Efficacy of epicardial controlled-release lidocaine for ventricular tachycardia induced by rapid ventricular pacing in dogs

A. Sintov, W. A. Scott, R. Siden, R. J. Levy

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The effects of epicardial lidocaine on ventricular tachycardia (VT) induced by rapid ventricular pacing (50 Hz) were studied in dogs. Lidocaine-polyurethane (28% wt/wt) matrixes (40-50 mg, 5 x 5 mm) were placed proximal to bipolar left ventricular epicardial electrodes in open-chest anesthetized dogs (n = 9) after VT was established by rapid ventricular pacing. In the first set of experiments, matrices were removed immediately after VT had converted to sinus rhythm. Control animals underwent VT induction protocol with a nondrug-containing matrix positioned next to the epicardial electrode. In the lidocaine-treated animals, VT conversion was noted in all animals and occurred after 51.7 ± 8.9 s (mean ± SE), with a VT threshold current elevation of 73.5 ± 11.2% above baseline at the time of conversion which progressed to 259 ± 44% of the initial value by 5.4 ± 0.5 min post-matrix placement. Lidocaine 1.4 ± 0.1 mg was delivered to the myocardium at the time of VT conversion (0.11 ± 0.01 mg/kg). In comparison, accelerated VT persisted for 5 min in three of five control animals, and progressed to ventricular fibrillation (VF) in the other two animals. In a separate series of eight dogs, the lidocainepolyurethane matrixes were left in place for 4 h so that we could study the sustained antiarrhythmic action of controlled-release lidocaine on VT induction. The results of these experiments demonstrated a maintenance of the VT threshold elevation at a level of 53.9 ± 10.8% after 4 h, with a net lidocaine dose of 0.52 ± 0.06 mg/k after 4 h of controlled release. Peripheral plasma levels of lidocaine during ≤ 4 h of controlled release ranged from 93.9 to 158.5 ng/ml and were detectable only by fluorescent high-performance liquid chromatography (HPLC). However, regional coronary venous lidocaine levels were in the therapeutic range (1.15-2.63 μg/ml) and remained relatively constant during 4 h of controlled release.

Original languageEnglish (US)
Pages (from-to)812-817
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume16
Issue number5
StatePublished - 1990

Fingerprint

Ventricular Tachycardia
Lidocaine
Dogs
Electrodes
Polyurethanes
Ventricular Fibrillation
Myocardium
Thorax
High Pressure Liquid Chromatography
Maintenance

Keywords

  • Arrhythmia
  • Controlled release
  • Drug delivery
  • Epicardial administration
  • Lidocaine
  • Ventricular tachycardia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Efficacy of epicardial controlled-release lidocaine for ventricular tachycardia induced by rapid ventricular pacing in dogs. / Sintov, A.; Scott, W. A.; Siden, R.; Levy, R. J.

In: Journal of Cardiovascular Pharmacology, Vol. 16, No. 5, 1990, p. 812-817.

Research output: Contribution to journalArticle

@article{c1cb04b9f94e4b54862c202710fcefa0,
title = "Efficacy of epicardial controlled-release lidocaine for ventricular tachycardia induced by rapid ventricular pacing in dogs",
abstract = "The effects of epicardial lidocaine on ventricular tachycardia (VT) induced by rapid ventricular pacing (50 Hz) were studied in dogs. Lidocaine-polyurethane (28{\%} wt/wt) matrixes (40-50 mg, 5 x 5 mm) were placed proximal to bipolar left ventricular epicardial electrodes in open-chest anesthetized dogs (n = 9) after VT was established by rapid ventricular pacing. In the first set of experiments, matrices were removed immediately after VT had converted to sinus rhythm. Control animals underwent VT induction protocol with a nondrug-containing matrix positioned next to the epicardial electrode. In the lidocaine-treated animals, VT conversion was noted in all animals and occurred after 51.7 ± 8.9 s (mean ± SE), with a VT threshold current elevation of 73.5 ± 11.2{\%} above baseline at the time of conversion which progressed to 259 ± 44{\%} of the initial value by 5.4 ± 0.5 min post-matrix placement. Lidocaine 1.4 ± 0.1 mg was delivered to the myocardium at the time of VT conversion (0.11 ± 0.01 mg/kg). In comparison, accelerated VT persisted for 5 min in three of five control animals, and progressed to ventricular fibrillation (VF) in the other two animals. In a separate series of eight dogs, the lidocainepolyurethane matrixes were left in place for 4 h so that we could study the sustained antiarrhythmic action of controlled-release lidocaine on VT induction. The results of these experiments demonstrated a maintenance of the VT threshold elevation at a level of 53.9 ± 10.8{\%} after 4 h, with a net lidocaine dose of 0.52 ± 0.06 mg/k after 4 h of controlled release. Peripheral plasma levels of lidocaine during ≤ 4 h of controlled release ranged from 93.9 to 158.5 ng/ml and were detectable only by fluorescent high-performance liquid chromatography (HPLC). However, regional coronary venous lidocaine levels were in the therapeutic range (1.15-2.63 μg/ml) and remained relatively constant during 4 h of controlled release.",
keywords = "Arrhythmia, Controlled release, Drug delivery, Epicardial administration, Lidocaine, Ventricular tachycardia",
author = "A. Sintov and Scott, {W. A.} and R. Siden and Levy, {R. J.}",
year = "1990",
language = "English (US)",
volume = "16",
pages = "812--817",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Efficacy of epicardial controlled-release lidocaine for ventricular tachycardia induced by rapid ventricular pacing in dogs

AU - Sintov, A.

AU - Scott, W. A.

AU - Siden, R.

AU - Levy, R. J.

PY - 1990

Y1 - 1990

N2 - The effects of epicardial lidocaine on ventricular tachycardia (VT) induced by rapid ventricular pacing (50 Hz) were studied in dogs. Lidocaine-polyurethane (28% wt/wt) matrixes (40-50 mg, 5 x 5 mm) were placed proximal to bipolar left ventricular epicardial electrodes in open-chest anesthetized dogs (n = 9) after VT was established by rapid ventricular pacing. In the first set of experiments, matrices were removed immediately after VT had converted to sinus rhythm. Control animals underwent VT induction protocol with a nondrug-containing matrix positioned next to the epicardial electrode. In the lidocaine-treated animals, VT conversion was noted in all animals and occurred after 51.7 ± 8.9 s (mean ± SE), with a VT threshold current elevation of 73.5 ± 11.2% above baseline at the time of conversion which progressed to 259 ± 44% of the initial value by 5.4 ± 0.5 min post-matrix placement. Lidocaine 1.4 ± 0.1 mg was delivered to the myocardium at the time of VT conversion (0.11 ± 0.01 mg/kg). In comparison, accelerated VT persisted for 5 min in three of five control animals, and progressed to ventricular fibrillation (VF) in the other two animals. In a separate series of eight dogs, the lidocainepolyurethane matrixes were left in place for 4 h so that we could study the sustained antiarrhythmic action of controlled-release lidocaine on VT induction. The results of these experiments demonstrated a maintenance of the VT threshold elevation at a level of 53.9 ± 10.8% after 4 h, with a net lidocaine dose of 0.52 ± 0.06 mg/k after 4 h of controlled release. Peripheral plasma levels of lidocaine during ≤ 4 h of controlled release ranged from 93.9 to 158.5 ng/ml and were detectable only by fluorescent high-performance liquid chromatography (HPLC). However, regional coronary venous lidocaine levels were in the therapeutic range (1.15-2.63 μg/ml) and remained relatively constant during 4 h of controlled release.

AB - The effects of epicardial lidocaine on ventricular tachycardia (VT) induced by rapid ventricular pacing (50 Hz) were studied in dogs. Lidocaine-polyurethane (28% wt/wt) matrixes (40-50 mg, 5 x 5 mm) were placed proximal to bipolar left ventricular epicardial electrodes in open-chest anesthetized dogs (n = 9) after VT was established by rapid ventricular pacing. In the first set of experiments, matrices were removed immediately after VT had converted to sinus rhythm. Control animals underwent VT induction protocol with a nondrug-containing matrix positioned next to the epicardial electrode. In the lidocaine-treated animals, VT conversion was noted in all animals and occurred after 51.7 ± 8.9 s (mean ± SE), with a VT threshold current elevation of 73.5 ± 11.2% above baseline at the time of conversion which progressed to 259 ± 44% of the initial value by 5.4 ± 0.5 min post-matrix placement. Lidocaine 1.4 ± 0.1 mg was delivered to the myocardium at the time of VT conversion (0.11 ± 0.01 mg/kg). In comparison, accelerated VT persisted for 5 min in three of five control animals, and progressed to ventricular fibrillation (VF) in the other two animals. In a separate series of eight dogs, the lidocainepolyurethane matrixes were left in place for 4 h so that we could study the sustained antiarrhythmic action of controlled-release lidocaine on VT induction. The results of these experiments demonstrated a maintenance of the VT threshold elevation at a level of 53.9 ± 10.8% after 4 h, with a net lidocaine dose of 0.52 ± 0.06 mg/k after 4 h of controlled release. Peripheral plasma levels of lidocaine during ≤ 4 h of controlled release ranged from 93.9 to 158.5 ng/ml and were detectable only by fluorescent high-performance liquid chromatography (HPLC). However, regional coronary venous lidocaine levels were in the therapeutic range (1.15-2.63 μg/ml) and remained relatively constant during 4 h of controlled release.

KW - Arrhythmia

KW - Controlled release

KW - Drug delivery

KW - Epicardial administration

KW - Lidocaine

KW - Ventricular tachycardia

UR - http://www.scopus.com/inward/record.url?scp=0025130790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025130790&partnerID=8YFLogxK

M3 - Article

C2 - 1703605

AN - SCOPUS:0025130790

VL - 16

SP - 812

EP - 817

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 5

ER -