Protective Effect Of Pre-anticoagulation With Heparin In The Acute Lung Injury After Cardiopulmonary Resuscitation In Rabbites

Objectives To investigate the lung morphology injury following general ischemia–reperfusion caused by cardiac arrest and reversal the injury by pre–anticoagulation of heparin ,explore the protective effect of lung's ventilation function with pre–anticoagulation of heparin, to reveal the mechanism of the effect of the lung's ventilation function used heparin after cardiopulmonary resuscitation. Methods Using the modal of CPR after CA caused by apnoea in rabbites.The experimental animals were allocated randomly into 3 groups:shame group(group N,had 10 rabbites with anesthesia,operation but no apnoea) ,non–anticoagulation group (group NH,had 20 rabbites with anesthesia,operation and apnoea, i.v. the same dose saline to group H before apnoea ) , anticoagulation group (group H,had 12 rabbites with anesthesia,operation and apnoea, i.v. heparin 50 IU/100g before apnoea) . The animals of three groups were intraperitoneal injected with pentobarbital 30 mg/kg.After the anaesthetic affect was wonderful, nasal trachea cannula, fixed tube at 11.0-12.0 cm, femoral artery and femoral vein at right side were inserted with 22G needle.Then connect CO₂ probe to continuity monitor the PETCO₂, pin electrodes were pricked into limbs muscle to continuity monitor ECG..After lasting 10 min, i.v. vecuronium(1mg/kg), connected animal breathing machine, extubated until spontaneously breathing recovery. After 40 min of extubation, animals were killed with the method of bloodletting, inferior lobe of right lung was examined using light microscope.Beside the operation above, ten minutes after mechanical ventilation, the animals in group NH were clip the trachea cannula to result in cardiac arrest because of apnoea, and i.v. the same dose saline to group H before apnoea, CPR after clipping 13 minutes. The animals in group H were i.v. heparin 50 IU/100g before clipping the trachea cannula , CPR after clipping 13 minutes. Recorded all animals'weight, MBP,HR,PETCO₂,Pinhale,Pexhale of groupN,groupNH,groupH after 5 min of i.v. muscle relaxant and groupNH,groupH on moment of instantly ROSC,after 30 min of ROSC,after 60 min of ROSC. PT,APTT,TT,FIB were recorded before anesthesia in groupN and at the moment of ROSC instantly in groupNH,groupH; ABG (PH,PaO₂,PaCO₂,BE,SPO₂) was recorded before anesthesia and after 5 min of intubation in groupN,and also on moment of 5 min after i.v. muscle relaxant,1h after ROSC,0.5h after extubation groupNH,groupH. Recorded the time of apnoea～CA,CPR～ROSC,starting mechanical ventilation～extubation,VT and RR at 5 min after intubation and at the moment of stopping mechanical ventilation. Results There was no statistic significance of general condition among all animals (P>0.05).There was no change of ABG before and after intubation in groupN (P>0.05). There were 10 animals ROSC, 10 animals death in groupNH; There were 10 animals ROSC , 2 animals death in groupH. The animals which could not achieve ROSC shoud be discharged from the experiment. Contrast to groupNH, the death ratio decreased obviously in groupH(P<0.01).HR decreased obviously after 30 min of ROSC and after 60 min of ROSC in groupNH (P<0.01),MBP increased obviously at the moment of ROSC instantly (P<0.01), PETCO₂ increased obviously at the moment of ROSC instantly (P<0.01), increased after 30 min of ROSC (P<0.05), Pinhale,Pexhale increased obviously at the moment of ROSC instantly,after 30 min of ROSC,after 60 min of ROSC (P<0.01)。In groupNH, PH,BE decreased obviously 1h after ROSC,0.5h after extubation (P<0.01), PaO₂ decreased 1h after ROSC (P<0.05), PaO₂ decreased obviously 0.5h after extubation (P<0.01), PaCO₂ increased obviously 1h after ROSC (P<0.01), SPO₂ decreased 1h after ROSC and 0.5h extubation (P<0.05). In groupNH, VT decreased obviously when stopped mechanical ventilation,but RR increased obviously (P<0.05).In groupH, HR decreased obviously after 30 min of ROSC and after 60 min of ROSC (P<0.01),MBP increased at the moment of ROSC instantly (P<0.05), PETCO₂ increased at the moment of ROSC instantly (P<0.05), Pinhale,Pexhale increased obviously at the moment of ROSC instantly,after 30 min of ROSC,after 60 min of ROSC (P<0.01). In groupH, PH,BE decreased obviously 1h after ROSC,0.5h after spontaneously breathing recovery (P<0.01),PaO₂ decreased obviously 0.5h after extubation (P<0.01), SPO₂ decreased 0.5h after extubation (P<0.05). In groupH, VT decreased obviously when stopped mechanical ventilation (P<0.01),but RR increased obviously (P<0.01). Contrast to groupH, in groupNH VT decreased when stopped mechanical ventilation (P<0.05), HR decreased after 60 min of ROSC (P<0.05), PETCO₂ increased at the moment of ROSC instantly (P<0.05); PH,BE decreased obviously (P<0.01) , PaO₂ decreased (P<0.05) ,PETCO₂ increased obviously(P<0.01)at the moment of 1h after ROSC, PH decreased (P<0.05), PaO₂ decreased (P<0.05), BE decreased obviously after 0.5h of extubation(P<0.01). Contrast to groupH, the time of apnoea～CA decreased obviously (P<0.01),the time of CPR～ROSC increased obviously (P<0.01) in groupNH; contrast to groupN, PT,APTT decreased obviously (P<0.01),FIB increased obviously (P<0.01) in groupNH and groupH,contrast to groupNH, PT,APTT increased obviously (P<0.01),FIB decreased (P<0.05) in group H . Reviewed with light microscope, the lung histological changes in groupNH was the heaviest, the lung histological changes in groupH were lighter than that in groupNH.The scores of pathological manifestation groupNH were higher obviously than that in groupH (P<0.01). Conclution Using the modal of CPR after CA caused by apnoea in rabbites ,pre–anticoagulation with heparin can reverse the lung tissue injury including improving hypercoagulable and lessening the time of ischemia; pre–anticoagulation with heparin can improving lung's ventilation function.