| Hemorrhagic shock is a clinically severe case,caused by massive blood loss,characterized by the shortage of effective circulation blood,tissue perfusion decrease.The incidence and mortality rate are high in peacetime and war.At present,the study of hemorrhagic shock focuses on the mechanism of hemorrhagic shock at normal temperature and the targeted prevention and control measures.There are few studies on the pathophysiological characteristics of hemorrhagic shock in high tempe rature environment,and the related damage mechanism is not clear at present.With the global warming,the number of areas with high temperatures is gradually increased.In the past,many studies confirmed that high temperature can induce the body environment disorders,tissue and organ damage.There are more studies focusing on the damage mechanism and treatment for high temperature environment induced damage.However,at high temperature,its pathophysiological characteristics and treatment strategy for hemorrhagic shock remains unclear.In this study,the pathophysiological characteristics of hemorrhagic shock rats including internal environment,tissues and organs function,stress inflammatory factors,mitochondrial function and structure,and treatment regimens in high temperature enviroment were analyzed.The specific contents included four parts:(1)changes of core temperature of rats under different ambient temperature;(2)changes of survival time of rats after hemorrhagic shock under high temperature enviroment;(3)pathophysiological characteristics and mechanism of hemorrhagic shock at high temperature enviroment;(4)treatment strategy for hemorrhagic shock rats at high temperature enviroment.Experiment methods:SD rats were placed at high temperature enviroment for 12 hours,and hemorrhagic shock model at high temperature was prepared by bleeding.The changes in Na+,K+,plasma osmotic pressure,arterial blood gas,hemorheology,organ function(heart,liver and kidney),ACTH,GCS,IL-6,TNF-?,ROS,MDA,content of ATP,ATPase activity,were observed at baseline,at the end of the bloodletting and at 1 hour after the bloodletting.The changes of mitochondrial structure before and after shock were observed by transmission electron microscopy(TEM).Research contents:Part One: Changes of core temperature in rats under different temperatureRats were placed at different temperatures(38°C,36°C,34°C,25°C).The core temperature of the rats was measured at an interval of 0.5 hour using a medical thermometer.And the observation was sustained for 12 hours.Part Two: Changes of survival time after hemorrhagic shock in rats under high temperature environment.1.Rats were placed in different temperature environments(25°C,32°C,34°C,36°C,38°C)for 12 hours.After 40% of the total blood loss,the survival time and 72 h survival rate of were observed.2.Rats were placed at normal temperature(25°C)and high temperature(34°C)for 12 hours.The changes of survival time and 72 h survival rate were observed after 30%,40% and 50% of total blood loss.Part Three: Pathophysiological characteristics of hemorrhagic shock in high temperature environment1.Rats were placed at normal temperature(25°C)and high temperature(34°C)for 12 hours.After 40% of the total blood loss,the changes of blood electrolyte(Na+,K+),osmotic pressure,arterial blood gas and hemorheology were observed before the shock,at the end of the bloodletting and at 1 hour after the bloodletting.2.Rats were placed at normal temperature(25°C)and high temperature(34°C)for 12 hours.After 40% of the total blood loss,the changes of cardiac output(CO),heart index(CI),stroke index(SI),aminotransferase(AST),alanine aminotransferase(ALT),renal function(CREA)were observed before the shock,at the end of the bloodletting and at 1 hour after the bloodletting.3.Rats were placed at normal temperature(25°C)and high temperature(34°C)for 12 hours.After 40% of the total blood loss,the changes of stress factors(ACTH,GCS)and inflammatory factors(IL-6,TNF-?)were observed at baseline,at the end of the bloodletting and at 1 hour after the bloodletting.4.Rats were placed at normal temperature(25°C)and high temperature(34°C)for 12 hours.After 40% of the total blood loss,the changes of ROS,MDA,ATPase activity,ATP content and myocardial mitochondrial structure in rats were observed before the shock,at the end of the bloodletting and at 1 hour after the bloodletting.Part Four: Treatment strategy of hemorrhagic shock in high temperature environment1.Rats were placed at normal temperature(25°C)and high temperature(34°C)for 12 hours.After 40% of the total blood loss,rats were resuscitated with different temperatures of Ringer's solution(37°C,25°C,10°C,4°C)in 2 times of the amount of blood loss,the survival time and 72 h survival rate were observed.2.Rats were placed at normal temperature(25°C)and high temperature(34°C)for 12 hours.After 40% of the total blood loss,rats were treated with 4°C lactate Ringer's solution(LR)combined with Mdivi-1,the inhibitor of mitochondrial fission protein drp1(1mg / kg),and the survival time and survival rate were observed within 72 hours.Main results:Part One: Changes of core temperature in rats under different temperatureAt high temperature,the core body temperature of rats was increased rapidly after 30 minutes.The maximal core temperature of the rats was 40.6°C after 3 hours at 38°C and then fluctuated between 39.8°C and 40.6°C.After 30 minutes at 36°C environment,the core temperature reached the highest(40.0°C)and then fluctuated between 39.4°C and 40.0°C.After 2 hours in the environment of 34°C,the highest core temperature(39.4°C)was attained followed by a gradual decrease.After 6 hours,there was no difference between the core body temperature and the body temperature in the normal temperature group(25°C),and all were between 38.4°C and 38.8°C.Part Two: Changes of survival time after hemorrhagic shock in rats under high temperature1.For the same blood loss(40%)and different ambient temperatures(25°C,32°C,34°C,36°C,38°C),it was found that the survival rate of rats was significantly decreased with the increase of ambient temperature.2.In the case of different blood loss(30%,40%,50%),the death time of the rats in the high temperature group(34°C)was significantly longer than that in the normal temperature group(25°C),and the survival rate was decreased.The amount of blood loss in rats was increased with a decrease in the survival rate.Part Three: Pathophysiological characteristics of hemorrhagic shock in high temperature environment1.Electrolyte,osmotic pressure: Compared with the normal temperature group(25°C),the electrolyte and osmotic pressure of the rats in the high temperature group(34°C)were partially changed.The concentration of Na+ and plasma osmolality in the high temperature group(34°C)were significantly higher than those in the control group(P<0.05).After the hemorrhagic shock,the concentration of Na+ and K+ in the high temperature group was further increased(P <0.05),and the plasma osmotic pressure did not change significantly.Arterial blood gas: Compared with the normal temperature group(25°C),the changes of arterial oxygen partial pressure(PO2)and carbon dioxide partial pressure(PCO2)in the arterial blood of the high temperature group(34°C)changed significantly.The levels of PO2 and PCO2 in the high temperature group were significantly decreased(P <0.01).After hemorrhagic shock,PCO2,HCO3-decreased(P <0.05).Hemorheology index: Compared with the normal temperature group(25°C),the rats in the high temperature group(34°C)changed obviously before the shock.The shear rate of whole blood viscosity was decreased in the high temperature group(34°C)(P<0.01).After hemorrhagic shock,there was no difference in shear rate between the two groups.2.Cardiac Function: Compared with the normal temperature group(25°C),the cardiac function of the rats in the high temperature group(34°C)was compensatorily increased before the shock,and the cardiac function was impaired in the high temperature group after hemorrhagic shock.The cardiac output(CO)and heart index(CI)were increased by 25.1%(P<0.05)and 31.3%(P<0.05)in the high temperature group(34°C).After the hemorrhagic shock,CO and CI in the high temperature group were decreased by 63% and 63% respectively.The CO and CI of the rats in the normal temperature group were decreased by 44% and 48% respectively.Liver and kidney function: Compared with the normal temperature group(25°C),the liver and kidney function of the high temperature group(34°C)had no obvious change before the shock,and the degree of damage after hemorrhagic shock was more serious.The AST and ALT in the high temperature group were increased by 24.7%(P<0.05)and 44.1%(P<0.05)respectively,and the increase of CREA was 50.7%(P<0.01)in the high temperature group,which was significantly higher than that in the normal temperature group.3.Stress factor: Compared with the normal temperature group(25°C),the high temperature group(34°C)rats were in high stress state before shock,and the level of stress factor was more obvious after hemorrhagic shock.The ACTH and GCS of the rats in the high temperature group were increased by 43.4%(P<0.05)and 114.5%(P <0.01).The levels of ACTH and GCS in hyperthermia group were significantly higher than those at normal temperature group(P<0.01)and 81.8%(P<0.01).Inflammatory factor: Compared with the normal temperature group(25°C),the inflammatory factors of the rats in the high temperature group(34°C)had been significantly increased,and the increase was more obvious after hemorrhagic shock.The levels of IL-6 and TNF-? were increased by 15.6%(P <0.05)and 16.6%(P <0.01)in the high temperature group.After hemorrhagic shock,the levels of IL-6 and TNF-? in the high-temperature group were significantly higher than those in the normal temperature group 13.2%(P <0.05)and 13.9%(P <0.01)respectively.4.Mitochondrial function: Compared with the normal temperature group,the mitochondrial function of the rats in the high temperature group was damaged,and the injury was more serious after hemorrhagic shock.The rats in the high temperature group were 41.7% lower than those in the normal temperature group(P <0.05).ROS,MDA did not change significantly.After hemorrhagic shock,ATP content decreased by 43.0%(P <0.05)and ROS and MDA increased by 23.5%(P <0.05),61.5%(P <0.05).Mitochondrial structure: The morphological structure of myocardium mitochondria was significantly lower in shock group before and after shock.After the hemorrhagic shock,the mitochondrial ridge structure of the high temperature group was dissolved,broken,vacuolized,and the dissolution of the filament was observed.The degree of mitochondrial damage was more severe than that of the normal temperature group.Part Four: Treatment strategy of hemorrhagic shock in high temperature environment1.The survival time and survival rate of the rats were prolonged after resuscitation of different temperature of LR as compared to control group.4°C of LR had the best effective,the survival rate was increased by 71.4% as compared to 25? LR resuscitation.2.The addition of Mdivi-1(1 mg/kg)in 4°C of LR resulted in a further prolonged survival time of the shock in high temperature environment compared with pure fluid resuscitation.Conclusion:1.High temperature contributes to the more and rapidly death of rats with hemorrhagic shock.2.The cause of rapid death of hemorrhagic shock in high temperature environment is closely related to heat stress induced-organ function damage.3.Cryogenic fluid resuscitation combined with Mdivi-1 may be an effective treatment for hemorrhagic shock in high temperature environments. |
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