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.