The Development Of Neck Cooling Device And Its Protective Function Of Brain In Cardiopulmonary Resuscitation Rabbits

Brain injury after cardiopulmonary resuscitation (CPR) is the bottleneck of the finaloutcome of the patients after cardiac arrest(CA),and its fundamental mechanism is globalcerebral ischemia-reperfusion injury. Mild hypothermia is currently the only brainprotection measures which is certified by a large number of clinical studies and stronglyrecommended by a number of professional associations. Selective head cooling has getbeen more and more attention for its low required cooling energy,small size of device andsmall interference of systemic, but clinical cooling therapies have more or lessdefects.Further more, therapeutic hypothermia after CPR often lag behind the process ofreperfusion of the brain,although effective,but therapeutic target focuses on the latter partof the inflammatory response and apoptosis and misses the early treatment window ofcerebral reperfusion injury.The neck has become the unique conditions of selective braincooling:(1) the intracranial blood vessels(carotid and vertebral arteries) must be throughthe neck;(2) the carotid artery and its branches are relatively superficial, and neck does nothave a hard shell, so the cooling effect can be achieved through heat exchange.Inaddition,studies reported that,compared with cooling after CPR,hypothermia during CPRhave a significant effort on brain protection. We hypothesis:(1) if we rapidly reduce thetemperature of the neck, and then the temperature of the intracranial blood flow will reducethrough heat exchange, so the temperature of the brain tissue will rapidly reduce atlast,(2)Compared with the treatment of the conventional mild hypothermia after CPR(surface cooling), starting deep and fast neck cooling while CPR will pre-cool blood whichis about to enter brain tissue before ROSC,quickly reduce brain temperature after ROSC,and so as to achieve the concept of non-invasive brain hypothermia reperfusion,attain thepurpose of reducing brain damage after cardiac arrest significantly,improving the functionof the CNS and increasing survival rate.Part Ⅰ The development of a neck cooling device and observation of surface coolingeffect of the deice. Objective To develope a neck cooling device which can be used to the rabbits and observethe cooling effect.Methods We design neck cooling device using the principles of semiconductor coolingand heat conduction between tissues.We observe the cooling effect by using thermometerprobe for four times,andthe observation interval is1minute and the total time is60minutes.Results Finally, we develop a neck cooling device which can be used for rabbits.Byobserving the cooling effect we discover the temperature of surface of cooling devicereduces to below0℃within5minutes and then maintains at about-4℃.Conclusions The cooling device we design has the features of Developed fast cooling rateand clear cooling effect.Part Ⅱ The observation of the brain cooling effect of the neck cooling device used inrabbits and safety.Objective To observe the cooling effect of the neck cooling device used in rabbits andsafety.Methods Five anesthetized New Zealand rabbits were orally intubated.We observe thetemperature of brain,neck and rectum when the cooling device is used in the neck of therabbits for60minutes,monitor hemodynamics and respiratory function, and then take theskin of the neck for HE staining.Results After60minutes cooling, temperature of brain,neck and rectum decrease5.7±1.1℃,7.9±1.4℃and3.9±0.7℃respectively.Compared with temperature of rectal,temperature of brain decreases significantly, and with the prolongation of the cooling time,brain-rectum temperature gradient becomes more and more obvious,from0.5±0.3℃to-1.3±0.9℃. The parameters of hemodynamic and respiratory function have nosignificant differences, and no obvious abnormal HE staining of the skin of the neck isobserved.Conclusions Neck cooling device can quickly reduce the temperature of brain of rabbitand have a small effect on body temperature.It also have a high security. Part Ⅲ The observation of the protective effect of rabbit brain whenimplementation of neck cooling at the beginning of CPR.Objective To observe the protective effect of rabbit brain when implementation of neckcooling at the beginning of CPR.Methods Twenty-four anesthetized New Zealand rabbits were orally intubated，submittedto4minutes of untreated ventricular fibrillation, and then randomized to neck coolinggroup(n=8) which implements neck cooling at the beginning of CPR,whole body coolinggroup(n=8) which implements systemic cooling by ice and fan at60minutes afterCPR,and control group(n=8) which only implements the conventional CPR with notemperature intervention.We observe successful CPR rate, survival time, brain,neck andrectal temperature within4hours,the change of hemodynamics and respiratory function,change of NSE within72hours,and NDS scores at24hours.Results Compared with whole body cooling group,Neck cooling group can reduce braintemperature significantly during CPR and after CPR,reach the lowest value (29.9±0.7℃) at60minutes after CPR,and have a small effect on rectal temperature(35.6±0.7℃). Thebrain temperature are37.1±0.8℃,37.9±0.2℃, and37.6±0.7℃at the time of chestcompressions press for4minutes,and the neck cooling group and whole body coolinggroup have significant difference(P=0.044).The cooling rate of brain temperature in threegroups are0.14±0.70℃/min,0.06±0.02℃/min,and0.02±0.01℃/min,the cooling rate ofthe neck cooling group are faster than the other two groups, and have a significantdifference (P <0.05). The cooling rate of rectal temperature in three groups are0.04±0.01℃/min,0.06±0.01℃/min,and0.02±0.01℃/min,the cooling rate of the wholebody cooling group are faster than the other two groups, and have a significant difference(P <0.05).No significant differences were observed in parameters of hemodynamic andrespiratory function (P>0.05). However, we found that hemodynamic parameters of neckcooling group reached the lowest value at60min after ROSC,and the change of MAP andbrain or neck temperature are closely related (R2=0.75,0.90). Compared with control group,neck cooling group and whole body cooling group have a significant differences in the values of NSE at3h and6h after ROSC (P <0.05).No significant differences were alsoobserved in24hours NDS scores, survival time and the rate of successful CPR(P>0.05).Conclusions Implementation of neck cooling at the beginning of CPR can reduce braintemperature, and have a small effect on the body temperature.It also can reduce braintemperature at the time of chest compressions press for4minutes,and achieve reperfusionof non-invasive hypothermia.But too low brain temperature may lead to decrease the MAP,resulting in low perfusion of the tissues and organs after CPR, and thus affecting theprognosis of the rabbit,which remains to be further improved cooling devices and coolingprogram.