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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 isch...

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Autores principales: van der Pals, Jesper, Koul, Sasha, Götberg, Michael I, Olivecrona, Göran K, Ugander, Martin, Kanski, Mikael, Otto, Andreas, Götberg, Matthias, Arheden, Håkan, Erlinge, David
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820435/
https://www.ncbi.nlm.nih.gov/pubmed/20047685
http://dx.doi.org/10.1186/1471-2261-10-1
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author van der Pals, Jesper
Koul, Sasha
Götberg, Michael I
Olivecrona, Göran K
Ugander, Martin
Kanski, Mikael
Otto, Andreas
Götberg, Matthias
Arheden, Håkan
Erlinge, David
author_facet van der Pals, Jesper
Koul, Sasha
Götberg, Michael I
Olivecrona, Göran K
Ugander, Martin
Kanski, Mikael
Otto, Andreas
Götberg, Matthias
Arheden, Håkan
Erlinge, David
author_sort van der Pals, Jesper
collection PubMed
description 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.
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spelling pubmed-28204352010-02-12 Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model van der Pals, Jesper Koul, Sasha Götberg, Michael I Olivecrona, Göran K Ugander, Martin Kanski, Mikael Otto, Andreas Götberg, Matthias Arheden, Håkan Erlinge, David BMC Cardiovasc Disord Research article 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. BioMed Central 2010-01-04 /pmc/articles/PMC2820435/ /pubmed/20047685 http://dx.doi.org/10.1186/1471-2261-10-1 Text en Copyright ©2010 van der Pals et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research article
van der Pals, Jesper
Koul, Sasha
Götberg, Michael I
Olivecrona, Göran K
Ugander, Martin
Kanski, Mikael
Otto, Andreas
Götberg, Matthias
Arheden, Håkan
Erlinge, David
Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model
title Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model
title_full Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model
title_fullStr Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model
title_full_unstemmed Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model
title_short Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model
title_sort apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model
topic Research article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820435/
https://www.ncbi.nlm.nih.gov/pubmed/20047685
http://dx.doi.org/10.1186/1471-2261-10-1
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