Abstract P2043: Interleukin-1 Blockade Restores Exercise Capacity After Non-reperfused Acute Myocardial Infarction In The Mouse.

Abstract

Background: Acute myocardial infarction (AMI) is associated with an intense inflammatory response promoting progression to heart failure (HF), characterized by dyspnea, fatigue, exercise intolerance. Interleukin-1 (IL-1) is the prototypical inflammatory cytokine increased in AMI. IL-1 injections reduce exercise capacity in healthy mice. Whether IL-1 reduces exercise capacity after AMI is unknown. Hypothesis: IL-1 blockade preserves exercise capacity in mice with experimental AMI. Methods: Ten-week-old male CD1 mice (N=45) were trained to run on a treadmill. Baseline exercise capacity was assessed. Based on the distance run, the mice were divided into tertiles. Mice in the middle tertile underwent surgical ligation of the coronary artery. Ten mice survived and were randomly assigned to treatment with daily intraperitoneal injections with anakinra, a recombinant human IL-1 receptor antagonist (10 mg/kg, 0.2 ml, N=4), or 0.9% NaCl vehicle (N=6). We measured exercise capacity at 1, 2, and 4 weeks. Data were analyzed using T-test for unpaired groups and are presented as mean and standard error of mean. Results: Baseline exercise capacity was 217±16 and 230±16 m in the anakinra and vehicle groups, respectively. Exercise capacity was significantly reduced 1 week after surgery in both groups (-57±9% vs -60±7%, P=0.80; P<0.01 vs respective baseline). By week 4, however, anakinra treatment significantly improved exercise capacity compared to the vehicle (+42±4% vs +8±7%, P<0.001) (Figure). Conclusion: Non-reperfused AMI leads to a severe reduction in exercise capacity that is reversed by IL-1 blockade. These data support IL-1 as a therapeutic target for preventing HF after AMI.