Experimental Study On Treatment Of Hypertonic Sodium Chloride Hydroxyethyl Starch-40 Injection For The Acute Cerebral Infarction Of Large Area

The acute cerebral infarction of large area is a frequent clinical crisis with a high mortality rate.It is of utmost importance of to diagnose and treat as soon as possible.There are great significances in the experimental study on the acute cerebral infarction of large area by using ideal model for human.The death caused by acute cerebral infarction can be attributed to such main factors as encephaledema,intracranial hypertension and cerebral hernia which are mainly treated with hypertonic dehydrating therapy of mannitol.The adverse effects of large dose use of mannitol(acute renal failure,hypotension and low cerebral perfusion pressure),are increasingly noticeable with the progress of clinical practices,which calls on a safe and effective new drug for reducing intracranial pressure.It has been proved by clinical and experimental research domestically and abroad that hypertonic sodium chloride hydroxyethyl starch-40 injection(HSH) is in favor of the reduction of intracranial pressure,the improvement of cerebral blood flow and the effect of countershock.There are quite a few abroad fundamental researches concerning treatment of HSH for the cerebral injury while few for the acute cerebral infarction of large area.No domestic report on this area is available.The mechanism of above therapy is not totally identified and prospective experimental data for clinically applicable drug dose needed are still unavailable.This paper is to focus on the therapeutical effects and mechanism of the treatment of HSH for intracranial hypertension and encephaledema by using MACO(middle cerebral artery oclussion) model of rat,for the purpose to direct the clinical use of HSH for cerebral infarction,intracranial hypertension and encephaledema.There are two main parts in this research.Part 1:The establishment and evaluation of MACO model of SD ratPurpose:To establish and to evaluate a stable MACO model of rat.Methods:After building MACO model of rat by linefasten,the post-injuried 8 hours intracranial pressure of rat are monitored.Meanwhile,behavioral scores are noted and the area of cerebral infarction are obtained by using TTC(2,3,5-TRIPHENYL-2H-TETRAZOLIUM CHLORIDE) staining.Results:The intracranial pressure is slowly climbing after cerebral infarction,starting after 2 hours,reaching the summit after 6 to 8 hours.TTC staining indicates the large infracted area in right hemisphere with a volume of 189.05±20.40.Conclusions:Cerebral infarction can result in increased intracranial pressure and encephaledema.The vascular cerebral edema is the main pathological change accompanied with cytotoxic cerebral edema and degeneration and necrosis of local neurocytes.MACO model of rat is a stable and reliable model of cerebral infarction which is fit for the later experiments after statistics management.Part 2:Study on therapeutical effects of hypertonic sodium chloride hydroxyethyl starch-40 injection In the acute massive cerebral infarctionPurpose:To inquire the therapeutical effects and the mechanism of hypertonic complex injection for increased intracranial pressure and encephaledema of MACO model. To identify the therapeutical effects of HSH by further observation of apoptosis of infarcted focus as well as ischemic semi-dark band aiming at providing evidences of clinical application for encephaledema after cerebral infarction.Methods:The hypertonic complex injection with certain concentration and the same dose(4ml/Kg) is used on the MACO model of SD rat 4 hours after infarction in each group.The group of physiologic saline(0.9%NaCLsolution 4ml/Kg) is set as blank control while the group of mannitol(4ml/Kg) is set as therapeutic control.The intracranial pressure(ICP) is continuously monitored.Random 6 rats of each group are executed by head-breaking to determine cerebral moisture capacity immediately while the rest 6 rats undergo the same process before surgically intravascular perfusion of paraform(50ml,4%).The brain tissue, drawn from obviously infarction position of frontal and temporal lobes of right hemisphere, is fixed by paraform buffer solution(4%,4℃,pH7.4) for 24 hours.After embedment of wax,the slices with 4μm thickness are made and routinely stained with H-E(hematoxylin and eosin) and TUNEL's.Results:Except the group of physiologic saline,the effects of the drugs start in 15 minutes to 30 hours in the other two groups.During the 4 hours of monitoring,intracranial pressures of last two groups are dramatically decreased at each point,and there is no difference between two groups.Determination of cerebral moisture capacity indicates that the effects of dehydration of last two groups are better than the group of;physiologic saline.Conclusions:HSH has the similar effects of decreasing ICP as mannitol which generate favorable effects against post-infarction encephaledema.There is no difference in starting time between two factors mentioned above.Although HSH has a shorter sustaining time of decreasing ICP than mannitol,it can protect the nervous tissue to certain extent.