title: Dipeptidyl peptidase-4 inhibitor reduces infarct size and preserves cardiac function via mitochondrial protection in ischaemia-reperfusion rat heart.
abstract: OBJECTIVE
  We hypothesized that dipeptidyl peptidase (DPP)-4 inhibitor (vildagliptin) reduces fatal arrhythmias, cardiac dysfunction and infarct size caused by ischaemia-reperfusion (I/R) injury via its attenuation of cardiac mitochondrial dysfunction.
  
  
  METHODS
  In total, 26 rats were randomized to receive either 1 mL normal saline solution or 2.0 mg/kg vildagliptin intravenously (n = 13/group) 30 min prior to a 30-min left anterior descending coronary artery occlusion, followed by a 120-min reperfusion. Arrhythmia scores, cardiac functions, infarct size and mitochondrial function were evaluated.
  
  
  RESULTS
  Vildagliptin reduced the infarct size by 44% and mitigated cardiac dysfunction by preserving cardiac function without altering the incidence of cardiac arrhythmias. Vildagliptin increased expression of Bcl-2 and pro-caspase3 in the ischaemic area, whereas Bax and phosphorylated-connexin43/total-connexin43 were not altered. Vildagliptin attenuated cardiac mitochondrial dysfunction by reducing the reactive oxygen species level and mitochondrial swelling.
  
  
  CONCLUSIONS
  DPP-4 inhibitor provides cardioprotection by reducing the infarct size and ameliorating cardiac dysfunction in I/R hearts by attenuating cardiac mitochondrial dysfunction and cardiomyocyte apoptosis.
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Kroekkiat
authors.initials: K
authors.lastname: Chinda
authors.forename: Jantira
authors.initials: J
authors.lastname: Sanit
authors.forename: Siriporn
authors.initials: S
authors.lastname: Chattipakorn
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D009570:Nitriles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077597:Vildagliptin
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; D000218:Adamantane
keywords: Dipeptidyl peptidase-4 inhibitor; cardiac arrhythmia; ischaemia–reperfusion; mitochondria; myocardial infarction