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001-es BibID:BIBFORM038424
Első szerző:Drimba László (farmakológus)
Cím:Beneficial Cardiac Effects of Cicletanine in Conscious Rabbits With Metabolic Syndrome / Drimba László, Hegedüs Csaba, Yin Din, Sári Réka, Németh József, Szilvássy Zoltán, Peitl Barna
Dátum:2012
ISSN:0160-2446
Megjegyzések: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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
cicletanine
cardiac arrhythmias
cardiac ischemia
metabolic syndrome
programmed electrical stimulation
cardiac nucleotides
nitric oxide
Megjelenés:Journal of Cardiovascular Pharmacology. - 60 : 2 (2012), p. 208-218. -
További szerzők:Hegedűs Csaba (1983-) (Molekuláris biológus, Cera-Med Kft. Debrecen) Yin, Din Sári Réka (farmakológus) Németh József (1954-) (vegyész, analitikus) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Peitl Barna (1972-) (orvos, farmakológus)
Pályázati támogatás:NKFP_07-A2-2008-0260
EGYÉB
GOP-1.1.2-07/1-2008-0004
EGYÉB
GOP-1.1.1-07/1-2008-0032
EGYÉB
GOP-1.2.1-08-2009-0023
EGYÉB
OTKA-75965
OTKA
TÁMOP-4.2.2.- 08/1-2008-0014
TÁMOP
OM-00174/2008
EGYÉB
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