2026-05-07T11:03:33Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/125422024-09-27T08:00:54Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Clemente-Moragón, Agustín
author
Gomez, Monica
author
Villena-Gutierrez, Rocio
author
Lalama, Doménica V
author
Garcia-Prieto, Jaime
author
Martinez, Fernando
author
Sanchez-Cabo, Fatima
author
Fuster, Valentin
author
Oliver, Eduardo
author
Ibáñez, Borja
funder
Ministerio de Ciencia e Innovación (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Comunidad de Madrid (España)
funder
Fundación ProCNIC
2021-04-07T09:54:46Z
2021-04-07T09:54:46Z
2020-12
Eur Heart J. 2020; 41(46):4425-4440
10.1093/eurheartj/ehaa733
1522-9645
European heart journal
33026079
http://hdl.handle.net/20.500.12105/12542
Clinical guidelines recommend early intravenous β-blockers during ongoing myocardial infarction; however, it is unknown whether all β-blockers exert a similar cardioprotective effect. We experimentally compared three clinically approved intravenous β-blockers. Mice undergoing 45 min/24 h ischaemia-reperfusion (I/R) received vehicle, metoprolol, atenolol, or propranolol at min 35. The effect on neutrophil infiltration was tested in three models of exacerbated inflammation. Neutrophil migration was evaluated in vitro and in vivo by intravital microscopy. The effect of β-blockers on the conformation of the β1 adrenergic receptor was studied in silico. Of the tested β-blockers, only metoprolol ameliorated I/R injury [infarct size (IS) = 18.0% ± 0.03% for metoprolol vs. 35.9% ± 0.03% for vehicle; P < 0.01]. Atenolol and propranolol had no effect on IS. In the three exacerbated inflammation models, neutrophil infiltration was significantly attenuated only in the presence of metoprolol (60%, 50%, and 70% reductions vs. vehicle in myocardial I/R injury, thioglycolate-induced peritonitis, and lipopolysaccharide-induced acute lung injury, respectively). Migration studies confirmed the particular ability of metoprolol to disrupt neutrophil dynamics. In silico analysis indicated different intracellular β1 adrenergic receptor conformational changes when bound to metoprolol than to the other two β-blockers. Metoprolol exerts a disruptive action on neutrophil dynamics during exacerbated inflammation, resulting in an infarct-limiting effect not observed with atenolol or propranolol. The differential effect of β-blockers may be related to distinct conformational changes in the β1 adrenergic receptor upon metoprolol binding. If these data are confirmed in a clinical trial, metoprolol should become the intravenous β-blocker of choice for patients with ongoing infarction.
eng
Metoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation.
journal article
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MetoprololExertsANon-class_2020.pdf
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ehaa733_supplementary_data.pdf
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MetoprololExertsANon-class_2020.pdf.txt
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ehaa733_supplementary_data.pdf.txt