title: Protective effect of CDP-choline on ischemia-reperfusion-induced myocardial tissue injury in rats.
abstract: BACKGROUND
  CDP-choline exerts tissue protective effect in several ischemic conditions. Recently we have reported that the drug prevents cardiac arrhythmias and improves survival rate in short-term myocardial ischemia reperfusion in rats.
  
  
  OBJECTIVE
  In the current study, we determined the effect of intravenously administered CDP-choline on myocardial tissue injury induced by 30-min ischemia followed by 3-h reperfusion in anesthetized rats.
  
  
  METHODS
  Myocardial ischemia was produced by ligature of the left main coronary artery. CDP-choline (100-500 mg/kg) was intravenously injected in the middle of the ischemic period. Cardiovascular parameters were recorded through the experimental period. At the end of the reperfusion period, the hearts of the animals were removed and stained for the investigation of tissue necrosis and apoptosis. The infarct size was evaluated as the ratio of the infarct area to the risk area. Apoptotic activation was assessed by TUNEL assay. Also the blood samples of rats were collected for the measurement of M30-M65, ADMA, homocysteine, and lactate levels.
  
  
  RESULTS
  Ischemia/reperfusion caused serious injury in myocardium, increased blood ADMA and lactate levels without influencing other parameters. CDP-choline significantly reduced the infarct size and the number of apoptotic cells in the risk area. Blood pressure increased after CDP-choline injection; however, it returned back to the basal levels before the onset of reperfusion. CDP-choline failed to alter any other measured parameters.
  
  
  CONCLUSIONS
  The present results demonstrate that intravenously administered CDP-choline is able to protect myocardium from injury induced by long-term coronary occlusion-reperfusion in rats. The inhibition of apoptosis by the drug may contribute to its protective effect. But neither the increase in blood pressure in response to CDP-choline injection nor changes in plasma ADMA concentration appear to mediate the attenuation of the myocardial injury.
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Uludag University, 16059, Bursa, Turkey.
authors.forename: C
authors.initials: C
authors.lastname: Coskun
authors.forename: B
authors.initials: B
authors.lastname: Avci
authors.forename: M
authors.initials: M
authors.lastname: Yalcin
authors.forename: A
authors.initials: A
authors.lastname: Yermezler
authors.forename: M S
authors.initials: MS
authors.lastname: Yilmaz
authors.forename: V
authors.initials: V
authors.lastname: Savci
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001794:Blood Pressure; D003566:Cytidine Diphosphate Choline / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar
chemical_list: C487735:dimethylarginine; D006710:Homocysteine; D019344:Lactic Acid; D003566:Cytidine Diphosphate Choline; D001120:Arginine