PMID- 18504556
OWN - NLM
STAT- MEDLINE
DCOM- 20090116
LR  - 20211020
IS  - 0028-1298 (Print)
IS  - 0028-1298 (Linking)
VI  - 378
IP  - 3
DP  - 2008 Sep
TI  - CDP-choline prevents cardiac arrhythmias and lethality induced by short-term 
      myocardial ischemia-reperfusion injury in the rat: involvement of central 
      muscarinic cholinergic mechanisms.
PG  - 293-301
LID - 10.1007/s00210-008-0300-0 [doi]
AB  - 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 microg) or atropine sulfate (10 microg) 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.
FAU - Yilmaz, M Sertac
AU  - Yilmaz MS
AD  - Faculty of Medicine, Department of Pharmacology, Uludag University, Bursa, 
      Turkey.
FAU - Coskun, Cenk
AU  - Coskun C
FAU - Yalcin, Murat
AU  - Yalcin M
FAU - Savci, Vahide
AU  - Savci V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080527
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Nootropic Agents)
RN  - 0 (Receptors, Muscarinic)
RN  - 536BQ2JVC7 (Cytidine Diphosphate Choline)
RN  - 7C0697DR9I (Atropine)
RN  - N91BDP6H0X (Choline)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/metabolism
MH  - Anesthesia
MH  - Animals
MH  - *Anti-Arrhythmia Agents
MH  - Atropine/pharmacology
MH  - Blood Pressure/drug effects
MH  - Choline/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - Cytidine Diphosphate Choline/*pharmacology
MH  - Electrocardiography/drug effects
MH  - Injections, Intraventricular
MH  - Male
MH  - Microdialysis
MH  - Muscarinic Antagonists/pharmacology
MH  - Myocardial Reperfusion Injury/*complications
MH  - Nootropic Agents/*pharmacology
MH  - Rats
MH  - Receptors, Muscarinic/*drug effects
MH  - Survival Analysis
MH  - Vagotomy
EDAT- 2008/05/28 09:00
MHDA- 2009/01/17 09:00
CRDT- 2008/05/28 09:00
PHST- 2007/12/10 00:00 [received]
PHST- 2008/04/10 00:00 [accepted]
PHST- 2008/05/28 09:00 [pubmed]
PHST- 2009/01/17 09:00 [medline]
PHST- 2008/05/28 09:00 [entrez]
AID - 10.1007/s00210-008-0300-0 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2008 Sep;378(3):293-301. doi: 
      10.1007/s00210-008-0300-0. Epub 2008 May 27.