Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model
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 (40-50kg). 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.
Author: Jesper van der PalsSasha KoulMichael GotbergGoran OlivecronaMartin UganderMikael KanskiAndreas OttoMatthias GotbergHakan ArhedenDavid Erlinge
Credits/Source: BMC Cardiovascular Disorders 2010, 10:1
Published on: 2010-01-04
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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