Intraabdominal bacterial infections significantly alter regeneration and function of the liver in a rat model of major hepatectomy.
BACKGROUND
No systematic investigations of interactions of postoperative infections and liver regeneration after resection are available.


METHODS
Male Sprague-Dawley rats underwent sham operation, 70% partial hepatectomy (PH), cecal ligation and puncture (CLP), or synchronous PH + CLP and were killed at regular intervals. Liver regeneration and function were measured by the mitotic index, Bromo-deoxy-uridine labeling, and Ki-67 as well as bilirubin, albumin, and indocyanine green plasma disappearance rate. The inflammatory response was evaluated by determination of IL-1beta and myeloperoxidase (MPO) activity. Bacterial concentrations in different organs were quantified.


RESULTS
Simultaneous CLP + PH resulted in a significantly delayed regeneration kinetic, which was most pronounced at 24 h. This was preceded by hyperinflammation with increased liberation of pro-inflammatory cytokines in the PH + CLP group at 6 h. After 48 h, the pro-inflammatory response declined, and regeneration proceeded also in the PH + CLP group. Liver function was found impaired in both groups; however, it was significantly worse in the PH + CLP group. Especially after 48 h, when regeneration peaked in this group, liver function significantly declined. At 96 h, only minor differences were seen, but the persistently elevated proliferative activity indicated the delay of regeneration after PH + CLP.


CONCLUSIONS
The present analysis shows that infectious conditions delay liver regeneration. Our data suggest a cross-linkage of both conditions via the functional liver capacity. A direct role of microorganisms seems unlikely; however, the inhibitory effect of the pro-inflammatory cytokines may be involved.
Seehofer
Daniel
D
Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany. daniel.seehofer@charite.de
Stockmann
Martin
M
Schirmeier
Anja
A
Nüssler
Andreas K
AK
Cho
Si-Young Ria
SY
Rayes
Nada
N
Koch
Martin
M
Schiller
Reinhold
R
Menger
Michael D
MD
Neuhaus
Peter
P
D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism / Q000503:physiopathology*; D015415:Biomarkers / Q000032:analysis; D002432:Cecum / Q000293:injuries; D006498:Hepatectomy / Q000009:adverse effects / Q000379:methods; D053583:Interleukin-1beta / Q000032:analysis*; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008940:Mitotic Index; D023421:Models, Animal; D009195:Peroxidase / Q000032:analysis*; D011677:Punctures; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015415:Biomarkers; C508585:IL1B protein, human; D053583:Interleukin-1beta; D009195:Peroxidase