The Effects Of Rapid Hypothermia Early After Resuscitation On Intestinal Mucous Injury After Cardiopulmonary Resuscitation In Swine

Objective:To rapidly induce therapeutic hypothermia(TH)early after resuscitation,and then investigate its protective effects on post-resuscitation intestinal mucous injury and potential mechanisms in a porcine model of cardiopulmonary resuscitation(CPR).Methods:Forty-one healthy male domestic swine weighing 36±2 kg were randomly divided into 5 groups using a random number table:sham group(S group,n=5),normothermia group(NT group,n=9),surface cooling group(SC group,n=9),EC group(n=9)and CRRT group(n=9).The sham animals experienced general preparation only.In the other groups,the procedure including an 8 min of electrically induced ventricular fibrillation and then 5 min of CPR was used to establish the pig model of cardiac arrest and resuscitation.At 5 min post-resuscitation,TH was induced in the SC,EC and CRRT groups to reach a targeted temperature of 33?,and then this temperature was maintained until 24 h post-resuscitation,and finally the animals were rewarmed at a rate of 1 ?/h to achieve the normal temperature.During the induction and maintenance phases,the cooling in the SC and EC groups was implemented by a cooling blanket and an EC catheter,respectively.In the meanwhile,the cooling in the CRRT group was implemented by cooling the blood in the extracorporeal circuit until 8 h post-resuscitation,and followed by SC to maintain TH until 24 h post-resuscitation.During the rewarming phase,all the animals were rewarmed by the surface blanket.In the S and NT groups,normal temperature was continuously maintained by the surface blanket.The efficacy of cardiopulmonary resuscitation and its resuscitation outcomes were recorded.After resuscitation,core temperature was continuously monitored for 30 h in all animals.At 1 h,3 h,6 h,12 h,24 h and 30 h after resuscitation,blood samples were collected via femoral vein to measure the contents of intestinal fatty acid binding protein(IFABP)and the activities of diamine oxidase(DAO)in serum.At 30 h after resuscitation,all the resuscitated animals were euthanized,and then the tissue of distal ileum was rapidly harvested to measure intestinal inflammatory cytokines such as tumor necrosis factor-alpha(TNF-a)and interleukin-6(IL-6)contents,oxidative stress-related indicators malondialdehyde(MDA)contents and superoxide dismutase(SOD)activities,and the index of apoptotic cells and also its marker protein caspase-3 expression.Results:1.There were no differences in body weight and baseline hemodynamics,blood gas,lactate,core temperature among the five groups(all P>0.05).During CPR,no differences in the levels of coronary perfusion pressure,rate of resuscitation success,duration of CPR,number of defibrillations and dosage of epinephrine were observed among the NT,SC,EC and CRRT groups.(all P>0.05).2.During the induction of TH,the rates of decrease of core temperature in the SC,EC and CRRT groups were 1.5±0.4 ?/h,2.8±0.7 ?/h and 9.8±1.6 ?/h,respectively.Additionally,the time to target temperature in the three groups were 185±35 min,102±17 min and 28±7 min,respectively.Consequently,the efficacy of cooling in the EC and CRRT groups were significantly greater than that in the SC group(both P<0.05).During the maintenance and rewarming phases,no difference in core temperature was observed among the three groups(all P>0.05).3.Intestinal mucous injury was observed in animals after successful resuscitation,which was indicated by the changes in serum IFABP contents and DAO activities.We observed that serum IFABP contents and DAO activities after resuscitation were gradually increased and then decreased,in which their peak values were reached at 24 h and 12 h,respectively.However,when compared with the NT group,the contents of IFABP starting 12 h after resuscitation and the activities of DAO starting 6 h after resuscitation were significantly decreased in the SC group,and the contents of IFABP starting 6 h after resuscitation and the activities of DAO starting 3 h after resuscitation were significantly reduced in the EC and CRRT groups(all P<0.05).In addition,the contents of IFABP starting 24 h after resuscitation were further significantly decreased and the activities of DAO starting 12 h after resuscitation were further significantly reduced in the EC and CRRT groups compared to the SC group(all P<0.05).4.After resuscitation,the inflammatory response,oxidative stress and cell apoptosis were observed in intestinal tissue in animals.However,the contents of TNF-a,IL-6 and MDA were significantly decreased while the activities of DAO were significantly increased in intestinal tissue in all hypothermic animals when compared with the NT group(all P<0.05).Similarly,the index of apoptotic cells was significantly decreased and the expression of caspase-3 was significantly reduced in the three hypothermic groups compared to the NT group(all P<0.05).Additionally,those pathological injuries mentioned above were further significantly milder in the EC and CRRT groups than in the SC group(both P<0.05).Conclusion:Rapidly induced hypothermia early after porcine CPR could improve intestinal mucous injury,in which the potential mechanisms were related to the alleviation of tissue inflammation,oxidative stress and cell apoptosis.Additionally,the protective effects were significantly greater when rapid hypothermia was induced via EC catheter or CRRT compared to conventional SC.