A tale of pigs, beta-blockers and genetic variants

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Zurück zum Zitat Botker HE, Hausenloy D, Andreadou I, Antonucci S, Boengler K, Davidson SM, Deshwal S, Devaux Y, Di Lisa F, Di Sante M, Efentakis P, Femmino S, Garcia-Dorado D, Giricz Z, Ibanez B, Iliodromitis E, Kaludercic N, Kleinbongard P, Neuhauser M, Ovize M, Pagliaro P, Rahbek-Schmidt M, Ruiz-Meana M, Schluter KD, Schulz R, Skyschally A, Wilder C, Yellon DM, Ferdinandy P, Heusch G (2018) Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. Basic Res Cardiol 113:39. https://doi.org/10.1007/s00395-018-0696-8CrossRefPubMedPubMedCentral Botker HE, Hausenloy D, Andreadou I, Antonucci S, Boengler K, Davidson SM, Deshwal S, Devaux Y, Di Lisa F, Di Sante M, Efentakis P, Femmino S, Garcia-Dorado D, Giricz Z, Ibanez B, Iliodromitis E, Kaludercic N, Kleinbongard P, Neuhauser M, Ovize M, Pagliaro P, Rahbek-Schmidt M, Ruiz-Meana M, Schluter KD, Schulz R, Skyschally A, Wilder C, Yellon DM, Ferdinandy P, Heusch G (2018) Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. Basic Res Cardiol 113:39. https://​doi.​org/​10.​1007/​s00395-018-0696-8CrossRefPubMedPubMedCentral

Zurück zum Zitat Clemente-Moragon A, Gomez M, Villena-Gutierrez R, Lalama DV, Garcia-Prieto J, Martinez F, Sanchez-Cabo F, Fuster V, Oliver E, Ibanez B (2020) Metoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation. Eur Heart J 41:4425–4440. https://doi.org/10.1093/eurheartj/ehaa733CrossRefPubMedPubMedCentral Clemente-Moragon A, Gomez M, Villena-Gutierrez R, Lalama DV, Garcia-Prieto J, Martinez F, Sanchez-Cabo F, Fuster V, Oliver E, Ibanez B (2020) Metoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation. Eur Heart J 41:4425–4440. https://​doi.​org/​10.​1093/​eurheartj/​ehaa733CrossRefPubMedPubMedCentral

Zurück zum Zitat Clemente-Moragon A, Martinez-Milla J, Oliver E, Santos A, Flandes J, Fernandez I, Rodriguez-Gonzalez L, Serrano Del Castillo C, Ioan AM, Lopez-Alvarez M, Gomez-Talavera S, Galan-Arriola C, Fuster V, Perez-Calvo C, Ibanez B (2021) Metoprolol in critically Ill patients with COVID-19. J Am Coll Cardiol 78:1001–1011. https://doi.org/10.1016/j.jacc.2021.07.003CrossRefPubMedPubMedCentral Clemente-Moragon A, Martinez-Milla J, Oliver E, Santos A, Flandes J, Fernandez I, Rodriguez-Gonzalez L, Serrano Del Castillo C, Ioan AM, Lopez-Alvarez M, Gomez-Talavera S, Galan-Arriola C, Fuster V, Perez-Calvo C, Ibanez B (2021) Metoprolol in critically Ill patients with COVID-19. J Am Coll Cardiol 78:1001–1011. https://​doi.​org/​10.​1016/​j.​jacc.​2021.​07.​003CrossRefPubMedPubMedCentral

Zurück zum Zitat Clemente-Moragon A, Oliver E, Calle D, Cusso L, Gomez M, Pradillo JM, Castejon R, Rallon N, Benito JM, Fernandez-Ferro JC, Carneado-Ruiz J, Moro MA, Sanchez-Gonzalez J, Fuster V, Cortes-Canteli M, Desco M, Ibanez B (2023) Neutrophil beta(1) adrenoceptor blockade blunts stroke-associated neuroinflammation. Br J Pharmacol 180:459–478. https://doi.org/10.1111/bph.15963CrossRefPubMed Clemente-Moragon A, Oliver E, Calle D, Cusso L, Gomez M, Pradillo JM, Castejon R, Rallon N, Benito JM, Fernandez-Ferro JC, Carneado-Ruiz J, Moro MA, Sanchez-Gonzalez J, Fuster V, Cortes-Canteli M, Desco M, Ibanez B (2023) Neutrophil beta(1) adrenoceptor blockade blunts stroke-associated neuroinflammation. Br J Pharmacol 180:459–478. https://​doi.​org/​10.​1111/​bph.​15963CrossRefPubMed

Zurück zum Zitat Ferdinandy P, Andreadou I, Baxter GF, Botker HE, Davidson SM, Dobrev D, Gersh BJ, Heusch G, Lecour S, Ruiz-Meana M, Zuurbier CJ, Hausenloy DJ, Schulz R (2023) Interaction of cardiovascular nonmodifiable risk factors, comorbidities and comedications with ischemia/reperfusion injury and cardioprotection by pharmacological treatments and ischemic conditioning. Pharmacol Rev 75:159–216. https://doi.org/10.1124/pharmrev.121.000348CrossRefPubMedPubMedCentral Ferdinandy P, Andreadou I, Baxter GF, Botker HE, Davidson SM, Dobrev D, Gersh BJ, Heusch G, Lecour S, Ruiz-Meana M, Zuurbier CJ, Hausenloy DJ, Schulz R (2023) Interaction of cardiovascular nonmodifiable risk factors, comorbidities and comedications with ischemia/reperfusion injury and cardioprotection by pharmacological treatments and ischemic conditioning. Pharmacol Rev 75:159–216. https://​doi.​org/​10.​1124/​pharmrev.​121.​000348CrossRefPubMedPubMedCentral

Zurück zum Zitat Garcia-Prieto J, Villena-Gutierrez R, Gomez M, Bernardo E, Pun-Garcia A, Garcia-Lunar I, Crainiciuc G, Fernandez-Jimenez R, Sreeramkumar V, Bourio-Martinez R, Garcia-Ruiz JM, Del Valle AS, Sanz-Rosa D, Pizarro G, Fernandez-Ortiz A, Hidalgo A, Fuster V, Ibanez B (2017) Neutrophil stunning by metoprolol reduces infarct size. Nat Commun 8:14780. https://doi.org/10.1038/ncomms14780CrossRefPubMedPubMedCentral Garcia-Prieto J, Villena-Gutierrez R, Gomez M, Bernardo E, Pun-Garcia A, Garcia-Lunar I, Crainiciuc G, Fernandez-Jimenez R, Sreeramkumar V, Bourio-Martinez R, Garcia-Ruiz JM, Del Valle AS, Sanz-Rosa D, Pizarro G, Fernandez-Ortiz A, Hidalgo A, Fuster V, Ibanez B (2017) Neutrophil stunning by metoprolol reduces infarct size. Nat Commun 8:14780. https://​doi.​org/​10.​1038/​ncomms14780CrossRefPubMedPubMedCentral

Zurück zum Zitat Garcia-Ruiz JM, Fernandez-Jimenez R, Garcia-Alvarez A, Pizarro G, Galan-Arriola C, Fernandez-Friera L, Mateos A, Nuno-Ayala M, Aguero J, Sanchez-Gonzalez J, Garcia-Prieto J, Lopez-Melgar B, Martinez-Tenorio P, Lopez-Martin GJ, Macias A, Perez-Asenjo B, Cabrera JA, Fernandez-Ortiz A, Fuster V, Ibanez B (2016) Impact of the timing of metoprolol administration during STEMI on infarct size and ventricular function. J Am Coll Cardiol 67:2093–2104. https://doi.org/10.1016/j.jacc.2016.02.050CrossRefPubMed Garcia-Ruiz JM, Fernandez-Jimenez R, Garcia-Alvarez A, Pizarro G, Galan-Arriola C, Fernandez-Friera L, Mateos A, Nuno-Ayala M, Aguero J, Sanchez-Gonzalez J, Garcia-Prieto J, Lopez-Melgar B, Martinez-Tenorio P, Lopez-Martin GJ, Macias A, Perez-Asenjo B, Cabrera JA, Fernandez-Ortiz A, Fuster V, Ibanez B (2016) Impact of the timing of metoprolol administration during STEMI on infarct size and ventricular function. J Am Coll Cardiol 67:2093–2104. https://​doi.​org/​10.​1016/​j.​jacc.​2016.​02.​050CrossRefPubMed

Zurück zum Zitat Heusch G, Gersh BJ (2020) Is cardioprotection salvageable? Circulation 141:415–417. https://doi.org/10.1161/CIRCULATIONAHA.119.044176CrossRefPubMed Heusch G, Gersh BJ (2020) Is cardioprotection salvageable? Circulation 141:415–417. https://​doi.​org/​10.​1161/​CIRCULATIONAHA.​119.​044176CrossRefPubMed

Zurück zum Zitat Heusch G, Kleinbongard P (2020) Is metoprolol more cardioprotective than other beta-blockers? Eur Heart J 41:4441–4443. https://doi.org/10.1093/eurheartj/ehaa764CrossRefPubMed Heusch G, Kleinbongard P (2020) Is metoprolol more cardioprotective than other beta-blockers? Eur Heart J 41:4441–4443. https://​doi.​org/​10.​1093/​eurheartj/​ehaa764CrossRefPubMed

Zurück zum Zitat Ibanez B (2020) Intravenous beta-blockers in STEMI: what you are about to do, do it quickly. Eur Heart J Acute Cardiovasc Care 9:459–461. https://doi.org/10.1177/2048872620950205CrossRefPubMed Ibanez B (2020) Intravenous beta-blockers in STEMI: what you are about to do, do it quickly. Eur Heart J Acute Cardiovasc Care 9:459–461. https://​doi.​org/​10.​1177/​2048872620950205​CrossRefPubMed

Zurück zum Zitat Ibanez B (2022) Targeting inflammation to improve long-term outcome in ST-segment elevation myocardial infarction survivors. Eur Heart J Acute Cardiovasc Care 11:124–126. https://doi.org/10.1093/ehjacc/zuac002CrossRefPubMed Ibanez B (2022) Targeting inflammation to improve long-term outcome in ST-segment elevation myocardial infarction survivors. Eur Heart J Acute Cardiovasc Care 11:124–126. https://​doi.​org/​10.​1093/​ehjacc/​zuac002CrossRefPubMed

Zurück zum Zitat Ibanez B, Prat-Gonzalez S, Speidl WS, Vilahur G, Pinero A, Cimmino G, Garcia MJ, Fuster V, Sanz J, Badimon JJ (2007) Early metoprolol administration before coronary reperfusion results in increased myocardial salvage: analysis of ischemic myocardium at risk using cardiac magnetic resonance. Circulation 115:2909–2916. https://doi.org/10.1161/CIRCULATIONAHA.106.679639CrossRefPubMed Ibanez B, Prat-Gonzalez S, Speidl WS, Vilahur G, Pinero A, Cimmino G, Garcia MJ, Fuster V, Sanz J, Badimon JJ (2007) Early metoprolol administration before coronary reperfusion results in increased myocardial salvage: analysis of ischemic myocardium at risk using cardiac magnetic resonance. Circulation 115:2909–2916. https://​doi.​org/​10.​1161/​CIRCULATIONAHA.​106.​679639CrossRefPubMed

Zurück zum Zitat Ibanez B, Macaya C, Sanchez-Brunete V, Pizarro G, Fernandez-Friera L, Mateos A, Fernandez-Ortiz A, Garcia-Ruiz JM, Garcia-Alvarez A, Iniguez A, Jimenez-Borreguero J, Lopez-Romero P, Fernandez-Jimenez R, Goicolea J, Ruiz-Mateos B, Bastante T, Arias M, Iglesias-Vazquez JA, Rodriguez MD, Escalera N, Acebal C, Cabrera JA, Valenciano J, Perez de Prado A, Fernandez-Campos MJ, Casado I, Garcia-Rubira JC, Garcia-Prieto J, Sanz-Rosa D, Cuellas C, Hernandez-Antolin R, Albarran A, Fernandez-Vazquez F, de la Torre-Hernandez JM, Pocock S, Sanz G, Fuster V (2013) Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the effect of metoprolol in cardioprotection during an acute myocardial infarction (METOCARD-CNIC) trial. Circulation 128:1495–1503. https://doi.org/10.1161/CIRCULATIONAHA.113.003653CrossRefPubMed Ibanez B, Macaya C, Sanchez-Brunete V, Pizarro G, Fernandez-Friera L, Mateos A, Fernandez-Ortiz A, Garcia-Ruiz JM, Garcia-Alvarez A, Iniguez A, Jimenez-Borreguero J, Lopez-Romero P, Fernandez-Jimenez R, Goicolea J, Ruiz-Mateos B, Bastante T, Arias M, Iglesias-Vazquez JA, Rodriguez MD, Escalera N, Acebal C, Cabrera JA, Valenciano J, Perez de Prado A, Fernandez-Campos MJ, Casado I, Garcia-Rubira JC, Garcia-Prieto J, Sanz-Rosa D, Cuellas C, Hernandez-Antolin R, Albarran A, Fernandez-Vazquez F, de la Torre-Hernandez JM, Pocock S, Sanz G, Fuster V (2013) Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the effect of metoprolol in cardioprotection during an acute myocardial infarction (METOCARD-CNIC) trial. Circulation 128:1495–1503. https://​doi.​org/​10.​1161/​CIRCULATIONAHA.​113.​003653CrossRefPubMed

Zurück zum Zitat Ibanez B, Heusch G, Ovize M, Van de Werf F (2015) Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol 65:1454–1471. https://doi.org/10.1016/j.jacc.2015.02.032CrossRefPubMed Ibanez B, Heusch G, Ovize M, Van de Werf F (2015) Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol 65:1454–1471. https://​doi.​org/​10.​1016/​j.​jacc.​2015.​02.​032CrossRefPubMed

Zurück zum Zitat Ibanez B, Aletras AH, Arai AE, Arheden H, Bax J, Berry C, Bucciarelli-Ducci C, Croisille P, Dall’Armellina E, Dharmakumar R, Eitel I, Fernandez-Jimenez R, Friedrich MG, Garcia-Dorado D, Hausenloy DJ, Kim RJ, Kozerke S, Kramer CM, Salerno M, Sanchez-Gonzalez J, Sanz J, Fuster V (2019) Cardiac MRI endpoints in myocardial infarction experimental and clinical trials: JACC scientific expert Panel. J Am Coll Cardiol 74:238–256. https://doi.org/10.1016/j.jacc.2019.05.024CrossRefPubMedPubMedCentral Ibanez B, Aletras AH, Arai AE, Arheden H, Bax J, Berry C, Bucciarelli-Ducci C, Croisille P, Dall’Armellina E, Dharmakumar R, Eitel I, Fernandez-Jimenez R, Friedrich MG, Garcia-Dorado D, Hausenloy DJ, Kim RJ, Kozerke S, Kramer CM, Salerno M, Sanchez-Gonzalez J, Sanz J, Fuster V (2019) Cardiac MRI endpoints in myocardial infarction experimental and clinical trials: JACC scientific expert Panel. J Am Coll Cardiol 74:238–256. https://​doi.​org/​10.​1016/​j.​jacc.​2019.​05.​024CrossRefPubMedPubMedCentral

Zurück zum Zitat Kleinbongard P, Lieder HR, Skyschally A, Heusch G (2023) No robust reduction of infarct size and no-reflow by metoprolol pretreatment in adult Gottingen minipigs. Basic Res Cardiol 118:23. https://doi.org/10.1007/s00395-023-00993-4CrossRefPubMedPubMedCentral Kleinbongard P, Lieder HR, Skyschally A, Heusch G (2023) No robust reduction of infarct size and no-reflow by metoprolol pretreatment in adult Gottingen minipigs. Basic Res Cardiol 118:23. https://​doi.​org/​10.​1007/​s00395-023-00993-4CrossRefPubMedPubMedCentral

Zurück zum Zitat Lecour S, Andreadou I, Botker HE, Davidson SM, Heusch G, Ruiz-Meana M, Schulz R, Zuurbier CJ, Ferdinandy P, Hausenloy DJ, on behalf of the European Union CCAC (2021) IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria: guidelines of the EU-CARDIOPROTECTION COST action. Basic Res Cardiol 116:52. https://doi.org/10.1007/s00395-021-00893-5CrossRefPubMedPubMedCentral Lecour S, Andreadou I, Botker HE, Davidson SM, Heusch G, Ruiz-Meana M, Schulz R, Zuurbier CJ, Ferdinandy P, Hausenloy DJ, on behalf of the European Union CCAC (2021) IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria: guidelines of the EU-CARDIOPROTECTION COST action. Basic Res Cardiol 116:52. https://​doi.​org/​10.​1007/​s00395-021-00893-5CrossRefPubMedPubMedCentral

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