Whereas prior experiments in juvenile pigs had reported infarct size reduction by intravenous metoprolol early during myocardial ischaemia, two major clinical trials in patients with reperfused acute myocardial infarction were equivocal. We, therefore, went back and tested the translational robustness of infarct size reduction by metoprolol in minipigs. Using a power analysis-based prospective design, we pretreated 20 anaesthetised adult Göttingen minipigs with 1 mg kg⁻¹ metoprolol or placebo and subjected them to 60-min coronary occlusion and 180-min reperfusion. Primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was a secondary endpoint. There was no significant reduction in infarct size (46 ± 8% of area at risk with metoprolol vs. 42 ± 8% with placebo) or area of no-reflow (19 ± 21% of infarct size with metoprolol vs. 15 ± 23% with placebo). However, the inverse relationship between infarct size and ischaemic regional myocardial blood flow was modestly, but significantly shifted downwards with metoprolol, whereas ischaemic blood flow tended to be reduced by metoprolol. With an additional dose of 1 mg kg⁻¹ metoprolol after 30-min ischaemia in 4 additional pigs, infarct size was also not reduced (54 ± 9% vs. 46 ± 8% in 3 contemporary placebo, n.s.), and area of no-reflow tended to be increased (59 ± 20% vs. 29 ± 12%, n.s.).

Infarct size reduction by metoprolol in pigs is not robust, and this result reflects the equivocal clinical trials. The lack of infarct size reduction may be the result of opposite effects of reduced infarct size at any given blood flow and reduced blood flow, possibly through unopposed alpha-adrenergic coronary vasoconstriction.

虽然之前在幼猪中进行的实验报道了心肌缺血早期静脉注射美托洛尔可减少梗塞面积，但针对再灌注急性心肌梗塞患者的两项主要临床试验结果却模棱两可。因此，我们回过头来测试了美托洛尔在小型猪中减少梗塞面积的转化稳健性。使用基于功效分析的前瞻性设计，我们用 1 mg kg ^-1美托洛尔或安慰剂对 20 只麻醉的成年哥廷根小型猪进行预处理，并对它们进行 60 分钟的冠状动脉闭塞和 180 分钟的再灌注。主要终点是梗死面积（氯化三苯基四唑染色）占危险区域的比例；无回流区（硫黄素-S 染色）是次要终点。梗塞面积（美托洛尔组梗塞面积为 46 ± 8%，安慰剂组为 42 ± 8%）或无复流面积（美托洛尔组梗塞面积为 19 ± 21%，安慰剂组为 15 ± 23%）没有显着减少。与安慰剂）。然而，梗死面积与缺血区域心肌血流量之间的负相关关系不大，但美托洛尔组显着向下移动，而美托洛尔则倾向于减少缺血血流量。在另外 4 头猪缺血 30 分钟后，追加剂量 1 mg kg ^-1美托洛尔，梗死面积也没有减少（3 个当代安慰剂中为 54 ± 9%，ns 为 46 ± 8%），并且梗塞面积没有减少。 -回流焊趋于增加（59 ± 20% vs. 29 ± 12%，ns）。

美托洛尔对猪梗塞面积的减少作用并不明显，这一结果反映了临床试验的模棱两可。梗塞面积没有减少可能是在任何给定血流量下梗塞面积减少和血流量减少（可能通过不受对抗的α-肾上腺素能冠状血管收缩）产生相反作用的结果。