A new mechanism of action for metoprolol may help explain how it can lessen the damage that occurs during a heart attack if given early, researchers from Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) reported. Full findings from the study are published in Nature Communications.
Metoprolol, a beta-1 adrenergic receptor antagonist, is currently indicated for the management of angina, for mortality reduction in stabilized patients after myocardial infarction (MI), for heart failure, and for hypertension.
The study authors discovered that rapid administration of metoprolol during a myocardial infarction directly inhibited the inflammatory action of neutrophils, resulting in a smaller area of tissue that is damaged post-infarct. Previously, metoprolol was perceived as acting primarily on cardiomyocytes. But the recent METOCARD-CNIC study (n=220) demonstrated that the drug reduced reperfusion injury by targeting the hematopoietic compartment.
Patients with acute myocardial infarction (AMI) were randomized to receive intravenous (IV) metoprolol 15mg or control pre-reperfusion. All patients underwent a cardiac magnetic resonance imaging exam one week post-AMI to determine the extent of microvascular obstruction (MVO), a key contributor to ischemia/reperfusion injury and infarct size.
The data showed patients treated with metoprolol during AMI had a 40% reduced extent of MVO. Moreover, patients treated with metoprolol had a 24% reduced infarct-normalized MVO vs. control patients. MVO was significantly associated with a poorer prognosis as measured by ventricualr performance. This led authors to believe that MVO reduction may be involved in the cardioprotective benefit of metoprolol given to patients during ongoing AMI.
Lead author, Dr. Borja Ibáñez, stated, “The association between neutrophil count and microvascular obstruction is abolished in metoprolol-treated AMI patients.” By inhibiting neutrophil-platelet interactions in AMI patients, metoprolol modifies neutrophil behavior and reduces injury on cardiac muscle.
Treatment to limit the irreversible damage caused by an MI is a critical area of research. Dr. Ibáñez concluded, “the priority after a heart attack remains the restoration of blood flow as soon as possible, but we need to prepare the heart for this by administering metoprolol.”
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