Effect of the combination of fibrin glue and growth hormone on intestinal anastomoses in a pig model of traumatic shock associated with peritonitis.
BACKGROUND
Intra-abdominal sepsis and hemorrhagic shock have been found to impair the healing of intestinal anastomoses. The present study examined whether fibrin glue (FG) and recombinant human growth hormone (GH) can improve intestinal primary anastomotic healing in a pig model of traumatic shock associated with peritonitis. Further, the study was designed to investigate the probable mechanism of these agents.


METHODS
Female anesthetized pigs were divided into five groups. Group sham (n = 7), pigs without traumatic shock had small bowel resection anastomoses; group control (n = 14), pigs had bowel resection anastomoses 24 h after abdominal gunshot plus exsanguination/resuscitation; group FG (n = 14); group GH (n = 14); group FG/GH (n = 14), pigs received FG, recombinant GH, or both, respectively. Recombinant GH was given daily for 7 days. Blood samples were collected daily for measurement of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha levels. Investigations also included adhesion formation, anastomotic bursting pressure, tensile strength, hydroxyproline (HP) content, myeloperoxidase (MPO), tumor necrosis factor (NF)-kappaB activity, and histology analysis 10 days later. A second experiment (n = 20 subjects assigned to each of the five groups) was designed to study survival during the first 20 postoperative days.


RESULTS
Traumatic shock associated with peritonitis led to significant decreases in intestinal anastomotic bursting pressures, tensile strengths, and tissue hydroxyproline content, along with severe adhesion formation, increases in MPO activity and NF-kappaB activity, and plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Both FG and recombinant GH treatment led to early significant increases in plasma levels of TNF-alpha and IL-6. At the same time, FG alone, unlike recombinant GH alone, led to significant increases in anastomotic bursting pressures, tensile strength, and tissue HP content, along with decreases in anastomotic MPO and NF-kappaB activity and later plasma levels of TNF-a and IL-6. The FG group also developed more marked neoangiogenesis and collagen deposition on histology analysis. However, FG and recombinant GH synergistically effected improved anastomotic healing, abolishing the infaust effects promoted by recombinant GH. Adhesion formation after intestinal anastomosis could not be lowered by FG alone or by the combination of FG and recombinant GH. Both FG alone and FG/GH, in contrast to GH alone and control treatment, significantly prolonged the survival time of experimental animals.


CONCLUSIONS
We found that FG, but not recombinant GH, could lower the risk of anastomotic leakage, improve intestinal anastomotic healing, and prolong survival in a pig model of traumatic shock associated with peritonitis. Both FG and recombinant GH synergistically effected improved intestinal anastomotic healing. It was suggested that GH could be used locally to promote intestinal anastomotic healing in intra-abdominal peritonitis.
Wang
Pengfei
P
Medical College, Nanjing University, Nanjing, Jiangsu Province 210002, People's Republic of China.
Wang
Jian
J
Zhang
Wenbo
W
Li
Yousheng
Y
Li
Jieshou
J
D000714:Anastomosis, Surgical / Q000379:methods; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology*; D013006:Growth Hormone / Q000627:therapeutic use*; D007082:Ileum / Q000473:pathology / Q000601:surgery; D015850:Interleukin-6 / Q000097:blood; D007583:Jejunum / Q000473:pathology / Q000601:surgery; D008233:Lymphotoxin-alpha / Q000097:blood; D010538:Peritonitis / Q000150:complications / Q000401:mortality / Q000601:surgery; D009195:Peroxidase / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012774:Shock, Traumatic / Q000150:complications / Q000401:mortality / Q000601:surgery*; D013529:Surgical Wound Dehiscence / Q000517:prevention & control; D013552:Swine; D014014:Tissue Adhesives / Q000494:pharmacology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D014948:Wounds, Gunshot / Q000150:complications / Q000401:mortality / Q000601:surgery*
D015718:Fibrin Tissue Adhesive; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014014:Tissue Adhesives; D014409:Tumor Necrosis Factor-alpha; D013006:Growth Hormone; D009195:Peroxidase