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AIM To investigate the hepatic microcirculatory changes due to Haemoxygenase(HO),effect of HO inhibition on remote ischemic preconditioning(RIPC) and modulation of CINC.METHODS Eight groups of animals were studied- Sham,ischemia reperfusion injury(IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion,RIPC(remote ischemic preconditioning) + IRI group,remote ischemic preconditioning in sham(RIPC + Sham),PDTC + IR(Pyridodithiocarbamate,HO donor),Zn PP + RIPC + IRI(Zinc protoporphyrin prior to preconditioning),IR-24(45 min of ischemia followed by 24 h of reperfusion),RIPC+IR-24(preconditioning prior to. After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS Velocity of flow(160.83 ± 12.24 μm/s),sinusoidal flow(8.42 ± 1.19) and sinusoidal perfusion index(42.12 ± 7.28) in hepatic IR were lower(P < 0.05) in comparison to RIPC and PDTC(HO inducer). RIPC increased velocity of flow(328.04 ± 19.13 μm/s),sinusoidal flow(17.75 ± 2.59) and the sinusoidal perfusion index(67.28 ± 1.82)(P < 0.05). PDTC(HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity(300.88 ± 22.109 μm/s),sinusoidal flow(17.66 ± 3.71) and sinusoidal perfusion(82.33 ± 3.5) to near sham levels. Zn PP(HO inhibition) reduced velocity of flow of RBC in the RIPC group(170.74 ± 13.43 μm/s and sinusoidal flow in the RIPC group(9.46 ± 1.34). Zn PP in RIPC(60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules(769.05 ± 87.48) and sinusoids(97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules(219.66 ± 93.79) and sinusoids(25.69 ± 9.08)(P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules(89.58 ± 58.32) and sinusoids(17.98 ± 11.01)(P < 0.05) reproducing the effects of RIPC. Zn PP(HO inhibition) increased venular(589.04 ± 144.36) and sinusoidal neutrophil adhesion in preconditioned animals(121.39 ± 30.65)(P < 0.05). IR after 24 h of reperfusion increased venular and sinusoidal neutrophil adhesion in comparison to the early phase and was significantly reduced by RIPC. Hepatocellular cell death in IRI(80.83 ± 13.03),RIPC + IR(17.35 ± 2.47),and PTDC+IR(11.66 ± 1.17) Zn PP + RIPC + IR(41.33 ± 3.07) reduced hepatocellular death. Zn PP significantly increased hepatocellular death(P < 0.05 PTDC/RIPC vs Zn PP and IR). The CINC cytokine levels in sham(101.32 ± 6.42). RIPC + sham(412.18 ± 65.24) as compared to sham(P < 0.05). Hepatic IR(644.08 ± 181.24)(P < 0.05). RIPC CINC-1 levels in the early phase(401.62 ± 78.56). And PDTC(HO inducer) CINC-1 levels in hepatic IR(413.36 ± 63.06) were significantly lower. HO inhibition in preconditioned animals with Zinc protoporphyrin increased serum CINC levels(521.81 ± 74.9)(P < 0.05). The serum CINC levels were high in the late phase of hepatic IR(15306 ± 1222.04). RIPC reduced CINC levels in the late phase of IR(467.46 ± 26.06),P < 0.05.CONCLUSION RIPC protects hepatic microcirculation by induction of HO and modulation of CINC in hepatic IR.
AIM To investigate the hepatic microcirculatory changes due to Haemoxygenase (HO), effect of HO inhibition on remote ischemic preconditioning (RIPC) and modulation of CINC. METHODS Eight groups of animals were studied- Sham, ischemia reperfusion injury (IRI) the animals were to 45 min of hepatic ischemia followed by three hours of reperfusion, RIPC (remote ischemic preconditioning) + IRI group, remote ischemic preconditioning in sham (RIPC + Sham), PDTC + IR (Pyridodithiocarbamate, HO donor) Zinc protoporphyrin prior to preconditioning, 45 min of ischemia followed by 24 h of reperfusion, RIPC + IR-24 after 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were RESULTS Velocity of flow (160.83 ± 12.24 μm / s), sinusoidal flow (8.42 ± 1.19) and sinusoidal perfusion index (42.12 ± 7.28) in hepatic IR were lower (P <0.05) in comparison to RIPC and PDTC ) RIPC increased velocity of flow (328.04 ± 19. PDTC (HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity (300.88 ± s), sinusoidal flow (17.75 ± 2.59) and the sinusoidal perfusion index (67.28 ± 1.82) (PPV), reduced sinusoidal flow (17.66 ± 3.71) and sinusoidal perfusion (82.33 ± 3.5) to near sham levels. Zn PP (HO inhibition) reduced velocity of flow of RBC in the RIPC group (170.74 ± 13.43 μm / s and The sinusoidal flow in the RIPC group (9.46 ± 1.34). Zn PP in RIPC (60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury was seen in both posts inusoidal venules (769.05 ± 87.48) and Neutrophil adhesion in RIPC + IR injury was reduced in both postsignal venules (219.66 ± 93.79) and sinusoids (25.69 ± 9.08) (P <0.05). PDTC reduced neutrophil adhesion in both postsignal venules (89.58 ± 58.32 ) and sinusoids (17.98 ± 11.01) (P <0.05) reproducing the effects of RIPC. Zn PP (HO inhibition) increased venular (589.04 144.36) and sinusoidaIR after 24 h of reperfusion increased venular and sinusoidal neutrophil adhesion in comparison to the early phase and was significantly reduced by RIPC. Hepatocellular cell death in IRI (80.83 ± (P <0.05 PTDC / RIPC vs IR (17.35 ± 2.47), and PTDC + IR (11.66 ± 1.17) Zn PP + RIPC + IR (41.33 ± 3.07) reduced hepatocellular death. ZnCp and IR). The CINC cytokine levels in sham (101.32 ± 6.42). RIPC + sham (412.18 ± 65.24) as compared to sham (P <0.05). Hepatic IR (644.08 ± 181.24) HO inhibition in preconditioned animals with Zinc protoporphyrin increased serum CINC levels (521.81), CINC-1 levels in the early phase (401.62 ± 78.56). And PDTC ± 74.9) (P <0.05). The serum CINC levels were high in the late phase of hepatic IR (15306 ± 1222.04). RIPC reduced CINC Levels in the late phase of IR (467.46 ± 26.06), P <0.05. CONCLUSION RIPC protects hepatic microcirculation by induction of HO and modulation of CINC in hepatic IR.