Abstract 17405: Innate Immune Response Modulation Improves Outcomes After Acute Myocardial Infarction

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Abstract

Introduction: Myocardial infarction (MI) and resultant heart failure represent a major cause of morbidity and mortality. Improved interventions and therapies have increased rates of acute survival, leading to an increase in the incidence of ischemic cardiomyopathy and eventual heart failure. Following an MI, the acute inflammatory response may exacerbate the area of injury and diminish innate regenerative responses. In this study, proteomic analysis of thrombus aspirates from ST-elevation myocardial infarction (STEMI) patients identified an actionable target for immunomodulation, TNFα, predictive of improved outcomes and survival. The use of a TNFα inhibitor, Infliximab, was shown to shift the balance away from inflammation and towards regeneration in a porcine model of acute MI.

Hypothesis: Administration of Infliximab will result in a modulated inflammatory response leading to improved myocardial recovery following acute MI.

Methods: A porcine model of acute MI was generated via inflation of an angioplasty balloon catheter in the mid-LAD for 90 min. Infliximab was delivered systemically upon reperfusion. Hemodynamics and echocardiography were monitored throughout the infarct procedure, at 3 days and, 4-week follow-up. Tissue samples were collected 3 days post-MI for assessment of the immunologic response (n=7) and the remaining hearts were collected 4-weeks post-MI (n=9) and stained with Masson’s Trichrome to quantify scar size.

Results: Proteomic analysis of STEMI patient samples revealed a TNFα centric interaction network predictive of patient outcomes. In the porcine MI model, Infliximab therapy resulted in an anti-inflammatory response characterized by cellular phenotype and plasma proteomic analysis. Infliximab therapy showed significant improvement compared to untreated animals for left ventricular ejection fraction (53.8 ± 1.5 % vs. 33.0 ± 1.7 %, P<0.05) and scar size (8.31 ± 3.03 % vs. 17.41 ± 3.04 %, P<0.05). Plasma levels of IL-2, IL-4, IL-10, and, IL-12 were significantly altered at 3 days post-MI.

Conclusion: These results demonstrate that systemic Infliximab therapy post-STEMI diminished the acute inflammatory response resulting in preservation of contractility and prevention of adverse structural remodeling.

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