Objective To evaluate the role of haeme oxygenase-1 (HO-1) in remote limb ischemic preconditioning (RLIP)-induced attenuation of lung ischemia-reperfusion (I/R) injury in rabbits.Methods Twenty-four Japanese White Rabbits,aged 4-5 months,weighing 2.0-2.5 kg,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (S group),I/R group,RLIP group and zinc protoporphyrin (ZnPP,an inhibitor of HO-1) plus RLIP group (ZnPP + RLIP group).Lung I/R was produced by 60 min occlusion of the left lung hilum followed by 180 min of reperfusion in I/R,RLIP and ZnPP + RLIP groups.RLIP and ZnPP + RLIP groups received 3 cycles of 10 min ischemia followed by 10 min reperfusion in the bilateral hind limbs immediately before occlusion of the left lung hilum.In ZnPP + RLIP group,ZnPP 10 μmol/kg was injected intravenously 10 min prior to hind limb ischemia and the rest of the procedures were similar to those previously described in RLIP group.At the end of reperfusion,arterial blood samples were collected for blood gas analysis.The animals were then sacrificed and pulmonary specimens were obtained for microscopic examination of the pathological changes which were scored (lung injury score,LIS) and for determination of wet/dry lung weight ratio (W/D ratio),myleoperoxidase (MPO) activity,malondialdehyde (MDA) content and expression and activity of HO-1 in the lung tissues.Results Compared with group S,PaO2 was significantly decreased,and LIS,W/D ratio,MPO activity,MDA content,and HO-1 expression and activity were increased in I/R group (P < 0.01).Compared with I/R group,PaO2 and HO-1 expression and activity were significantly increased,and LIS,W/D ratio,MPO activity and MDA content were decreased in RLIP group (P < 0.01).Compared with RLIP group,PaO2 and HO-1 expression and activity were significantly decreased,and LIS,W/D ratio,MPO activity and MDA content were increased in ZnPP + RLIP group (P < 0.01).Conclusion RLIP up-regulates HO-1 expression and enhances HO-1 activity,thus reducing lung I/R injury in rabbits.
OBJECTIVE To investigate the effect of fluid resuscitation on oxygenation of subjects with hemorrhagic shock in early period of first visit to area of high altitude, an experiment in dogs was performed. METHODS A model of serious hemorrhagic shock was reproduced by exsanguination resulting in a lowering of mean arterial pressure to (35+/-5) mm Hg (1 mm Hg=0.133 kPa) maintain for 1 hour. Thirteen mongrel dogs were carried to an area of 3,780 metres above sea level from an area of 1,510 metres, and they were randomly divided into three groups, namely lactated Ringer's (LR) group, 6% hydroxyethyl starch (HES) group, and control group. The dogs in LR group were infused intravenously LR in 1.5 times the volume of blood loss; those in 6% HES group were given HES in equal volume. No fluid infusion was given in the control group. After 1 hour of resuscitation, LR was intravenously given at 5 ml.kg(-1).h(-1) in all groups as maintenance dose. The changes in oxygenation were observed. RESULTS All animals in control group were dead after 2 hours. One hour after establishment of shock, the oxygen consumption (VO(2)), oxygen delivery (DO(2)), oxygen extraction ratio (O(2)ER), arterial oxygen saturation (SaO(2)) in two resuscitation groups were significantly lower than those before shock, but venous oxygen saturation (Sv(2)) and alveolar-arterial oxygen difference (A-aDO(2)) were significantly higher (all P<0.05). In LR group, the oxygenation parameters including VO(2), DO(2), O(2)ER, SaO(2) after 2 hours of resuscitation were significantly higher than those 1 hour after shock, while A-aDO(2) was significantly lower (all P<0.05); and in HES group, VO(2), DO(2), O(2)ER were significantly higher than those 1 hour after shock, while SvO(2) was significantly lower (all P<0.05). CONCLUSION All dogs with serious hemorrhagic shock would die of hemorrhagic shock in the early period of entering a high altitude area if fluid resuscitation is denied. Two hours after infusion of LR in 1.5 times of quantity of blood loss, oxygenation can be restored to expected normal values. Infusion of 6% HES with an equal volume of blood loss, oxygenation dose not reach expected level 2 hours after resuscitation.
Objective To investigate the effect of fluid resuscitation on hemodynamics in dogs with hemorrhagic shock at the initial stage of getting high altitude. Method he models of severe hemohagic shock were established in 13 mongrel dogs after they were brought to the high altitude a/ea and were mndondvvided inIo 3 group: LR group(n=3),6% HES group(n=5)and control group(n=5).The dogs in LR group wefe intravenously infused with lactated Ringers solution in 1.5 limes exsanguinated volume;those in 6% HES group were given hydroxyethyl starch in equal volume of exsanquination. A drop of solution waft noven to dogs in con,trol group.One hour after restritation,lactated Ringers solution waft infused at 5 Ilps as maintenance dose.The hemodynmnic variables were recorded.Results All animals in control group died two hour later.In LR group,the hemedynamie variables including MAP,CO,PAWP,CVP,LVSWI and RVSWI two hours after infiion were signifieantly higher than those.one hour after infusion(P<0.05),while HR,SVRd PVR were significantly lower(P<0.05).In dogs of 6% HES group,CO,PAP,PAWP,CVP,SVR and PVR two hours after infusion were significantly higher than those one hour after infusion(P<0.05),but MAP.HR.CI,LVSWI and RVSWI were not significantly different(P>0.05).Conclusions All of three doith hen rhagic shock would die(3/3)at the initial stage of being brought to high altitude alles without fluid resuscitation. Fluid resuscitation with LR solution 1.5 times the exsanquinated volume was effective and safe. The infusion of 6% hydroxyethyl starch at equal volume of exsanqination may easily cause heart failure or pulmonary edema.
Objective: To investigate the effects of rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ (PPARγ), on acute lung inflammation in endotoxemic rats. Methods: Twenty-four male Wistar rats were randomly divided into four groups (n = 6): control group, rosiglitazone (ROSI, 0.3 mg/kg i.v.) group, endotoxin (LPS, 6 mg/kg i.v.) group and ROSI (0.3 mg/kg i.v.) + LPS (6 mg/kg i.v.) group. Four hours after LPS or saline injection, myeloperoxidase (MPO) activity, tumor necrosis factors (TNF-α) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) concentrations, and nuclear factor κB (NF-κB) activation were measured in lung tissues. Results: Compared with the LPS group, MPO activity, TNF-α and CINC-1 concentrations, and NF-κB activity in the lung tissues were significantly attenuated in the ROSI + LPS group (P < 0.01). Conclusion: Rosiglitazone could reduce pulmonary inflammation caused by endotoxemia. The anti-inflammatory effect of rosiglitazone may be connected with the inhibition of NF-κB activation.