TY - JOUR
T1 - Mirabegron, a Clinically Approved β3 Adrenergic Receptor Agonist, Does Not Reduce Infarct Size in a Swine Model of Reperfused Myocardial Infarction
AU - Rossello, Xavier
AU - Piñero, Antonio
AU - Fernández-Jiménez, Rodrigo
AU - Sánchez-González, Javier
AU - Pizarro, Gonzalo
AU - Galán-Arriola, Carlos
AU - Lobo-Gonzalez, Manuel
AU - Vilchez, Jean Paul
AU - García-Prieto, Jaime
AU - García-Ruiz, Jose Manuel
AU - García-Álvarez, Ana
AU - Sanz-Rosa, David
AU - Ibanez, Borja
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
KW - Acute myocardial infarction
KW - Cardioprotection
KW - Ischemia/reperfusion injury
KW - Mirabegron
KW - Translational models
KW - β3 adrenergic receptor
UR - http://www.scopus.com/inward/record.url?scp=85051627040&partnerID=8YFLogxK
U2 - 10.1007/s12265-018-9819-8
DO - 10.1007/s12265-018-9819-8
M3 - Article
C2 - 30073540
AN - SCOPUS:85051627040
SN - 1937-5387
VL - 11
SP - 310
EP - 318
JO - Journal of Cardiovascular Translational Research
JF - Journal of Cardiovascular Translational Research
IS - 4
ER -