Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model.
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.
van der Pals
Jesper
J
Department of Cardiology, Lund University Hospital, Lund, Sweden.
Koul
Sasha
S
Götberg
Michael I
MI
Olivecrona
Göran K
GK
Ugander
Martin
M
Kanski
Mikael
M
Otto
Andreas
A
Götberg
Matthias
M
Arheden
Håkan
H
Erlinge
David
D
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
D001081:Apyrase