Cromakalim and cicletanine against pacing-induced myocardial ischemia in conscious rabbits

Szilvássy, Zoltán; Koltai, M.; Ferdinándy, Péter; Jakab, I; Lonovics, J.; Tarrade, T; Allard, Michel; Braquet, P.

doi:10.1016/0024-3205(94)00870-1

Cited by 7 publications

(7 citation statements)

References 16 publications

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“…Furthermore, the progressive shortening of the effective refractory period characteristic of atrial fibrillation has been argued to be due to activation of the K ATP channels during rapid atrial rates (39). Conversely, K ATP channel opening by pinacidil or cromakalim has been described to be associated with a reduction in effective refractory periods in experimental models (4,35). Taken together, the lengthened effective refractory period and possible dispersion of refractoriness caused by the absence of K ATP channel may be responsible for an increased susceptibility to arrhythmias.…”

Section: Discussionmentioning

confidence: 99%

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Tong

Porter²,

Liu³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Discussionmentioning

confidence: 99%

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Tong

Porter²,

Liu³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Surgery was performed under aseptic conditions as described previously (Szilvassy et al , 1994a,b,c; 1995). Briefly, the rabbits were anaesthetized with an intravenous bolus of 10 mg kg −1 diazepam (Sigma Chemicals Co, St Louis, MO) and 5 mg kg −1 ketamine (EGIS Pharmaceuticals Co, Budapest, Hungary).…”

Section: Methodsmentioning

confidence: 99%

“…One week after surgery, two consecutive 5 min periods of RVP at a rate of 500 beats min −1 were performed with an interpacing interval of 5 min. The resulting intracavital ST‐segment elevation and increase in left ventricular end‐diastolic pressure (LVEDP), indicators of pacing‐induced myocardial ischaemia were measured after both pacing periods as detailed elsewhere (Szilvassy et al , 1994a,b,c). The first RVP served to estimate ST‐segment elevation produced by a single RVP and to perform a preconditioning challenge.…”

Section: Methodsmentioning

confidence: 99%

The effect of continuous versus intermittent treatment with transdermal nitroglycerin on pacing‐induced preconditioning in conscious rabbits

Szilvássy

Ferdinándy

Nagy

et al. 1997

British J Pharmacology

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1 Tolerance to the hypotensive e ect of nitroglycerin (NG) blocks preconditioning induced by rapid ventricular pacing (RVP) in rabbits. In the present work the e ect of continuous versus intermittent treatment with transdermal nitroglycerin on the pacing-induced preconditioning phenomenon was studied in conscious rabbits. 2 RVP (500 beats min 71 over 5 min) increased left ventricular end-diastolic pressure (LVEDP) from baseline 4.1+0.9 to postpacing 13.8+2.9 mmHg (P50.001) with a right intraventricular ST-segment elevation of 1.25+0.13 mV, two indicators of myocardial ischaemia. These changes were signi®cantly attenuated when the RVP period was preceded by a preconditioning pacing of the same rate and duration with an interpacing interval of 5 min. 3 Protection by preconditioning was abolished when the animals had been made tolerant to the vasodilator e ect of 30 mg kg 71 NG by the application of transdermal NG (approx. 0.07 mg kg 71 h 71 ) over 7 days. Furthermore, transdermal NG per se attenuated both RVP-induced ST-segment elevation and LVEDP-increase over the 7 day period. 4 With intermittent transdermal NG treatment (12 h`patch on' vs`patch o '), neither development of vascular tolerance nor attenuation of the NG-or preconditioning-induced anti-ischaemic e ects were observed. However, the severity of pacing-induced myocardial ischaemia was signi®cantly increased during the`patch o ' periods. 5 In a second set of experiments, postpacing changes in cardiac cyclic GMP and cyclic AMP levels were determined by means of radioimmunoassay in chronically instrumented anaesthetized open-chest rabbits with the same NG-treatment protocols. Preconditioning reduced postpacing increase in cyclic AMP with an increase in cyclic GMP concentrations in hearts of the untreated animals and in those given patches intermittently during both`patch on' and`patch o ' periods. However, the preconditioning e ect on either cyclic nucleotide was blocked in the tolerant animals. 6 Transdermal NG increased resting levels of both cardiac cyclic nucleotides in the non-tolerant but not in the tolerant state. The postpacing increase in cyclic AMP content was inhibited by transdermal NG, independent of vascular tolerance development, whereas, an increase in cyclic GMP content was exclusively seen in the non-tolerant animals. 7 We conclude that the anti-ischaemic e ect of NG is independent of the cyclic GMP mechanism in the tolerant state. While intermittent NG therapy prevents development of vascular tolerance and preserves preconditioning, the nitrate-free periods yield an increased susceptibility of the heart to ischaemic challenges.

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“…GLG-V-13 was selected as a reference because this agent had been documented to have low torsadogenic effects (10,ll). Rabbits underwent a sterile surgery for instrumentation and were allowed to recover for at least x v) one week (39). Six animals in each group received EGIS-7229 or the reference compound, GLG-V-13.…”

Section: Induction Of "Torsades De Points" Polymorphic Ventricular Tamentioning

confidence: 99%

EGIS‐7229: A New Potent Antiarrhythmic Candidate with Combined Mode of Action

Nánási

Szénási

1997

Cardiovascular Drug Reviews

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Cromakalim and cicletanine against pacing-induced myocardial ischemia in conscious rabbits

Cited by 7 publications

References 16 publications

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

The effect of continuous versus intermittent treatment with transdermal nitroglycerin on pacing‐induced preconditioning in conscious rabbits

EGIS‐7229: A New Potent Antiarrhythmic Candidate with Combined Mode of Action

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Cromakalim and cicletanine against pacing-induced myocardial ischemia in conscious rabbits

Cited by 7 publications

References 16 publications

Consequences of cardiac myocyte-specific ablation of KATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Consequences of cardiac myocyte-specific ablation of KATPchannels in transgenic mice expressing dominant negative Kir6 subunits

The effect of continuous versus intermittent treatment with transdermal nitroglycerin on pacing‐induced preconditioning in conscious rabbits

EGIS‐7229: A New Potent Antiarrhythmic Candidate with Combined Mode of Action

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Product

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Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits