Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model

作者：van der Pals Jesper; Koul Sasha; Gotberg Michael I; Olivecrona Goran K; Ugander Martin; Kanski Mikael; Otto Andreas; Gotberg Matthias; Arheden Hakan; Erlinge David^*

来源：BMC Cardiovascular Disorders, 2010, 10: 1.

DOI：10.1186/1471-2261-10-1

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.
Conclusion: 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.

• 出版日期2010-1-4