Mirabegron, a Clinically Approved β3 Adrenergic Receptor Agonist, Does Not Reduce Infarct Size in a Swine Model of Reperfused Myocardial Infarction

Xavier Rossello, Antonio Piñero, Rodrigo Fernández-Jiménez, Javier Sánchez-González, Gonzalo Pizarro, Carlos Galán-Arriola, Manuel Lobo-Gonzalez, Jean Paul Vilchez, Jaime García-Prieto, Jose Manuel García-Ruiz, Ana García-Álvarez, David Sanz-Rosa, Borja Ibanez

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The administration of the selective β3 adrenergic receptor (β3AR) agonist BRL-37344 protects from myocardial ischemia/reperfusion injury (IRI), although the lack of clinical approval limits its translatability. We tested the cardioprotective effect of mirabegron, the first-in-class β3AR agonist approved for human use. A dose-response study was conducted in 6 pigs to select the highest intravenous dose of mirabegron without significant detrimental hemodynamic effect. Subsequently, closed chest anterior myocardial infarction (45 min ischemia followed by reperfusion) was performed in 26 pigs which randomly received either mirabegron (10 μg/kg) or placebo 5 min before reperfusion. Day-7 cardiac magnetic resonance (CMR) showed no differences in infarct size (35.0 ± 2.0% of left ventricle (LV) vs. 35.9 ± 2.4% in mirabegron and placebo respectively, p = 0.782) or LV ejection fraction (36.3 ± 1.1 vs. 34.6 ± 1.9%, p = 0.430). Consistent results were obtained on day-45 CMR. In conclusion, the intravenous administration of the clinically available selective β3AR agonist mirabegron does not reduce infarct size in a swine model of IRI.

Original languageEnglish
Pages (from-to)310-318
Number of pages9
JournalJournal of Cardiovascular Translational Research
Volume11
Issue number4
DOIs
StatePublished - 1 Aug 2018

Keywords

  • Acute myocardial infarction
  • Cardioprotection
  • Ischemia/reperfusion injury
  • Mirabegron
  • Translational models
  • β3 adrenergic receptor

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