The Protective Effects Of Different Cooling Techniques On Kidney Injury After Porcine Cardiopulmonary Resuscitation And Its Mechanisms

Objective:To induce rapid hypothermia by either an esophageal cooling device or continuous renal replacement therapy(CRRT)at the early stage after resuscitation,and then investigate their protective effects on post-resuscitation kidney injury and the potential mechanisms.Methods:Forty-one male domestic pigs weighing 36±2 kg were utilized.The animals were randomly divided into 5 groups:sham operation group(S group,n=5),normothermia group(NT group,n=9),surface cooling group(SC group,n=9),esophageal cooling group(EC group,n=9),and CRRT cooling group(CRRT-C group,n=9).The animals in the S group only experienced the surgical operation without the procedure of cardiac arrest and resuscitation.The pig model was established by 8 mins of untreated ventricular fibrillation and then 5 mins of CPR in the other four groups.At 5 min after successful resuscitation,therapeutic hypothermia was induced by either an esophageal cooling device in the EC group or a surface cooling blanket in the SC group to reach a targeted temperature of 33 0C until 24 hrs after resuscitation,and then followed by a rewarming rate of 1?/h for 5 hrs.At the meanwhile,therapeutic hypothermia was induced by CRRT to reach a targeted temperature of 33? until 8 hrs after resuscitation,and then maintained by a cooling blanket until 24 hrs after resuscitation followed by a same rewarming rate in the CRRT-C group.A normal temperature of 38.0±0.5? was maintained by a cooling blanket throughout the experiment in the S and NT groups.The temperature was continuously monitored during 30 hrs post-resuscitation.At 1 h,3 h,6 h,12 h,24 h and 30 h post-resuscitation,the concentrations of creatinine(Cr)and blood urea nitrogen(BUN)in serum were measured.At 30 h post-resuscitation,the pigs were sacrificed,and then renal tissue was rapidly obtained for the determination of tumor necrosis factor-alpha(TNF-a)and interleukin-6(IL-6)contents by enzyme linked immunosorbent assay,malondialdehyde(MDA)content by thiobarbituric acid method,superoxide dismutase(SOD)activity by xanthine oxidase method,cell apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,and caspase-3 expression by imunohistochemistry.Results:1.After resuscitation,the average rate of temperature decrease was respectively 9.8?/h in the CRRT-C group,2.8?/h in the EC group,and 1.5?/h in the SC group;the time to target temperature was respectively 28 mins in the CRRT-C group,102 mins in the EC group,and 185 mins in the SC group.The efficacy of cooling was significantly improved in the CRRT-C and EC groups when compared with the SC group(all P<0.05).2.Compared with the S group,post-resuscitation renal dysfunction was observed in the other four groups,which was indicated by increased concentrations of serum Cr and BUN.Compared with the NT group,the concentrations of serum Cr after 3 hrs post-resuscitation and the concentrations of serum BUN after 6 hrs post-resuscitation were all significantly decreased in the SC,EC and CRRT-C groups(all P<0.05).Compared with the SC group,the concentrations of Cr and BUN in serum after 6 hrs post-resuscitation in the CRRT-C group and after 12 hrs post-resuscitation in the EC group were all further significantly decreased(all P<0.05).3.Compared with the S group,the inflammatory response,oxidative stress and cell apoptosis were all observed in renal tissue in the other four groups,which were indicated by the increase in TNF-?,IL-6 and MDA contents,cell apoptosis index and caspase-3 expression,and the decrease in SOD activity.Compared with the NT group,the contents of TNF-a,IL-6 and MDA were significantly decreased,cell apoptosis index and caspase-3 expression were significantly reduced,and SOD activity was markedly increased in renal tissue in the SC,EC and CRRT-C groups.Compared with the SC group,the inflammatory response,oxidative stress and cell apoptosis in renal tissue were further significantly alleviated in the EC and CRRT-C groups.Conclusion:In a porcine model of CPR,rapid hypothermia could be successfully induced by an esophageal cooling device or CRRT,and consequently produced a greater protective effects for post-resuscitation kidney injury when compared to the conventional surface cooling.The protective mechanisms are related to the inhibition of inflammation,oxidative stress and cell apoptosis.