Cardioprotection by early metoprolol- attenuation of ischemic vs. reperfusion injury?
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Cardioprotection by early metoprolol‑ attenuation of ischemic vs. reperfusion injury? Petra Kleinbongard1 Received: 20 July 2020 / Accepted: 20 July 2020 © The Author(s) 2020
There is still a need for adjunct cardioprotection on top of timely reperfusion since mortality and morbidity, notably from heart failure, in patients with acute myocardial infarction remain high [11, 12]. There are plenty preclinical studies reporting mechanical and/or pharmacological strategies to reduce myocardial ischemia/reperfusion injury [6, 17]. However, the translation from preclinical and clinical proof-of-concept studies into better clinical outcome for patients with acute myocardial infarction has been disappointing so far [9, 13]. Among the pharmacological strategies, the beta-blocker metoprolol when given after 15 min of a total of 90 min coronary occlusion reduced infarct size and improved left ventricular functional recovery in pigs [15]. Also, in a proof-of-concept study in patients with acute ST segment elevation myocardial infarction (The Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial) metoprolol when given as early as possible i.e. in the ambulance -, reduced infarct size [14]. However, the subsequent phase III trial (the Early Intravenous Beta-Blockers in Patients With STSegment Elevation Myocardial Infarction Before Primary Percutaneous Coronary Intervention (EARLY-BAMI) trial) did not confirm the prior study and was neutral for infarct size and left ventricular function [20]. 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].
This comment refers to the article available at https://doi. org/10.1007/s00395-020-0812-4. * Petra Kleinbongard petra.kleinbongard@uk‑essen.de 1
Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, Hufelandstr. 55, 45122 Essen, Germany
In a closed-chest anesthetized pig model the distal left anterior descending coronary artery was occluded with an intracoronary balloon for varying durations from 20 to 60 min with subsequent reperfusion. Intravenous metoprolol (0.75 mg/kg) was given at 20 min coronary occlusion. Effects on ventricular fibrillation, infarct size, coronary microvascular obstruction and left ventricular function (by magnetic resonance imaging) were assessed at days 7 and 45. Metoprolol reduced ventricular fibrillation and improved survival. Metoprolol had no effect on infarct size with coronary occlusion of short duration (20 and 25 min). On the other extreme, with 60 min coronary occlusion, infarct size occupied almost the entire area at risk (determined by contrast multidetector computed tomography), and metoprolol also had no effect. However, in the time window from 30 to 50 min coronary occlusion, metoprolol significantly reduced infarct size. This
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