Abstract 1324: Anakinra, Recombinant Human Interleukin-1 Receptor Antagonist, Inhibits Apoptosis In Acute Myocardial Infarction
Background. Recent data suggest that Interleukin-1 receptor antagonist (IL-1Ra) may be cardioprotective during ischemia. The aim of the current study was to test the impact of exogenous recombinant human IL-1Ra (anakinra) in experimental acute myocardial infarction (AMI).
Methods. Two animal studies were conducted:
immediate anakinra administration during ischemia in the mouse and
delayed anakinra administration 24 hours after ischemia in the rat.
Thirty-two ICR mice and 16 Wistar rats underwent surgical coronary artery ligation. Anakinra 1 mg/Kg intraperitoneal was given during surgery (mouse) or on day 2 (rat) and then daily for 6 doses in half of the animals. Animals underwent transthoracic echocardiography (TTE) before surgery and 7 days later just prior to sacrifice. A blood sample was taken to detect circulating IL-1beta in 8 rats. Histological analysis was performed to evaluate cardiomyocyte apoptosis in the peri-infarct regions. The anti-apoptotic effect of anakinra was tested in primary rat cardiomyocyte culture. The effect of anakinra on caspase-1 activity was tested in vitro.
Results. At 7 days, 9 of the 10 mice and 4 of the 4 rats treated with anakinra were alive (93%) vs 7 of the 14 mice and 5 of the 8 rats treated with saline (54%, P=0.027). No differences in infarct size at 24 hours were observed. Anakinra significantly reduced apoptosis in both the immediate and delayed treatment groups (3.1±0.2 vs 0.5±0.3%, P<0.001, and 4.2±0.4 vs 1.1±0.2%, P<0.001; respectively). When compared with saline-treated animals, anakinra-treated animals showed signs of significantly better ventricular remodelling (P<0.05 for EDD, ESD, and FS). We found no difference in IL-1beta between the 2 groups. Anakinra (0.025 ng/ml) significantly inhibited ischemia-induced apoptosis by approximately 40% in a primary rat culture (P<0.001) and anakinra (100 nM) also significantly inhibited caspase-1 activity by approximately 50% (P<0.001)
Conclusions. Immediate or delayed administration of anakinra during AMI significantly ameliorates the remodeling process by inhibition of cardiomyocyte apoptosis in an experimental model of AMI. This may have strong clinical implications for the prevention of post-ischemic cardiac remodeling and heart failure.