title: Beneficial cardiac effects of cicletanine in conscious rabbits with metabolic syndrome.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Debrecen Medical, Health, and Science Center, Debrecen, Hungary. dr.drimba@gmail.com
authors.forename: László
authors.initials: L
authors.lastname: Drimba
authors.forename: Csaba
authors.initials: C
authors.lastname: Hegedüs
authors.forename: Di
authors.initials: D
authors.lastname: Yin
authors.forename: Réka
authors.initials: R
authors.lastname: Sári
authors.forename: József
authors.initials: J
authors.lastname: Németh
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szilvássy
authors.forename: Barna
authors.initials: B
authors.lastname: Peitl
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D002791:Cholesterol, Dietary; D003243:Consciousness; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D013015:Sotalol / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D002791:Cholesterol, Dietary; D008055:Lipids; D011725:Pyridines; D009569:Nitric Oxide; D013015:Sotalol; C038068:cicletanine; D000242:Cyclic AMP; D006152:Cyclic GMP