Metoprolol blunts the time-dependent progression of infarct size

Abstract

Early metoprolol administration protects against myocardial ischemia–reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.

Cardioprotection by early metoprolol- attenuation of ischemic vs. reperfusion injury?

“…In retrospect, it turned out that the dose of metoprolol was lower and the start of treatment later in EARLY-BAMI than METOCARD-CNIC [5]. The importance of early treatment was now systematically addressed in an experimental study by Ibanez and collaborators [19].…”

Veno-occlusive unloading of the heart reduces infarct size in experimental ischemia–reperfusion

“…The relative importance of applying unloading during ischemia or after reperfusion was not systematically investigated. We anticipate that delaying the start of unloading will attenuate its impact on infarct size, because we expect that the cardioprotective effect of veno-occlusive unloading occurs primarily during ischemia and very early reperfusion, similar to remote ischemic conditioning 26 and intravenous metoprolol 27 . There have been conflicting results regarding the timing of mechanical unloading relative to timing of reperfusion.…”

BTK Promotes Atherosclerosis by Regulating Oxidative Stress, Mitochondrial Injury, and ER Stress of Macrophages

“…Macrophages were cultured in 96-well plates and incubated for 30 minutes with MitoTracker Red. Then, the macrophages were counterstained with DAPI for 10 min and visualized by fluorescence microscopy (LSM 710, Carl Zeiss) [ 42 , 43 ].…”