Changes in interleukin-10 mRNA expression are predictive for 9-day survival of pigs in an emergency preservation and resuscitation model.
OBJECTIVE
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, 31-38 kg) were subjected to 15 min of ventricular fibrillation, followed by intra-arrest cardiopulmonary bypass cooling for 1, 3, or 5 min achieving brain temperatures (Tbr) of 30.4+/-1.6, 24.2+/-4.6 and 18.8+/-4.0 degrees C. After 40 min of controlled rewarming, pigs were defibrillated and kept at Tbr of 34.5 degrees C for 20 h, survival was for 9 days. Plasma samples were analysed for interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), 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-alpha, interferon-gamma, inducible NO synthase, and heme oxygenase-1 gene expressions.


RESULTS
Plasma IL-6 and TNF-alpha 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).


CONCLUSIONS
The systemic inflammatory response syndrome after cardiac arrest was reflected by a remarkable increase of plasma IL-6 and TNF-alpha 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.
Sipos
Wolfgang
W
Clinical Department for Farm Animals, University of Veterinary Medicine Vienna, Austria.
Duvigneau
Catharina
C
Sterz
Fritz
F
Weihs
Wolfgang
W
Krizanac
Danica
D
Bayegan
Keywan
K
Graf
Alexandra
A
Hartl
Romana
R
Janata
Andreas
A
Holzer
Michael
M
Behringer
Wilhelm
W
D000818:Animals; D015415:Biomarkers; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D015536:Down-Regulation; D004554:Electric Countershock; D005260:Female; D006323:Heart Arrest / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D007036:Hypothermia, Induced; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D012333:RNA, Messenger; D012151:Resuscitation; D015996:Survival Rate; D034421:Sus scrofa; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D014693:Ventricular Fibrillation / Q000209:etiology
D015415:Biomarkers; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10