DOI: 10.1161/circ.148.suppl_1.169 ISSN: 0009-7322

Abstract 169: Effect of Fingolimod-Induced Leucocyte Sequestration on Inflammatory Response and Neurological Damages in a Porcine Model of Cardiac Arrest

Yara Abi Zeid Daou, Antoine Bois, Naoto Watanabe, Estelle Faucher, Fanny Lidouren, Mathieu Surenaud, Sophie Hue, Matthias Kohlhauer, Bijan Ghaleh, Renaud Tissier
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Introduction: Early alterations in immune function are observed after cardiac arrest, with sepsis-like syndrome and cerebral infiltration by leucocytes.

Hypothesis: The pharmacological sequestration of leucocytes within lymphoid tissues with the sphingosine 1-phosphate analog fingolimod could mitigate the inflammatory response and provide neuroprotection after cardiac arrest.

Methods: Anesthetized pigs underwent 14 min of ventricular fibrillation followed by resuscitation. Animals randomly received fingolimod (1 mg/kg i.v.) or saline two hours prior to cardiac arrest (n=6 in each group). Blood samples were collected for blood cells count and dosages of cytokines (Luminex) and neurofilament light chain (NFL, Quantmetrix). Neurological dysfunction was assessed 24 hours after cardiac arrest.

Results: In the Fingolimod group, total blood leucocytes and lymphocytes counts were reduced as compared to Controls, both prior to and after cardiac arrest (Figure 1A). Conversely, blood levels of Interleukin [IL]-R1a, IL-6, IL-8, IL-18 were not different among groups (e.g., Figure 1B for IL-1Ra). As illustrated in Figures 1C and 1D, NFL blood levels and neurological dysfunction score were also not different in both groups after cardiac arrest.

Conclusion: Despite reducing blood total leucocytes and lymphocytes count, fingolimod did mitigate neither the circulating levels of pro- or anti-inflammatory cytokines nor the neurological damage following cardiac arrest. Leucocytes sequestration in lymphocyte tissue might not be sufficient to provide neuroprotection after cardiac arrest.

Figure 1: Blood lymphocytes (A), Interleukin-1Ra blood level (B), Neurofilament light chain blood level (NFL; C) and Neurological Dysfunction score at Day 1 after cardiac arrest

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