Experimental Investigation Of Protective Effects By Exogenous Low Dose Carbon Monoxide Inhalation On The Donor Lung Of Rats

1. Establishment of the isolated lung transplantation and reperfusion model in rats.Objectives:To establish a simple,reliable and economical lung transplantation model in rats for the study of improving the function of donor lung.Methods:The donor lung blocks were harvested and flushed with the low-potassium-dextran(LPD) solution through the main pulmonary artery and stored at 4℃for 12 hours.The donor lung was connected to the recipient rat with conduit and pump.During circulation,the venous blood from the right superior vena cava of the donor rat was perfused through the pulmonary artery into the donor lung by means of a double-head roller pump.The donor rat lung was ventilated with an O₂ fraction of 100% at a tidal volume of 5.0 ml/rat and a rate of 50 breaths/min.Reperfusion was performed at 37℃for 60 minutes. PvO2,PvCO2,Hb,PH,PaO2,PaCO2 were obtained by blood gas analysis of the blood inflow to and out flow from the donor lung at 20 mininute intervals and mean pulmonary artery pressure(mPAP) and peak airway pressure(PawP) were measured at the same time.Results:The ricipient rat can transpose arterial blood into venous blood well with small fluctuate of PvO2,PvCO2,Hb,PH(P＞0.05).The donor lung can maintain good oxygenation and compliance in the early phase of reperfusion.But with the time passed by,the reperfusion injury was observed according to the lower lung function and compliance with the decreasing PaO2,the increasing PaCO2, mPAP and PawP (P＜0.05或P＜0.01 ) .Conclusions: The isolated rat lung transplantation and reperfusion model can imitate the donor lung perfusion and it was simple,reliable,and economical.The model can be used for the study of improving the function of the donor lung.2. Experimental investigation of protective effects by exogenous low dose carbon monoxide inhalation on the donor lung of rats.Objectives:Successful lung transplantation has been limited by the high incidence of primary graft failure(PGF). There is mounting evidence that the stress response gene heine oxygenase-1 (HO-1) and/or its catalytic byproduct carbon monoxide (CO)confers protection against tissue and cellular injury.We investigate the protection effects of exogenous low dose carbon monoxide inhalation on donor lung of rat after long time,cold isehemic preservation.Methods:Twenty-four rats were randomly divided into two groups(A , B).All lungs were flushed with low-potassium-dextran(LPD) solution,harvested in block,stored inflated at 4℃for 12 hours,and reperfused for 1 hour. In group A(n=6),donor lungs were stored,and reperfused.In group B(n=6),donor lungs were treated with low dose carbon monoxide inhalation during the whole transplantation proeedure.PaO2,PaP, PawP were measured at every 20minutes intervals during reperfusion.After reperfusion,the wet-to-dry(W/D) ratio,MDA,myeloperoxidase(MPO) activity, interlukin-8(IL-8),apoptosis index and ultrastructure of lung tissue were obtained.Results:The decreased PaO2 and increased mPAP, PawP were observed with the reperfusion time passed by in both groups.However, the degree of decreased PaO2 and increased mPAP, PawP in groupB were lighter than those in group A (P＜0.05或P＜0.01 ) .After reperfusion,the W/T, MDA,MPO,IL-8 and Apoptosis Index were respectively lower in group B than in group A.Histological .and apoptosis evaluation revealed less injury in group B than group A.Conclusions: Exogenous low dose carbon monoxide inhalation on donor lung of rat can effectively attenuate lung isehemic/reperfusion injury associated with its properties of antioxidative,anti-inflamatory and antiapoptotic effects.