Protective effects of PARP inhibition on liver microcirculation and function after haemorrhagic shock and resuscitation in male rats.
OBJECTIVE
The aim of this study was to investigate the impact of the water-soluble poly-(ADP)-ribose-polymerase (PARP) inhibitor 5-aminoisoquinolinone (5-AIQ) on liver microcirculation and function after haemorrhagic shock and resuscitation.


METHODS
Controlled, randomized animal study.


METHODS
University animal care facility and research laboratory.


METHODS
Male Sprague-Dawley rats were subjected to haemorrhagic shock for 1 h, followed by resuscitation with shed blood and crystalloid solution for a total of 5 h.


METHODS
The PARP inhibitor 5-AIQ (3 mg/kg; n=7) or vehicle (n=7) was administered 5 min prior to resuscitation. Sham-operated animals without induction of shock served as controls (n=7).


RESULTS
Using intravital fluorescence microscopy hepatic microcirculation was assessed at baseline, end of shock phase as well as 1 h and 5 h after resuscitation. Systemic arterial blood pressure and bile flow were continuously monitored. 5-AIQ treatment attenuated shock/resuscitation-induced increase of intrahepatic leukocyte-endothelial cell interaction with a marked reduction of both sinusoidal leukostasis and venular leukocyte adherence. Moreover, nutritive perfusion was found improved, guaranteeing sufficient oxygen supply to tissue, as indicated by low NADH autofluorescence, which was not different to that in controls. Most notably, excretory liver function reached baseline level over 5 h of reperfusion in 5-AIQ-treated animals.


CONCLUSIONS
In the present setting of shock/resuscitation in male rats the PARP inhibitor 5-AIQ proved to be very effective in ameliorating compromised liver microcirculation and function. Further research has to confirm that PARP inhibition is a suitable tool in the acute treatment of patients suffering from reduced circulating blood volume and thus microcirculatory organ dysfunction.
Roesner
J P
JP
University of Rostock, Department of Anaesthesiology and Intensive Care Medicine, 18055 Rostock, Germany.
Vagts
D A
DA
Iber
T
T
Eipel
C
C
Vollmar
B
B
Nöldge-Schomburg
G F E
GF
D000818:Animals; D007546:Isoquinolines / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D018709:Statistics, Nonparametric
C411425:5-aminoisoquinolinone; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors