Early cytotoxic lymphocyte localization to the brain following resuscitation in a porcine model of asphyxial cardiac arrest: A pilot study

Abstract

Introduction: Out-of-hospital cardiac arrest (OHCA) is a major cause of morbidity and mortality in the US. Of major concern is a lack of therapies to mitigate associated brain injury. Immune cell infiltration (ICI) into the brain, which may exacerbate injury post-resuscitation, is one possible therapeutic target, although the post-OHCA immune response has not been fully characterized. Objective: In this pilot study, we aimed to detect early post-resuscitation cytotoxic lymphocyte ICI in porcine brain using a model of opioid-mediated asphyxial OHCA. Methods: Ten young, healthy swine (26.7+/-3.4 kg) were sedated, anaesthetized and paralyzed. In eight of the animals, this was followed by induction of asphyxial OHCA via fentanyl bolus and concurrent airway occlusion. The remaining two ‘sham’ animals were instrumented but did not undergo asphyxia. After nine minutes of asphyxia, mechanical CPR and manual ventilations were started, in an initial BLS followed by ALS configuration. At termination of resuscitation or euthanasia, the whole brain was removed. Immune cells were extracted and analyzed via flow cytometry. Results: 304 +/− 62.2 cells/g were discovered to be CD8 single positive cells in animals that achieved ROSC, 481 +/− 274.4 cells/g in animals that did not achieve ROSC, and 40 +/− 11.31 cells/g in sham animals. CD8 single positive cells made up 0.473 +/− 0.24% of detected cells in animals that achieved ROSC, 0.395 +/− 0.062% in animals that did not achieve ROSC, and 0.19 +/− 0.014% in sham animals (No ROSC vs Sham, p = 0.012). Conclusions: These data suggest that cytotoxic lymphocytes may be localizing to the brain during cardiac arrest resuscitation.

Keywords

• Post cardiac arrest syndrome
• Cardiac arrest
• Resuscitation
• Lymphocyte
• Cytotoxic
• T-lymphocyte