Cerebrovascular Carbon Dioxide Reactivity Of Acute Ischemic Stroke Patients And The Efficacy Of Butylphthalide Intervention

Objective: Cerebrovascular Carbon dioxide reactivity (CO2R) refers tothe ability that changes with Carbon dioxide pressure level, the cerebralarterioles and capillaries compensatory expand or contract, to maintainrelative stability of the cerebral blood flow or regulate the cerebral blood flowin order to adapt the need of brain function. As the important indicators ofcerebrovascular regulation potential and cerebrovascular reserve capacity, ithas a closely relationship with the occurrence, recurrence and prognosis ofstroke. So improving CO2R of stroke patients can reduce the risk of recurrenceof stroke and make its prognosis better. Studies have confirmed, some drugswhich have the ability of promoting collateral circulation open, angiogenesis,or improving vascular smooth muscle systole and diastole can improve CO2R.Based on this, our study used the domestic first class new drugsButylphthalide and Sodium Chloride Injection as the study drug. And thepatients’ CO2R were test by transcranial doppler (TCD) ultrasonographyafter autologous CO2inhalation. In the end, we evaluated the effect ofButylphthalide and Sodium Chloride Injection for cerebrovascular CO2R ofthe acute ischemic stroke (AIS) patients. At the same time, recorded thechanges of the Vm in the lesion side middle cerebral artery(MCA) before andafter Butylphthalide or basal treatment for different types of stroke, analyzedthe action mechanism of Butylphthalide.Methods: Acute cerebral infarction and transient ischemic attack (TIA)patients who were hospitalized in the Department of Neurology, ThirdHospital of Hebei Medical University during November2012to December2013were collected. Based on the classic TOAST etiology classification, wescreened large artery atherosclerosis(LAA) and small-artery occlusion(SAO)stroke patients as the research objects. All of the patients were routinely taken TCD and autogenous CO2inhalation test before treatment, to be evaluated theCO2R of the lesion side middle cerebral artery(MCA), recorded the Vm，andreviewed the CO2R and Vm of the same side MCA after the treatment.All subjects were regularly recorded gender, age and NIHSS score onadmission, and recorded the vascular risk factors in detail, including thehistory of hypertension, diabetes mellitus, hyperlipidemia, stroke, coronaryatherosclerotic heart disease and history of smoking and drinking.All subjects were randomly divided into butylphthalide interventiongroup and basal treatment group. The basal treatment was the drugs in thestroke guidelines. The butylphthalide intervention group was based on thebasal treatment given intravenous infusion Butylphthalide and SodiumChloride Injection25mg (100ml), two times a day. The course of thetreatment was7-14days.The method of autogenous CO2inhalation test: subjects laid down,quietly breathed4-5minutes, used the Multi-Dop X TCD detector ofGermany’s DWL company.2MHz probes were used to monitor the MCAblood velocity of lesion side in the depth of50mm-65mm. When thevelocity steady, special head fixed frame with ultrasonic elastic probe werefixed to the subjects. A special mask with CO2flow detector connected, themask sensor hole connected with CO2sensor. The mean blood flow velocity(Vm) and end-tidal CO2(ETCO2) concentration on basic state were recorded.Then connected a ventilator airway that is2meter length, to increasephysiological dead space, in order to inhale high concentrations of CO2,whensubjects felt suffocated(1minute-2minutes), recorded Vmand ETCO2at thistime.Statistical processing: Analyzed by SPSS13.0software, Count data wasshown as positive cases, and be analysised by chi-square test. Measurementdate were represented by mean±standard deviation, made normality andhomogeneiy of variance test. Compared between before and after thetreatment, when it was normal distribution, used paired-samples T test, but ifnot, used Wilcoxon signed rank test. Compared between two groups, when it accord to normal distribution, used indepented-samples T test, and if not, usedMann-Whitney U test. P＜0.05was considered statistically significant.Results:1109AIS patients are included. The average age of all subjects is(59.29+10.75) years, and the number of male patients is85(78.98%), femalepatients (21.02%). The mean CO2R of all the AIS patients at the baseline statewas (1.78+0.55)%/mmHg, Which is significantly dropped than the meanCO2R of the healthy persons (2.45+0.45)%/mmHg, the difference hasstatistical significance(t=-6.814, P <0.001). Among these, the number ofLAA patients is74(67.89%), SAO patients is35(32.11%). The mean CO2R ofLAA patients at the baseline state is (1.70+0.54)%/mmHg, The meanCO2R of SAO patients at the baseline state is (1.96+0.54)%/mmHg, thedifference has statistical significance (t=-2.354, P=0.020).2The butylphthalide intervention treatment group includes53patients,and the basal treatment group includes56patients. After treatment, the CO2Rof both the butylphthalide intervention treatment group and the basal treatmentgroup are significantly improved, the respectively are [（2.13±0.73)%/mmHgVS(1.74±0.52)%/mmHg，Z=-4.356，P <0.001]and[(2±0.64)%/mmHgVS(1.82±0.58)%/mmHg，t=-2.736，P=0.008]. Comparison between thetwo groups, the degree of improvement with butylphthalide intervention ismore significant, the difference has statistical significance [(0.39±0.54)%/mmHg VS (0.18±0.49)%/mmHg，t=2.077，P=0.040].3In the74LAA patients, there are34patients in the butylphthalideintervention treatment group, after treatment, the mean Vm（78.37±27.54）cm/s is significantly decreased than before, which is（84.7±37.20）cm/s,the difference has statistical significance (Z=-2.223, P=0.026). But for the40patients in the basal treatment group, there are no statistical significancebetween before and after treatment [（91.58±38.61）cm/s VS（90.50±39.01）cm/s，Z=-0.282，P=0.778]. In the35SAO patients, there are19patients in thebutylphthalide intervention treatment group, after treatment, though the meanVmshown a trend of increase than before, there is no statistical differences. Conclusion:1To all the AIS patients, the CO2R of the lesion side MCA aresignificantly impaired when compared with normal persons. Among these, theCO2R of the LAA patients are more significant damaged than the SAOpatients.2The treatment of Butylphthalide and Sodium Chloride Injection for theacute phase of the AIS patients, can significantly improve their CO2R of thelesion side MCA.3The acting site of the Butylphthalide and Sodium Chloride Injectionmay be not only on the small artery, it may also help the LAA patients opentheir collateral circulation of their lesion side, thereby reducing the load of theMCA in the lesion side, or may be have the effect of endothelial protection inorder to dilate blood vessels for the MCA in the lesion side of LAA patients.