Cicletanine attenuates overdrive pacing-induced global myocardial ischemia in rabbits

possible role of cardiac nucleotides

Z. Szilvássy, I. Jakab, P. Bor, M. Koltai, T. Tarrade, A. Esanu, P. G. Braquet, J. Lonovics

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: This study examined whether cicletanine, an antihypertensive drug with cGMP phosphodiesterase inhibitory effect, could alleviate ventricular overdrive pacing-induced myocardial ischemia in chronically instrumented rabbits. Methods: An electrode-catheter implanted into the right ventricle was used for pacing (500 bpm over 5 min) and for measuring intracavital ST-segment elevation and ventricular effective refractory period (VERP). PQ and QT intervals were measured in the chest-lead ECG, and dP/dt(max) as well as left ventricular end-diastolic pressure (LVEDP) were recorded through a left intraventricular catheter. In separate groups, mean arterial blood pressure (MABP) was monitored from the right carotid artery. Experiments were performed on conscious rabbits after a week of convalescence. In anesthetized, open-chest rabbits, samples were taken from the left ventricle before and after drug treatment and/or overdrive pacing for determination of cGMP and cAMP contents by radioimmunoassay. Results: Intravenous cicletanine, 30 mg/kg body weight, did not change resting MABP, dP/dt(max), and LVEDP, but it did reduce heart rate and prolonged PQ and QT intervals and VERP. Overdrive pacing produced intracavital Si-segment elevation, increased LVEDP, and decreased dP/dt(max) and MABP. Cicletanine administered 15 minutes before pacing significantly attenuated ST-segment elevation, increased LVEDP, and decreased dP/dt(max) and MABP. In anesthetized animals, cicletanine itself slightly increased cardiac cGMP and cAMP contents. Overdrive pacing moderately increased cGMP and profoundly elevated cAMP, and in overpaced rabbits, cicletanine further increased cGMO and markedly attenuated cAMP content increased by overdrive pacing. Conclusions: These results suggest that in correlation with alterations of cardiac cycle nucleotide contents, cicletanine protects the heart against pacing-induced myocardial ischemia.

Original languageEnglish
Pages (from-to)443-452
Number of pages10
JournalCoronary Artery Disease
Volume4
Issue number5
Publication statusPublished - 1993

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Myocardial Ischemia
Arterial Pressure
Nucleotides
Rabbits
Blood Pressure
Heart Ventricles
Thorax
Catheters
Implanted Electrodes
Body Weight Changes
cicletanine
Phosphoric Diester Hydrolases
Carotid Arteries
Antihypertensive Agents
Radioimmunoassay
Electrocardiography
Heart Rate
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cicletanine attenuates overdrive pacing-induced global myocardial ischemia in rabbits : possible role of cardiac nucleotides. / Szilvássy, Z.; Jakab, I.; Bor, P.; Koltai, M.; Tarrade, T.; Esanu, A.; Braquet, P. G.; Lonovics, J.

In: Coronary Artery Disease, Vol. 4, No. 5, 1993, p. 443-452.

Research output: Contribution to journalArticle

Szilvássy, Z. ; Jakab, I. ; Bor, P. ; Koltai, M. ; Tarrade, T. ; Esanu, A. ; Braquet, P. G. ; Lonovics, J. / Cicletanine attenuates overdrive pacing-induced global myocardial ischemia in rabbits : possible role of cardiac nucleotides. In: Coronary Artery Disease. 1993 ; Vol. 4, No. 5. pp. 443-452.
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AU - Szilvássy, Z.

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AU - Braquet, P. G.

AU - Lonovics, J.

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AB - Background: This study examined whether cicletanine, an antihypertensive drug with cGMP phosphodiesterase inhibitory effect, could alleviate ventricular overdrive pacing-induced myocardial ischemia in chronically instrumented rabbits. Methods: An electrode-catheter implanted into the right ventricle was used for pacing (500 bpm over 5 min) and for measuring intracavital ST-segment elevation and ventricular effective refractory period (VERP). PQ and QT intervals were measured in the chest-lead ECG, and dP/dt(max) as well as left ventricular end-diastolic pressure (LVEDP) were recorded through a left intraventricular catheter. In separate groups, mean arterial blood pressure (MABP) was monitored from the right carotid artery. Experiments were performed on conscious rabbits after a week of convalescence. In anesthetized, open-chest rabbits, samples were taken from the left ventricle before and after drug treatment and/or overdrive pacing for determination of cGMP and cAMP contents by radioimmunoassay. Results: Intravenous cicletanine, 30 mg/kg body weight, did not change resting MABP, dP/dt(max), and LVEDP, but it did reduce heart rate and prolonged PQ and QT intervals and VERP. Overdrive pacing produced intracavital Si-segment elevation, increased LVEDP, and decreased dP/dt(max) and MABP. Cicletanine administered 15 minutes before pacing significantly attenuated ST-segment elevation, increased LVEDP, and decreased dP/dt(max) and MABP. In anesthetized animals, cicletanine itself slightly increased cardiac cGMP and cAMP contents. Overdrive pacing moderately increased cGMP and profoundly elevated cAMP, and in overpaced rabbits, cicletanine further increased cGMO and markedly attenuated cAMP content increased by overdrive pacing. Conclusions: These results suggest that in correlation with alterations of cardiac cycle nucleotide contents, cicletanine protects the heart against pacing-induced myocardial ischemia.

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