Recombinant human interleukin-1 receptor antagonist provides cardioprotection during myocardial ischemia reperfusion in the mouse.

PURPOSE: Acute myocardial infarction (AMI) drives an intense inflammatory response that contributes to infarct healing and cardiac remodeling. Recently, different studies have identified a role of interleukin-1 (IL-1) in the development of adverse cardiac remodeling. However, in animal models of AMI IL-1 has been shown to be cardioprotective in preconditioning, raising the question of clinical safety of therapeutic IL-1 blockade for autoinflammatory diseases or for the prevention or the treatment of AMI. In this study we proposed to evaluate the effects of pretreatment with recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) on ischemia reperfusion (I/R) injury to the heart. METHODS: RhIL-1Ra was given 4 h or 30 min before the surgical induction of I/R. Left ventricular ejection fraction(LVEF) and infarct size were assessed to determine the effects of the drug pretreatment compared to vehicle treated mice. RESULTS: RhIL-1Ra, given 4 h or 30 min before the onset of the ischemia, showed marked cardioprotection though preservation of the LVEF (no change vs sham operated mice) and the reduction of the infarct size (-40 % vs vehicle-treated mice). No differences were observed between the two groups of rhIL-1Ra treatment. CONCLUSIONS: IL-1 blockade therapies using rhIL-1Ra prior the onset of AMI protects the myocardium and preserves cardiac function.

Thoracic Sympathectomy for Severe Refractory Multivessel Coronary Artery Spasm.

Coronary artery spasm is a rare but potentially fatal disease. Herein, we report a case of recurrent ST-segment myocardial infarctions and ventricular fibrillation complicating severe multivessel coronary artery spasm successfully treated with bilateral thoracic surgical sympathectomy.

Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study).

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome of exercise intolerance due to impaired myocardial relaxation and/or increased stiffness. Patients with HFpEF often show signs of chronic systemic inflammation, and experimental studies have shown that interleukin-1 (IL-1), a key proinflammatory cytokine, impairs myocardial relaxation. The aim of the present study was to determine the effects of IL-1 blockade with anakinra on aerobic exercise capacity in patients with HFpEF and plasma C-reactive protein (CRP) >2 mg/L (reflecting increased IL-1 activity). A total of 12 patients were enrolled in a double-blind, randomized, placebo-controlled, crossover trial and assigned 1:1 to receive 1 of the 2 treatments (anakinra 100 mg or placebo) for 14 days and an additional 14 days of the alternate treatment (placebo or anakinra). The cardiopulmonary exercise test was performed at baseline, after the first 14 days, and after the second 14 days of treatment. The placebo-corrected interval change in peak oxygen consumption was chosen as the primary end point. All 12 patients enrolled in the present study and receiving treatment completed both phases and experienced no major adverse events. Anakinra led to a statistically significant improvement in peak oxygen consumption (+1.2 ml/kg/min, p = 0.009) and a significant reduction in plasma CRP levels (-74%, p = 0.006). The reduction in CRP levels correlated with the improvement in peak oxygen consumption (R = -0.60, p = 0.002). Three patients (25%) had mild and self-limiting injection site reactions. In conclusion, IL-1 blockade with anakinra for 14 days significantly reduced the systemic inflammatory response and improved the aerobic exercise capacity of patients with HFpEF and elevated plasma CRP levels.