Effect Of Acute Hyperventilation On Cerebral Function Of Dogs Undergoing Acute Intracranial Hypertension

Mechanical ventilation plays an important role in medical practice,which involves in clinical anesthesia,ICU and resuscitation.Mechanical ventilation experenced a long time.In 1832,Dalziel developed a negative pressure breathing machine;In 1928, Driker-Shaw developed"iron lung".From then on,a new epoch of mechanical ventilation developed.Within about one century,mechanical ventilation successfully saved a lot of patients'lives.At the same time,more and more doctors thought highly of hyperventilation,but,a new problem occurred,a complication of mechanical ventilation, could produce some important effects on organisms.Hyperventilation means a series of syndrome that ventilation produces once its role surpasses physiological need.When H₂CO₃ level of blood plasma decreased lower limit of normal(PaCO₂＜35mmHg) and PH＞7.45,as called respiratory alkalosis.Acute respiratory alkalosis means respiratory alkalosis takes place within 24 hours.About one century,medical scholars placed much energy to respiratory acidosis,but they paid little attention to respiratory alkalosis because respiratory alkalosis often existed mechanical ventilation and Hysteria Syndrome.At present clinical practice,hyperventilation is frequently used in induction of general anesthesia,extubation,laparoscopic operation,acute intracranial hypertension of trauma and so on,Especially in the traumatic intracranial hypertension.Hyperventilation is often used to reduce intracranial hypertension.Its role of lowering ICP depends on CO₂ chemical regulation in CNS.low CO₂ in blood makes Cerebral vessels constrict,which can reduce cerebral perfusion and ICP,thus,hyperventilation is frequently used to reduce bleeding during operation. Morno-Kellie's principle points out that cranium content consists of brain tissue, cerebral blood volume and cerebrospinal fluid(CSF).Only both cerebral blood volume and CSF is spontaneously regulatable.The alteration of cranium content pressure mainly depends on cerebral blood volume and CSF.But,severe cerebral vasoconstriction does much harm to brain cells.Meanwhile,many studies demonstrated that hyperventilation not only induced cerebral ischemia but also brought wide physiological role such as kaliopenia,acid-base disturbance,etc.Even though many doctors agree on the fact that severe hyperventilation can produce cerbral ischemia,few doctors know how circulatory disorder of brain takes place and how suitable time of hyperventilation is.In addition,they really don't know how electrolytics alter when given hyperventilation.So we establish the intracranial hypertension model of extradural hematoma to make deep study on these problems.Methods25 healthy male dogs,received retro-grade jugular bulb venous catheterization and arterial catheterization,were randomly divided into 5 groups;A,B,C,D and E group(each=5).Dogs but A group were hyperventilated after epidural balloon inflation set up and built up animal model of introcranial hypertention by injecting 3-5ml 0.9%NS into lactoprene balloon of epidura.Dogs'P_ETCO₂ in B,C,D and E group will be maintained 32-45,25-32,25-20 and below 20 mmHg respectively for 60min by adjusting breathing parameters.0.5ml jugular jugular blood and femoral artery blood was taken suction respectively at different P_ETCO₂ period for measuring blood gas,VO₂,DO₂,ERO₂,lactic acid and blood sugar every 10 min when dogs'P_ETCO₂ chalks numerical value Booked.Vs,Vd,Vm,Pi and RI in MCA will be recorded by using Transcranial Doppler(TCD).Meanwhile,cerebral oxygen delivery/supply will be calculated according to blood gas analysis results.1,Data and Grouping25 Healthy male dogs,age from 2 to 4 years,body weight from 13 to 15.5Kg,will raise for one week,fasting for 12hrs,no drinking for 6hs.before experiment,are randomly divided into 5 groups(A,B,C,D and group E,each=5).Dogs in group A were placed a sacculus into epidural cavity but no inflatiing.The sacculus of dogs in any other groups was all inflated as the model of acute intracranial hypertension.All dogs were given 30min normal ventilation and P_ETCO₂ kept 32-45mmHg.2,Anesthetizing and Monitoringsodium pentobarbital according to 30mg/Kg was injected into abdominal cavity for anesthetizing dogs,and afterward intubation was operated.Internal jugular vein punctured under spontaneously breathing for monitoring CVP,infusing fluit and collecting blood.Femoral artery punctured for monitoring blood pressure and collecting blood.Multiparameter monitors continuosly detected body temperature, P_ETCO₂,HR,ECG,iBP and SPO₂.3,Establishing dog's model of intracranial hypertensionEstablish dog's model of intracranial hypertension by adopting epidural sacculus inflation.Place dogs to prone position,ambi-outer ear line 1cm distance between median line was drilled respectively.A trochar in left brain would be intubated to side ventricula to monitor ICP,and a foam rubber sacculus was placed into epidural cavity. Then,3～5ml 37℃physiological saline was injected into the sacculus within 60 seconds and kept ICP 60±3mmHg range.The symptoms of acute intracranial hypertension were as follows:side corediastasis,breathing alleviated or CT Image of occupyed Epidural.4,Targets monitoredAfter kept acute intracranial hypertension for 3hs,0.8mg/kg vecuronium bromide I.v.then given mechanical ventilation.The dogs of group A,control group,without inflation.P_ETCO₂ in group A will be kept from 32 to 45mmHg under ventilatiing.Group B(normal breathing),group C(mild hyperventilation),group D(midrange hyperventilation) and group E(severe hyperventilation)set up the model of intracranial hypertension.After kept P_ETCO₂ normal level for 30min,P_ETCO₂ of B,C,D and group E would be kept 32-45,25-32,25-20 and below 20mmHg respectively for 60min by adjusting breathing parameters.0.5ml jugular blood and femoral artery blood was taken suction respectively every 10min in different P_ETCO₂ period for measuring blood gas,blood lactic acid and blood sugar.Meanwhile,4mL jugular blood will be collected in pre-inflation(T₁),post hyperventilation 2h(T₂),6h(T₃),12h(T₄) 24h(T₅) and 48h(T₆) for measuring content of S100B and CRP.drawn out hydatid fluid from balloon after hyperventilation.Neurological deficits scoring was evaluated at post hyperventilation 2h,6h and 12h.dogs would be put to death for pathological analysis at 48h.5,Monitoring CBFput detecting head of TCD to temple and adjust detecting head untill getting best signal of CMA.Vs,Vd,Vm,Pi and RI in MCA were recorded by using Transcranial Doppler in differently time.meanwhile O₂Ucc,A-VDO₂,Da-juL,ERO₂,Da-jvO₂ and Da-juglu will be calculated by blood gas value.ResultsExcept group A,other any dogs were all established the model of intracranial hypertension and finished this experiment sucessfully.when sacculus inflated,Heart rate got slow,blood pressure increased,respirary frequency reduced and side pupil dilatated (P＜0.05) when compared with pre-inflation.1,Blood gas analysisWith the hyperventilation development,K⁺,Ca²⁺,PaCO₂ and HCO₃^-in arterial Blood decreased gradually.PH increased gradually,there existed a positive correlation between PaCO₂ and K⁺.its coefficient correlation r=0.9196(P＜0.01).Coefficient correlation between PaCO₂ and Ca²⁺ r=0.9196(P＜0.01).CL^-,SaO₂ and Na⁺ kept changeless(P＞0.05).PH decreased with hyperventlation,and got the lowest point 7.11±0.04(P＜0.05) when given severe hyperventilation.SjvO₂ in mild and midrange hyperventilation group kept changeless.But SjvO₂ in group D and group E got lowest point(42±6)%.2,Blood Sugar and Lactic AcidWhen compared with group A,Blood Sugar and Lactic Acid in experimental groups increased rapidly after inflation especially BS and Lac of jugular blood. Da-juglu increased(P＜0.05),Lactic acid in group mild hyperventilation decreased slightly,but severe hyperventilation makes BS and Lac increase(P＜0.05).Da-juL in group D increased sharply,there is significant difference between group A and group D (P＜0.05).3,ICP and HemodynamicsAfter balloon inflated,all dogs'HR decreased quickly,blood pressure and ICP increased.ICP increased from 13±3.4 mmHg in pre-operative to 60±3.0mmHg,there is significant difference when compared with pre-operation(P＜0.05).when value of P_ETCO₂ kept from 25 to 35mmHg,it revealed a positive coefficient correlation of PaCO₂ and ICP r=0.9958(P＜0.01).mild hyperventilation can reduce ICP slightly but its value is much higher than pre-opration.With severe hyperventilation development (P_ETCO₂＜20mmHg),ICP still kept changeless.4,DO₂ and VO₂When inflated,SjvO₂ dcreased quickly with P_ETCO₂.when P_ETCO₂＜20mmHg, SjvO₂ reached the lowest point.Da-jvO₂ decreased gradually with hyperventilation.but Da-jvO₂ in midrange hyperventilation increased significantly when compared with pre-operation or post-inflation(P＜0.05).ERO₂ in mild hyperventilation group changed slightly,but severe hyperventilation made ERO₂ decrease significantly when compared with pre-operation(P＜0.05).5,Transcranial Doppler sonography(TCD)After inflation,TCD showed Vs and Vd got slow greatly after epidural balloon expanded(P＜0.05).PI and RI increased significantly when compared with pre-trauma(P＜0.05).Athough Vs increased in mild hyperventilation,the value of PI and RI in B,C,D and E group grew higher than A group(P＜0.05).when P_ETCO₂＜25mmHg,Vs and Vd got its slowest point and showed much significant difference(P< 0.05) with P_ETCO₂ lowering.When P_ETCO₂＜25mmHg,Vs and Vd got its lowest point and kept changeless when hyperventilation deepened.6,S100B and CRPWhen inflated,S100B and CRP in experimental group increased at different degree (P＜0.05).S100B started to grow in 6h,peaked in 12h(2.08±0.32μg/L),decreased slightly in 24h.The value of S100 in group D grew more than pre-operation and other any groups(P＜0.05).CRP grew rapidly in 2h,peaked in 6h(21.8±2.5mg/L) untill 48h, there was significant difference when compared with pre-inflation(P＜0.05).CRP in group D grew most quickly of all groups,its value reached 29.4±5.7mg/L in T₅(P＜0.05).7,Neurological Deficits Scoring(NDS)After 2h hyperventilation,Neurological Deficits Scoring of all dogs was much high.their score decreased from time to time.NDS in severe hyperventilation group was higher in 2h and 6h than any other groups(P＜0.05 )but no significant difference in 12h(P＞0.05).There was no significant difference between group A,B and C at the sametime(P＞0.05).8,Pathological analysisDogs's brain tissue of area compressed in experimental groups sofetened,swollen and blackened but other side brain tissue kept normal.Under light microscope,brain tissue in compressed area got necrosed mostly.and necrosis band extended to deep brain tissue and got lessened gradually in deep brain area.Necrosis cells in brain of group D diffused distribution.Necrosis was more wider than any other groups.Under electronical microscope,we can see the structure of the necrosis cells get blurred.Mitochondrium vacuolizated and dissolved.Conclusions1,Acute hyperventilation have much important effect on electrolytics and acid base,and it makes PH increase,K⁺ and Ca²⁺ decrease.Blood K⁺ reduced 0.5mmol/L and Blood Ca²⁺ reduced 0.05mmol/L when PaCO₂ reduced every 10mmHg.2,When P_ETCO₂ kept from 25 to 35mmHg,ICP decreased with PaCO₂.when PaCO₂ exceed 35mmHg,ICP dcreased slightly;when PaCO₂ was reduced to 25 mmHg,cerebral ischemia could take place.Severe hyperventilation results in Disequilibrium of O₂ Supply/Need.3,Acute hyperventilation have an important effect on hemodynamics of organism.mild and midrange hyperventilation alleviated hypertension brought about by acute intracranial hypertension. 4,Density of S100Band CRP shows the extent and level of injuried brain,their change have coincidence with NDS.5,Severe hyperventilation resulted in cerebral ischemia lies in Cerebral vessels constricted exceptionally,and obstacle of brain's oxygen intaking plays an important role in cerbral ischemia also.6,Severe hyperventilation delayed palinessthesia time of dogs with acute intracranial hypertension.