Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC230
Leucocyte infiltration in experimental warm hepatic ischemia reperfusion model; effect of ischemic pre and post conditioning strategies and implications of adhesion molecules
Z. A. Alrefaie1, L. Rashed2
1. Physiology department, Faculty of Medicine, Cairo University, Cairo, Egypt. 2. Biochemistry department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Aim: Few studies are available regarding the role of ischemic postconditioning (IPO) in the prevention of hepatic Ischemia-reperfusion (I/R) injury. The present study wonders if IPO can attenuate leucocyte infiltration in I/R model. We also aimed to compare such effect of IPO with that produced by ischemic preconditioning (IPC) and to study their relation to vascular cell adhesion molecule-1 (VCAM-1) and E selectin adhesion molecules. Methods: 40 male Wistar rats (anesthetized by intraperitoneal injection of pentobarbital 40 mg/Kg body weight) were randomly divided into 4 groups (n=10); group I (control group, subjected to sham laparotomy). Group II (I/R, subjected to ischemia of the left lateral and median lobes using atraumatic clamp for 60 minutes to induce partial hepatic warm ischemia followed by removal of the clamp and reperfusion for 120 minutes). Group III (IPC, exposed to 10 minutes ischemia and 15 minutes reperfusion prior to I/R); and Group IV (IPO, underwent 3 brief cycles of ischemia separated by reperfusion with 30 seconds each at the onset of reperfusion following the 60 minutes ischemia). The study protocol was approved by the ethical committee, Kasr-Al Aini Faculty of Medicine, Cairo University. Colorimetric assessment of serum ALT and albumin as indicators of hepatocellular injury was carried out. VCAM-1 and E selectin levels were determined in serum and ischemic liver tissue homogenate using ELISA. The myeloperoxidase (MPO) activity which is used as an index of leucocyte accumulation was assayed spectrophotometrically. Statistical analysis was made using one way analysis of variance; data are presented as mean ± standard deviation and association of variables was calculated using Pearson correlation (SPSS version 12). P values < 0.05 were considered as statistically significant Results: IPO attenuated the liver functional damage following I/R by reducing serum ALT (P < 0.05), and increasing albumin level which didn’t reach significance. IPO also decreased liver MPO (P < 0.01 compared to I/R group), although this reduction was less marked when compared with IPC group (P < 0.001). IPO significantly lowered the elevation in liver VCAM-1 and E selectins produced by I/R (P < 0.01 for both). Correlation results demonstrated a positive correlation between liver VCAM-1 and MPO (r = 0.723, P < 0.05) and a negative correlation between soluble fraction of E selectin and MPO (r = -0.687, P < 0.05) in the I/R group. Conclusion Our results revealed that IPO could contribute to liver protection against I/R injury by attenuating leucocyte infiltration and decreasing VCAM-1 and E selectin levels in the liver. We also postulate that soluble E selectin can be used as a serum marker to anticipate the degree of leucocyte infiltration in hepatic I/R injury.
Where applicable, experiments conform with Society ethical requirements