Anakinra in experimental acute myocardial infarction--does dosage or duration of treatment matter?
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Salloum
Fadi N
FN
VCU Pauley Heart Center, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA 23298-0281, USA.
Chau
Vinh
V
Varma
Amit
A
Hoke
Nicholas N
NN
Toldo
Stefano
S
Biondi-Zoccai
Giuseppe G L
GG
Crea
Filippo
F
Vetrovec
George W
GW
Abbate
Antonio
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009203:Myocardial Infarction / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects
D002316:Cardiotonic Agents; D053590:Interleukin 1 Receptor Antagonist Protein