Please use this identifier to cite or link to this item: http://hdl.handle.net/11452/26010
Title: CDP-choline prevents cardiac arrhythmias and lethality induced by short-term myocardial ischemia-reperfusion injury in the rat: Involvement of central muscarinic cholinergic mechanisms
Authors: Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.
Uludağ Üniversitesi/Veteriner Fakültesi/Fizyoloji Anabilim Dalı.
0000-0001-9496-1475
0000-0002-5600-8162
Yılmaz, Mustafa Sertaç
Coşkun, Cenk Nuri
Yalçın, Murat
Savcı, Vahide
AAH-1571-2021
AAG-6956-2021
8895544100
23667159700
57192959734
6603687024
Keywords: CDP-choline
Central
Cholinergic
Muscarinic
Myocardial ischemia-reperfusion
Vagal
Vagal-stimulation
Cytidine
Acetylcholine
Activation
Citicoline
Uridine
Brain
Pharmacology & pharmacy
Issue Date: Sep-2008
Publisher: Springer
Citation: Yılmaz, M. S. vd. (2008). ''CDP-choline prevents cardiac arrhythmias and lethality induced by short-term myocardial ischemia-reperfusion injury in the rat: Involvement of central muscarinic cholinergic mechanisms". Naunyn-Schmiedeberg's Archives of Pharmacology, 378(3), 293-301.
Abstract: In the present study, we aimed to determine whether cytidine-5'-diphosphatecholine (CDP-choline or citicoline) can improve the outcome of short-term myocardial ischemia-reperfusion injury in rats. Ischemia was produced in anesthetized rats by ligature of the left anterior descending coronary artery for 7 min followed by a reperfusion period of 7 min. Reperfusion-induced ventricular tachycardia (VT), ventricular fibrillation (VF), survival rate, and changes in arterial pressure were evaluated. Saline (1 ml/kg), CDP-choline (100, 250,and 500 mg/kg), or lidocaine (5 mg/kg) was intravenously injected in the middle of the ischemic period. Intracerebroventricular (i.c.v.) mecamylamine (50 mu g) or atropine sulfate (10 mu g) pretreatments were made 10 min before the coronary occlusion period. Pretreatment with intravenous (i.v.) atropine methylnitrate (2 and 5 mg/kg; i.v.) or bilateral vagotomy was performed 5 min before the induction of ischemia. An in vivo microdialysis study was performed in the nucleus ambiguus area (NA); choline and acetylcholine levels were measured in extracellular fluids. In control rats, VT, VF, and lethality were observed in 85%, 60% and 50% of the animals, respectively. Intravenous CDP-choline produced a short-term increase in blood pressure and reduced the incidence of VT, VF, and lethality dose-dependently when injected in the middle of the ischemic period. CDP-choline at doses of 250 and 500 mg/kg completely prevented death. Intracerebroventricular atropine sulfate pretreatment completely abolished the protective effect of CDP-choline, while mecamylamine pretreatment had no effect on the drug. CDP-choline increased the levels of extracellular choline and acetylcholine in the NA area. Bilateral vagotomy completely abolished the protective effect of CDP-choline in the reperfusion period. Moreover, the intravenous pretreatment with atropine methylnitrate produced dose-dependent blockade in the reduction of VT, VF, and mortality rates induced by CDP-choline. Neither of these pretreatments except mecamylamine affected the pressor effect of CDP-choline. Intracerebroventricular mecamylamine attenuated the increase in blood pressure induced by CDP-choline. In conclusion, intravenously injected CDP-choline prevents cardiac arrhythmias and death induced by short-term myocardial ischemia-reperfusion injury. Activation of central muscarinic receptors and vagal pathways mediates the protective effect of CDP-choline. The protective effect of CDP-choline is not related to its pressor effect.
URI: https://doi.org/10.1007/s00210-008-0300-0
https://link.springer.com/article/10.1007/s00210-008-0300-0
http://hdl.handle.net/11452/26010
ISSN: 0028-1298
1432-1912
Appears in Collections:PubMed
Scopus
Web of Science

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