Related Experiment Video
Updated: Dec 6, 2025
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
Metoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation
Agustín Clemente-Moragón1, Mónica Gómez1, Rocío Villena-Gutiérrez1
1Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain.
Aims:
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.
Methods And Results:
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.
Conclusions:
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.
Insights
Metoprolol, unlike atenolol and propranolol, limits infarct size by disrupting neutrophil dynamics during myocardial infarction. This suggests metoprolol may be the preferred intravenous beta-blocker for treating heart attacks.
Area of Science:
- Cardiovascular Pharmacology
- Myocardial Ischemia-Reperfusion Injury
- Inflammation and Immunology
Background:
- Clinical guidelines advocate early intravenous beta-blockers for acute myocardial infarction.
- The differential cardioprotective effects of various beta-blockers are not well-established.
- Understanding these differences is crucial for optimizing treatment strategies.
Purpose of the Study:
- To experimentally compare the cardioprotective effects of three intravenous beta-blockers: metoprolol, atenolol, and propranolol.
- To investigate the impact of these beta-blockers on neutrophil infiltration and migration in models of myocardial injury and inflammation.
- To explore the molecular mechanisms underlying potential differential effects, including beta-1 adrenergic receptor conformation.
Main Methods:
- A mouse model of myocardial ischemia-reperfusion (I/R) injury was employed.
- Beta-blockers (metoprolol, atenolol, propranolol) or vehicle were administered during reperfusion.
- Neutrophil infiltration was assessed in myocardial I/R and other inflammation models (peritonitis, ALI). In vitro and in vivo migration studies and in silico receptor binding analyses were performed.
Main Results:
- Only metoprolol significantly reduced infarct size (IS) in the I/R model compared to vehicle.
- Atenolol and propranolol did not affect infarct size.
- Metoprolol markedly attenuated neutrophil infiltration in myocardial I/R, peritonitis, and acute lung injury models.
- Metoprolol demonstrated a unique ability to disrupt neutrophil migration dynamics.
- In silico analysis revealed distinct conformational changes in the beta-1 adrenergic receptor upon binding with metoprolol compared to atenolol and propranolol.
Conclusions:
- Metoprolol exhibits a unique disruptive effect on neutrophil dynamics, leading to infarct limitation not seen with atenolol or propranolol.
- These differential effects are potentially linked to distinct beta-1 adrenergic receptor conformational changes induced by metoprolol.
- Metoprolol warrants consideration as the intravenous beta-blocker of choice for patients with acute myocardial infarction, pending clinical validation.
Related Concept Videos
01:31Adrenergic Antagonists: ɑ and β-Receptor Blockers
01:27Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:28Antihypertensive Drugs: Types of β-Blockers
01:16Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow....
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...