Carvedilol administration in acute myocardial infarction results in stronger inhibition of early markers of left ventricular remodeling than metoprolol

Giovanni Cimmino, Borja Ibanez, Chiara Giannarelli, Susanna Prat-González, Randolph Hutter, Mario J. Garcia, Javier Sanz, Valentin Fuster, Juan J. Badimon

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)256-261
Number of pages6
JournalInternational Journal of Cardiology
Volume153
Issue number3
DOIs
StatePublished - Dec 15 2011
Externally publishedYes

Fingerprint

Ventricular Remodeling
Metoprolol
Heart Failure
Myocardial Infarction
Chemokine CCL2
Reperfusion
Placebos
Tissue Inhibitor of Metalloproteinase-2
Matrix Metalloproteinase 2
Matrix Metalloproteinases
carvedilol
Swine
Ischemia
Macrophages

Keywords

  • Adrenergic receptors
  • Heart failure
  • Ischemia/reperfusion
  • Myocardial infarction
  • Remodelling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Carvedilol administration in acute myocardial infarction results in stronger inhibition of early markers of left ventricular remodeling than metoprolol. / Cimmino, Giovanni; Ibanez, Borja; Giannarelli, Chiara; Prat-González, Susanna; Hutter, Randolph; Garcia, Mario J.; Sanz, Javier; Fuster, Valentin; Badimon, Juan J.

In: International Journal of Cardiology, Vol. 153, No. 3, 15.12.2011, p. 256-261.

Research output: Contribution to journalArticle

Cimmino, Giovanni ; Ibanez, Borja ; Giannarelli, Chiara ; Prat-González, Susanna ; Hutter, Randolph ; Garcia, Mario J. ; Sanz, Javier ; Fuster, Valentin ; Badimon, Juan J. / Carvedilol administration in acute myocardial infarction results in stronger inhibition of early markers of left ventricular remodeling than metoprolol. In: International Journal of Cardiology. 2011 ; Vol. 153, No. 3. pp. 256-261.
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AU - Ibanez, Borja

AU - Giannarelli, Chiara

AU - Prat-González, Susanna

AU - Hutter, Randolph

AU - Garcia, Mario J.

AU - Sanz, Javier

AU - Fuster, Valentin

AU - Badimon, Juan J.

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AB - 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.

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