title: The cardioprotective efficacy of TVP1022 in a rat model of ischaemia/reperfusion.
abstract: OBJECTIVE
  Because myocardial infarction is a major cause of morbidity and mortality worldwide, protecting the heart from the ischaemia and reperfusion (I/R) damage is the focus of intense research. Based on our in vitro findings showing that TVP1022 (the S-enantiomer of rasagiline, an anti-Parkinsonian drug) possesses cardioprotective effects, in the present study we investigated the hypothesis that TVP1022 can attenuate myocardial damage in an I/R model in rats.
  
  
  METHODS
  The model consisted of 30-min occlusion of the left anterior descending artery followed by 4 or 24 h reperfusion. In addition, we investigated the possible mechanisms of cardioprotection in H9c2 cells and neonatal rat ventricular myocytes (NRVM) exposed to oxidative stress induced by H(2) O(2) .
  
  
  RESULTS
  TVP1022 (20 and 40 mg·kg(-1) ) administered 5 min before reperfusion followed by an additional dose 4 h after reperfusion reduced the infarct size and attenuated the decline in ventricular function. TVP1022 also attenuated I/R-induced deterioration in cardiac mitochondrial integrity evaluated by mitochondrial swelling capacity. In vitro, using H9c2 cells and NRVM, TVP1022 attenuated both serum free- and H(2) O(2) -induced damage, preserved mitochondrial membrane potential and Bcl-2 levels, inhibited mitochondrial cytochrome c release and the increase in cleaved caspase 9 and 3 levels, and enhanced the phosphorylation of protein kinase C and glycogen synthase kinase-3β.
  
  
  CONCLUSIONS
  TVP1022 provided cardioprotection in a model of myocardial infarction, and therefore should be considered as a novel adjunctive therapy for attenuating myocardial damage resulting from I/R injuries.
authors.affiliation: Department of Physiology, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Offir
authors.initials: O
authors.lastname: Ertracht
authors.forename: Esti
authors.initials: E
authors.lastname: Liani
authors.forename: Noa
authors.initials: N
authors.lastname: Bachner-Hinenzon
authors.forename: Orit
authors.initials: O
authors.lastname: Bar-Am
authors.forename: Luba
authors.initials: L
authors.lastname: Frolov
authors.forename: Elena
authors.initials: E
authors.lastname: Ovcharenko
authors.forename: Huda
authors.initials: H
authors.lastname: Awad
authors.forename: Shany
authors.initials: S
authors.lastname: Blum
authors.forename: Yaron
authors.initials: Y
authors.lastname: Barac
authors.forename: Tamar
authors.initials: T
authors.lastname: Amit
authors.forename: Dan
authors.initials: D
authors.lastname: Adam
authors.forename: Moussa
authors.initials: M
authors.lastname: Youdim
authors.forename: Ofer
authors.initials: O
authors.lastname: Binah
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D002316:Cardiotonic Agents; D007189:Indans; D019253:Proto-Oncogene Proteins c-bcl-2; C031967:rasagiline; D045304:Cytochromes c; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3; D053453:Caspase 9