| Objective:To investigate the effects of Shenfu injection(SFI)on multiple organ injry and the potential mechanisms after traumatic cardiac arrest(TCA).Methods:Twenty-one male domestic white swine weighing 33.1±3.6 kg were divided into three groups randomly:Sham group(n=5),TCA group(n=9)and SFI group(n=7).The animals in the Sham group only experienced tracheal intubation and surgical operation without the process of blood loss and cardiopulmonary resuscitation(CPR).In TCA and SFI groups,after 40%estimated blood volume removed within 20 min,the animals were subjected to 5 min of untreated ventricular fibrillation and 5 min of CPR,Simultaneously,crystal liquid of 60%estimated blood volume was infused in one hour,and followed by reinfusion of 50%the lost blood in another one hour.SFI was administered with a bolus dose of lml/kg followed by continuous infusion of another total dose of lml/kg for 6 hrs in SFI group.Hemodynamic including heart rate(HR)and mean arterial pressure(MAP)were monitored and arterial lactate,PH value,oxygen partial pressure(PaO2)and partial pressure of carbon dioxide(PaCO2)were detected at baseline and at 1,3,6 hrs after resuscitation.The concentration of troponin I(TNI),creatine kinase isoenzyme(CK-MB),neuron-specific enolase(NSE),S100B protein,creatinine(Cr),blood urea nitrogen(BUN),intestinal fatty acid binding protein(IFABP),diamine oxidase(DAO),sodium ion,potassium ion,prothrombin time(PT),tumor necrosis factor-a(TNF-a)and interleukin-6(IL-6)in serum were measured at baseline and at 1,3,6 and 24 hrs after resuscitation.Swine were sacrificed at 24 hrs,then the tissues were rapidly obtained to detect apoptosis.Results:1.Baseline characteristics and resuscitation outcome among three groups:Before hemorrhagic shock,there were no significant difference in body weight,ETCO2,HR,MAP and lactate levels among three groups(all p>0.05).Eight of nine swine in TCA group and all swine in Sham and SFI groups were successfully resuscitated.2.Comparison of hemodynamic parameters among three groups:compared with Sham group,HR in the TCA group was significantly increased at 1,3 and 6 hrs and in the SFI group was significantly increased at 1 and 3 hrs after resuscitation(all p<0.05).However,when compared with TCA group,HR in the SFI group was significantly decreased at 3 and 6 hrs after resuscitation(all p<0.05).Compared with Sham group,MAP in the TCA group was significantly decreased at 1 hrs after resuscitation(p<0.05),when compared with TCA group,MAP in the SFI group was increased at 1,3 and 6 hrs after resuscitation,but the difference was not statistically significant(p>0.05).3.Comparison of myocardial injury among three groups:compared with Sham group,the concentration of TNI in TCA group was significantly increased at 1,3,6,24 hrs and in SFI group was significantly increased at 3,6 hrs after resuscitation(all p<0.05).When compared with TCA group,the concentration of TNI in SFI group was significantly decreased at 3,6 hrs after resuscitation(all p<0.05).Compared with Sham group,the concentration of CK-MB in TCA group was significantly increased at 1,3 hrs after resuscitation(all p<0.05).Compared with TCA group,the concentration of CK-MB in SFI group was decreased at 1,3 and 6 hrs after resuscitation,but the difference was not statistically significant(all p>0.05).4.Comparison of brain injury among three groups:compared with Sham group,the concentration of NSE and S100B in the TCA group was significantly increased at 1,3,6 and 24 hrs and in SFI group was significantly increased at 3,6 hrs after resuscitation(all p<0.05).When compared with TCA group,the concentration of NSE and S100B in SFI group was significantly decreased at 3,6 and 24 hrs after resuscitation(all p<0.05).5.Comparison of respiratory function among three groups:there was no statistical difference in PaO2 among the three groups at baseline and at all time points after resuscitation(all p>0.05).There was no significant difference in PaCO2 among the three groups at baseline(p>0.05),PaCO2 in TCA and SFI group were higher than in Sham group at 1,3,6 and 24 hrs after resuscitation,however,the difference was not statistically significant(all p>0.05).6.Comparison of renal injury among three groups:compared with Sham group,the concentration of Cr was increased at 24 hrs after resuscitation in TCA group(p<0.05).In the SFI group the concentration of Cr was increased than in Sham group,but the difference was not statistically significant(p>0.05).Compared with Sham group,the concentration of BUN was significantly increased in TCA group at 1,3,6 and 24 hrs and in SFI group at 3 and 6hrs after resuscitation(all p<0.05).When compared with TCA group,the concentration of BUN was significantly decreased at 3 and 6 hrs after resuscitation(all p<0.05).7.Comparison of intestinal injury among three groups:compared with Sham group,the concentration of IFABP and DAO were both significantly increased in TCA group at 3,6 hrs after resuscitation(all p<0.05).The concentration of IFABP at 3hrs and DAO at 6hrs after resuscitation in SFI group were increased than in Sham group(p<0.05).When compared with TCA group,the concentration of IFABP and DAO in SFI group were both significantly decreased at 3,6 and 24 hrs after resuscitation(all p<0.05).8.Comparison of electrolyte and coagulation function among three groups:there was no statistical difference in concentration of serum sodium ion,potassium ion and PT between the three groups at all time points after resuscitation(all p>0.05).Also,there was no statistical difference within and between groups(all p>0.05).9.Comparison of lactate and PH value among three groups:compared with Sham group,the concentration of lactate was significantly increased in TCA group at 1 and 3 hrs and was significantly increased in SFI group at 3 and 6 hrs after resuscitation(all p<0.05).When compared with Sham group,the concentration of lactate in SFI group was significantly decreased at 1 and 3 hrs after resuscitation(all p<0.05).Compared with Sham group,the PH value was decreased in both TCA and SFI group at 1 and 3 hrs after resuscitation,however the difference was not statistically significant(all p>0.05).Compared with TCA group,the PH value in SFI group was increased at 1 and 3 hrs after resuscitation,but the difference was not statistically significant(all p>0.05).10.Comparison of systemic inflammation response among three groups:compared with Sham group,the concentration of TNF-a was significantly increased in both TCA and group at 1,3,6 and 24 hrs after resuscitation(all p<0.05).Compared with TCA group,the concentration of TNF-? was significantly decreased at 3,6 and 24 hrs after resuscitation(all p<0.05).Compared with Sham group,the concentration of IL-6 was significantly increased in TCA group at 1,3,6 and 24 hrs and in SFI group at 3,6 and 24 hrs after resuscitation(all p<0.05).Compared with TCA group,the concentration of IL-6 was significantly decreased at 3,6 and 24 hrs after resuscitation(all p<0.05).11.Comparison of apoptosis among three groups:compared with Sham group,the tissue apoptosis of heart,brain,lung,kidney and intestine were found in both TCA and SFI group at 24 hrs after resuscitation which was expressed as increased apoptosis index and increased expression of Caspase-3.Compared with TCA group,each tissue apoptosis index was decreased in the SFI group,however the difference was not statistically significant.The expression of each tissue Caspase-3 was decreased,furthermore,the expression in heart and lung were statistically significant(all p<0.05).Conclusions:After traumatic cardiac arrest in a porcine model,the body suffered severe multiple organ injury.Early application of SFI could alleviate the degree of the multiple organ injury.The protective mechanisms may be related to inhibition of systemic inflammation response and mitigation of cell apoptosis. |
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