Metoprolol blunts the time-dependent progression of infarct size.

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.

Nutritional preconditioning by marine omega-3 fatty acids in patients with ST-segment elevation myocardial infarction: A METOCARD-CNIC trial substudy.

BACKGROUND: Marine omega-3 eicosapentaenoic acid (EPA) is readily incorporated into cardiomyocyte membranes, partially displacing the omega-6 arachidonic acid (AA). Whereas AA is a substrate for pro-inflammatory eicosanoids, the release of EPA from cell membranes generates anti-inflammatory lipid mediators, contributing to the infarct-limiting effect observed experimental models. Clinical data are lacking. METHODS: In this observational study conducted in 100 patients with a reperfused anterior ST-elevation myocardial infarction (STEMI), at hospital admission we quantified by gas-chromatography the red blood cell proportions of AA, EPA, and the AA:EPA ratio, a valid surrogate for cardiomyocyte membrane content. Patients underwent cardiac magnetic resonance imaging in the acute phase (one week post-STEMI), and at long-term (6 months) follow-up. Infarct size (delayed gadolinium enhancement) and cardiac function (left ventricular ejection fraction [LVEF]) were correlated with exposures of interest by multivariate regression analysis. RESULTS: AA:EPA ratio directly related to acute infarct size (coefficient [95% CI]: 6.19 [1.68 to 10.69], P = 0.008) and inversely to long-term LVEF (coefficient [95% CI]: − 4.02 [− 7.15 to − 0.89], P = 0.012). EPA inversely related to acute infarct size (coefficient [95% CI]: − 6.58; [− 11.46 to − 1.70]; P = 0.009), while a direct association with LVEF at follow-up (coefficient [95% CI]: 3.67 [0.25 to 7.08]; P = 0.036) was observed. CONCLUSIONS: A low AA:EPA ratio in red blood cells at the time of STEMI is associated with smaller acute infarct size and preserved long-term ventricular function. Our results are consistent with prior work in experimental models and add to the notion of omega-3 fatty acids as a healthy fat. TRIAL REGISTRATION: http://www.clinicaltrials.gov/NCT01311700