Mechanism of the protective effects of N-acetylcysteine on the heart of brain-dead Ba-Ma miniature pigs.
BACKGROUND
Severe stress response induced by brain death leads to a marked increase in the expression of inflammatory cytokines regulated by nuclear factor-kappaB (NF-kappaB). N-acetylcysteine may inhibit activation of the NF-kappaB pathway. This study examined the expression of NF-kappaB in the hearts of brain-dead Ba-Ma miniature pigs and the protection potential of N-acetylcysteine.


METHODS
Ba-Ma miniature pigs were randomized into 3 groups: control group (Group C), N-acetylcysteine-free group (Group B), and N-acetylcysteine treatment group (Group N). At 6, 12, and 24 hours after the initial brain death, serum cardiac troponin-T (cTnT), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 were examined. Heart tissue was taken 24 hours after the initial brain death. Structural changes of the heart and the expression of NF-kappaB were analyzed.


RESULTS
At 6 hours after the initial brain death, serum levels of cTnT, TNF-alpha, IL-1beta, and IL-6 in Groups B and N began to increase. Levels in Group B increased more dramatically than in Group N. At 24 hours, cardiocyte damage was documented, but the damage in Group N was less severe than that in Group B. The expression of NF-kappaB in Groups B and N increased, and expression in Group B increased more sharply than in Group N.


CONCLUSIONS
N-acetylcysteine can alleviate both structural and functional injury of the heart during brain death, which might be related to the inhibition of NF-kappaB expression and decreasing release of inflammatory mediators.
Zhai
Wenlong
W
Department of General Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, Peoples Republic of China.
Feng
Ruo
R
Huo
Liang
L
Li
Jie
J
Zhang
Shuijun
S
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001926:Brain Death / Q000473:pathology / Q000503:physiopathology; D017931:DNA Primers; D004195:Disease Models, Animal; D005215:Fasting; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007385:Intermittent Positive-Pressure Ventilation; D007442:Intubation, Intratracheal / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013552:Swine; D013556:Swine, Miniature; D020107:Troponin T / Q000097:blood / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D053583:Interleukin-1beta; D015850:Interleukin-6; D020107:Troponin T; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D000111:Acetylcysteine