title: Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model.
abstract: BACKGROUND
  Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS) when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO) in a large animal model.
  
  
  METHODS
  A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9 mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was evaluated by ex vivo SPECT. IS and MO were evaluated by ex vivo MRI.
  
  
  RESULTS
  No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 +/- 4.2% vs 69.4 +/- 5.0%, p = NS) or MO (10.7 +/- 4.8% vs 11.4 +/- 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia.
  
  
  CONCLUSIONS
  Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.
authors.affiliation: Department of Cardiology, Lund University Hospital, Lund, Sweden.
authors.forename: Jesper
authors.initials: J
authors.lastname: van der Pals
authors.forename: Sasha
authors.initials: S
authors.lastname: Koul
authors.forename: Michael I
authors.initials: MI
authors.lastname: Götberg
authors.forename: Göran K
authors.initials: GK
authors.lastname: Olivecrona
authors.forename: Martin
authors.initials: M
authors.lastname: Ugander
authors.forename: Mikael
authors.initials: M
authors.lastname: Kanski
authors.forename: Andreas
authors.initials: A
authors.lastname: Otto
authors.forename: Matthias
authors.initials: M
authors.lastname: Götberg
authors.forename: Håkan
authors.initials: H
authors.lastname: Arheden
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
mesh_terms: D000818:Animals; D001081:Apyrase / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D011897:Random Allocation; D013552:Swine
chemical_list: D001081:Apyrase