Journal
CARDIOVASCULAR DRUGS AND THERAPY
Volume 23, Issue 2, Pages 129-135Publisher
SPRINGER
DOI: 10.1007/s10557-008-6154-3
Keywords
Interleukin-1; Cytokine; Apoptosis; Remodelling; Myocardial infarction; Anakinra
Funding
- Thomas F. Jeffress and Kate Miller Jeffress Trust award
- Societa Italiana di Cardiologia
- American Heart Association
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Interleukin-1 (IL-1) receptor antagonist (Ra) is a naturally occurring IL-1 blocker with a cardioprotective effect during acute myocardial infarction (AMI). Anakinra, recombinant-human IL-1Ra, has been used to prevent heart failure in a mouse model of AMI. The aim of this study was to determine the optimal therapeutic regimen for anakinra in AMI. We performed dose-response experiments comparing anakinra 1 mg/kg with 100 mg/kg doses, and duration-response experiments comparing 1-week to 2-week treatment. Echocardiography was used to assess cardiac remodeling and systolic function. Histopathology was used to detect apoptotic cardiomyocytes. A higher dose of anakinra was not associated with additional improvement in cardiac remodeling or function. The 2-week anakinra treatment had sustained and more favorable remodeling and systolic function compared to 1-week treatment with significantly smaller left ventricular end-systolic diameter and greater fractional shortening 4 weeks after AMI. Anakinra inhibits apoptosis and ameliorates cardiac remodeling up to 4 weeks after infarction. A 2-week regimen is superior to a 1-week regimen, whereas a higher dose did not provide any further benefit over standard doses.
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