TY - JOUR
T1 - The cardioprotection granted by metoprolol is restricted to its administration prior to coronary reperfusion
AU - Ibanez, Borja
AU - Cimmino, Giovanni
AU - Prat-González, Susanna
AU - Vilahur, Gemma
AU - Hutter, Randolph
AU - García, Mario J.
AU - Fuster, Valentin
AU - Sanz, Javier
AU - Badimon, Lina
AU - Badimon, Juan J.
N1 - Funding Information:
BI was granted by the Working Group on Ischemic Heart Disease of the Spanish Society of Cardiology , SP by a Fellowship of Fundación CajaMadrid , and GV is a Juan de la Cierva investigator of MEC. GV and LB are members of CIBEROBN-Institute Carlos III and are funded by PNS 2006-10091 from MEC, Spain .
PY - 2011/3/17
Y1 - 2011/3/17
N2 - Background: Myocardial infarct size is a strong predictor of cardiovascular events. Intravenous metoprolol before coronary reperfusion has been shown to reduce infarct size; however, it is unknown whether oral metoprolol initiated early after reperfusion, as clinical guidelines recommend, is similarly cardioprotective. We compared the extent of myocardial salvage associated with intravenous pre-reperfusion-metoprolol administration in comparison with oral post-reperfusion-metoprolol or placebo. We also studied the effect on suspected markers of reperfusion injury. Methods: Thirty Yorkshire-pigs underwent a reperfused myocardial infarction, being randomized to pre-reperfusion- metoprolol, post-reperfusion-metoprolol or placebo. Cardiac magnetic resonance imaging was performed in eighteen pigs at day 3 for the quantification of salvaged myocardium. The amounts of at-risk and infarcted myocardium were quantified using T2-weighted and post-contrast delayed enhancement imaging, respectively. Twelve animals were sacrificed after 24 h for reperfusion injury analysis. Results: The pre-reperfusion-metoprolol group had significantly larger salvaged myocardium than the post-reperfusion-metoprolol or the placebo groups (31 ± 4%, 13 ± 6%, and 7 ± 3% of myocardium at-risk respectively). Post-mortem analyses suggest lesser myocardial reperfusion injury in the pre-reperfusion-metoprolol in comparison with the other 2 groups (lower neutrophil infiltration, decreased myocardial apoptosis, and higher activation of the salvage-kinase phospho-Akt). Salvaged myocardium and reperfusion injury pair wise comparisons proved there were significant differences between the pre-reperfusion-metoprolol and the other 2 groups, but not among the latter two. Conclusions: The intravenous administration of metoprolol before coronary reperfusion results in larger myocardial salvage than its oral administration initiated early after reperfusion. If confirmed in the clinical setting, the timing and route of β-blocker initiation could be revisited.
AB - Background: Myocardial infarct size is a strong predictor of cardiovascular events. Intravenous metoprolol before coronary reperfusion has been shown to reduce infarct size; however, it is unknown whether oral metoprolol initiated early after reperfusion, as clinical guidelines recommend, is similarly cardioprotective. We compared the extent of myocardial salvage associated with intravenous pre-reperfusion-metoprolol administration in comparison with oral post-reperfusion-metoprolol or placebo. We also studied the effect on suspected markers of reperfusion injury. Methods: Thirty Yorkshire-pigs underwent a reperfused myocardial infarction, being randomized to pre-reperfusion- metoprolol, post-reperfusion-metoprolol or placebo. Cardiac magnetic resonance imaging was performed in eighteen pigs at day 3 for the quantification of salvaged myocardium. The amounts of at-risk and infarcted myocardium were quantified using T2-weighted and post-contrast delayed enhancement imaging, respectively. Twelve animals were sacrificed after 24 h for reperfusion injury analysis. Results: The pre-reperfusion-metoprolol group had significantly larger salvaged myocardium than the post-reperfusion-metoprolol or the placebo groups (31 ± 4%, 13 ± 6%, and 7 ± 3% of myocardium at-risk respectively). Post-mortem analyses suggest lesser myocardial reperfusion injury in the pre-reperfusion-metoprolol in comparison with the other 2 groups (lower neutrophil infiltration, decreased myocardial apoptosis, and higher activation of the salvage-kinase phospho-Akt). Salvaged myocardium and reperfusion injury pair wise comparisons proved there were significant differences between the pre-reperfusion-metoprolol and the other 2 groups, but not among the latter two. Conclusions: The intravenous administration of metoprolol before coronary reperfusion results in larger myocardial salvage than its oral administration initiated early after reperfusion. If confirmed in the clinical setting, the timing and route of β-blocker initiation could be revisited.
KW - Beta-blockers
KW - Cardioprotection
KW - MRI
KW - Myocardial infarction
KW - Myocardial salvage
KW - Reperfusion injury
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U2 - 10.1016/j.ijcard.2009.09.551
DO - 10.1016/j.ijcard.2009.09.551
M3 - Article
C2 - 19913314
AN - SCOPUS:79952484817
SN - 0167-5273
VL - 147
SP - 428
EP - 432
JO - International Journal of Cardiology
JF - International Journal of Cardiology
IS - 3
ER -