Beneficial cardiac effects of cicletanine in conscious rabbits with metabolic syndrome

László Drimba, Csaba Hegedüs, Di Yin, Réka Sári, J. Németh, Z. Szilvássy, Barna Peitl

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE:: High-fat diet and consequent metabolic syndrome (MS) can lead to elevated risk for cardiac arrhythmias. This preclinical study was to investigate if cicletanine (CIC) could produce cardioprotective effects in conscious rabbits exhibiting the main symptoms of MS. METHODS:: NZW rabbits that had undergone an 8-week-long cholesterol-enriched diet (1.5%) were instrumented with a pacemaker electrode and randomly assigned into 3 groups according to the oral treatment of either CIC (50 mg•kg) or sotalol (25 mg•kg) and their placebo b.i.d. over 5 days. Study groups were subjected to either "arrhythmia challenge" by programmed electrical stimulation in the "Arrhythmogenesis" study (N = 54) or global myocardial ischemia by rapid pacing in the "Ventricular Overdrive Pacing-induced Myocardial Ischemia" study (N = 18). The antiarrhythmic effect was evaluated by the establishment of the incidence of programmed electrical stimulation-induced arrhythmias. Proarrhythmia indicators (eg, QTc, Tpeak-Tend) were also measured to assess the cardiac safety profile of CIC. To evaluate the background of antiarrhythmic effect, cardiac cyclic nucleotide (cyclic 3′,5′- guanosine monophosphate [cGMP], cyclic 3′,5′-adenosine monophosphate [cAMP]) and nitric oxide content were determined. The antiischemic effect was characterized by change of intracavital ST segment. RESULTS:: Cicletanine treatment significantly decreased the incidence of ventricular arrhythmias, increased cardiac cGMP and nitric oxide content and reduced cardiac cAMP level. Cicletanine did not modify significantly QTc and Tpeak-Tend interval. The ST-segment change in response to rapid pacing was reduced significantly by CIC. (P <0.05). CONCLUSIONS:: Cicletanine exerts beneficial cardiac effects in rabbits with symptoms of MS, which may be of influence with regard to the clinical application of the drug.

Original languageEnglish
Pages (from-to)208-218
Number of pages11
JournalJournal of Cardiovascular Pharmacology
Volume60
Issue number2
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Rabbits
Cardiac Arrhythmias
Adenosine Monophosphate
Electric Stimulation
Myocardial Ischemia
Nitric Oxide
Sotalol
Cyclic Nucleotides
Incidence
High Fat Diet
cicletanine
Electrodes
Cholesterol
Placebos
Diet
Safety
Therapeutics
Pharmaceutical Preparations
3'-guanylic acid

Keywords

  • cardiac arrhythmias
  • cardiac ischemia
  • cardiac nucleotides
  • cicletanine
  • metabolic syndrome
  • nitric oxide
  • programmed electrical stimulation

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Beneficial cardiac effects of cicletanine in conscious rabbits with metabolic syndrome. / Drimba, László; Hegedüs, Csaba; Yin, Di; Sári, Réka; Németh, J.; Szilvássy, Z.; Peitl, Barna.

In: Journal of Cardiovascular Pharmacology, Vol. 60, No. 2, 08.2012, p. 208-218.

Research output: Contribution to journalArticle

Drimba, László ; Hegedüs, Csaba ; Yin, Di ; Sári, Réka ; Németh, J. ; Szilvássy, Z. ; Peitl, Barna. / Beneficial cardiac effects of cicletanine in conscious rabbits with metabolic syndrome. In: Journal of Cardiovascular Pharmacology. 2012 ; Vol. 60, No. 2. pp. 208-218.
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