Purkinje fibers.

Antifibrillatory Action of Bretylium: Role of the Sympathetic Nervous System

Contact Info

Product

Resources

About