Fingolimod Reduces Cardiac Macrophage Infiltration after Experimental Subarachnoid Hemorrhage (P13-7.002)

Abstract

<h3>Objective:</h3> We investigated macrophage infiltration into the rat heart after experimental subarachnoid hemorrhage (SAH) and whether this is attenuated by treatment with the immunomodulatory agent fingolimod. <h3>Background:</h3> Upwards of 70% of aneurysmal SAH patients suffer from cardiac dysfunction despite not having any primary cardiac disease. It is unclear if this is related to systemic inflammation or autonomic dysregulation. Previously, our lab showed that early elevations in serum white blood cells can predict cardiac injury in SAH patients. <h3>Design/Methods:</h3> SAH was induced in rats using the endovascular perforation model and compared to sham controls (n=4 per group). Additional sham and SAH animals were treated with fingolimod, given intraperitoneally 3 hours after the procedure (0.5 mg/kg, single dose). Cardiac tissue was harvested two days postoperatively and stained for the macrophage marker Iba-1 at both the apex and base of the heart. Blinded analysis was performed to Iba-1+ cell count, area, size, and circularity. Significance was determined by one-way ANOVA with Tukey’s multiple comparisons test. <h3>Results:</h3> The number of Iba-1+ cells was lower in the sham and SAH-fingolimod treated groups than in the SAH-vehicle group (SAH-vehicle: 40.87±2.43 cells/hpf; sham: 11.8±0.71 cells/hpf, p&lt;0.0001; SAH-fingolimod 7.8±0.37 cells/hpf, p&lt;0.0001). There was no difference in average Iba-1+ cell size across groups (p&gt;0.05). Attenuation in the number of Iba-1⁺ cells in the heart was observed at both the apex and base; however, the effect of fingolimod was more pronounced at the apex. Additionally, Iba-1⁺ cells at the apex displayed increased circularity compared to shams (p=0.0232), which may be associated with a more amoeboid, activated state. <h3>Conclusions:</h3> Following SAH, there are increased macrophages in the heart compared to shams, indicating increased cardiac inflammation. Treatment with fingolimod reduces macrophage infiltration and may lead to improved outcomes. Additional studies are needed to investigate if immunomodulation reduces SAH-associated cardiac dysfunction. <b>Disclosure:</b> Mr. Geraghty has received publishing royalties from a publication relating to health care. Mr. Saini has nothing to disclose. Dr. Testai has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Swanson Martin &amp; Bell, LLP. Dr. Testai has received publishing royalties from a publication relating to health care.