Changes in interleukin-10 mRNA expression are predictive for 9-day survival of pigs in an emergency preservation and resuscitation model☆

Abstract 

Aim of the study

This study aimed at evaluating (I) the impact of different intra-arrest hypothermia levels on the expression of selected cytokines and (II) their prognostic value for 9-day survival.

Methods

Female Large White pigs (n=21, 31–38kg) were subjected to 15min of ventricular fibrillation, followed by intra-arrest cardiopulmonary bypass cooling for 1, 3, or 5min achieving brain temperatures (Tbr) of 30.4±1.6, 24.2±4.6 and 18.8±4.0°C. After 40min of controlled rewarming, pigs were defibrillated and kept at Tbr of 34.5°C for 20h, survival was for 9 days. Plasma samples were analysed for interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 levels by ELISA. Total RNA out of peripheral blood mononuclear cells was analysed by real-time PCR for IL-1, IL-2, IL-4, IL-10, TNF-α, interferon-γ, inducible NO synthase, and heme oxygenase-1 gene expressions.

Results

Plasma IL-6 and TNF-α levels significantly (p=0.0001 and 0.0003) increased in all animals within 1h after resuscitation with no significant differences between groups. Pigs surviving exhibited a decrease in IL-10 expression between baseline and intra-arrest values as compared to non-surviving animals, which showed a slight increase (p=0.0078). ROC curve analysis revealed that changes in IL-10 expression had a good prognostic power for survival to day 9 (area under the curve=0.882).

Conclusion

The systemic inflammatory response syndrome after cardiac arrest was reflected by a remarkable increase of plasma IL-6 and TNF-α levels. Intra-arrest hypothermia levels did not influence the expression of selected cytokines. As prognostic marker for survival IL-10 was identified with decreasing mRNA levels during cardiac arrest in survivors.

Keywords: Cardiopulmonary resuscitation (CPR), Heart arrest, Hypothermia, Inflammatory response, Outcome, Temperature