Carvedilol administration in acute myocardial infarction results in stronger inhibition of early markers of left ventricular remodeling than metoprolol.
BACKGROUND
The structural secuelae of acute myocardial infarction (AMI) is mostly dictated by left ventricular (LV) remodelling, leading to heart failure. Monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a critical role in LV remodelling. β-blockers are first line therapy for AMI and heart failure; however, the mechanisms responsible for their benefits remain poorly understood. Different β-blocker agents have been shown to exert beneficial activities both in AMI and heart failure, however, their role in early remodelling after ischemia/reperfusion is to be fully elucidated. We sought to compare the effect of 2 of the most prescribed β-blocker agents in early markers of LV remodelling after AMI.


METHODS
A reperfused AMI was induced in Yorshire pigs, being randomized to early intravenous carvedilol, metoprolol or placebo. Twenty-four hours after reperfusion markers of early remodelling were addressed in the LV.


RESULTS
The early administration of both β-blockers is able to significantly reduce macrophage infiltration as well as the expression and activity of MCP-1 and MMP-2 compared to placebo. The effects of carvedilol were much stronger than those of metoprolol. Conversely, carvedilol upregulated the expression TIMP-2 to a greater extent than metoprolol.


CONCLUSIONS
In an AMI model closely mimicking human pathophysiology, the early administration of carvedilol reduced the expression of markers associated with early LV remodelling to greater extent than metoprolol. These findings may explain the superior clinical benefits exerted by carvedilol in heart failure.
Cimmino
Giovanni
G
Atherothrombosis Research Unit, Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Ibanez
Borja
B
Giannarelli
Chiara
C
Prat-González
Susanna
S
Hutter
Randolph
R
Garcia
Mario
M
Sanz
Javier
J
Fuster
Valentin
V
Badimon
Juan J
JJ
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D015536:Down-Regulation / Q000187:drug effects*; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D013552:Swine; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D015415:Biomarkers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol