| Backgroud and Objectives The public health is being increasingly threatenedby cerebrovascular diseases, 80% of which is ischemic cerebrovascular disease(ICVD). Recently, with the proposal of penumbra theory and development ofintra-aterial thrombolysis, outcome of ICVD is greatly improved. However, theincidence of hemorrhagic transformation (HT) increased concomitantly and somestudies showed close relationship between blood pressure and HT. With thedevelopment of intra-vascular interventional therapy, a new problem rises: howshould we manipulate the blood pressure for those with recanalization of formerlyoccluded ateries in order to gain the best outcome and to avoid the occurrence ofhemorrhagic transformation. The aim of our experiment is to investigate the effect ofdifferent levels of blood pressure on the ischemic lesions and complications of ratischemic/reperfusion model, hence to present some useful information for clinicalpractice.Methods 44 rats were randomized to 4 groups: low blood pressure group(LP),normal blood pressure group(NP), high blood pressure group(HP) andurokinase/high blood pressure group(UKHP), with 11 rats in each group. All ratswere anesthetized by enflurane and tmdergone 2-h MCAO by thread followed by24-h reperfusion. Adnephrin was used to enhance the mean arterial bloodpressure(MABP) by 20mmHg for 1 hour at the time point of reperfusion. Sodiumnitroprusside was used to lower MABP by 20mmHg for 1 hour. Physiological salinewas used in the NP group for 1 hour, while both urokinase and adnephrin were usedconcomitantly in the UKHP group. Blood pressure values were recorded carefully atdifferent time points: 5 minutes after femoral catheterization (Fc5min), 15 minutes after occlusion (O15min), reperfusion (Reperf), 30 minutes after reperfusion(R30min) and 60 minutes after reperfusion (R60min), other physiological variablesincluding blood gas, blood glucose, rectal temprature were also recorded.Neurological deficit scores were evaluated at 2 hours after occlusion (O2h) and 24hours after reperfusion (R24h). After 24-hour reperfusion, all rats were decapitatedand brains sliced to analyze infarct volume and to detect visible hemorrhagictransformation. 3 rats in each group were used for immunohistorical andpathological analysis.Results1.There was no significant difference among groups in mean SBP at the time pointof Fc5min, O15min and Reperf (P＞0.05). Mean SBPs at R30min and R60minshowed significant difference among groups (P＜0.05), where mean SBP of UKHPshowed significant difference compared with that of NP and LP(P＜0.05) but showedno significance compared with that of HP (P＞0.05). Paired t-test showed that meanSBP at O15min were significantly different from that of the baseline at Fc5min(t=-2.399, P=0.024), but there were no significant difference between mean SBPs atReperfand baseline (t=-1.611, P=0.119).2. There was no significant difference among groups in MABP at the time point ofFc5min and Reperf (P＞0.05), but it showed significant difference at O15minbetween HP and LP (P＜0.05). MABPs at R30min and R60min showed significantdifference among groups (P＜0.05), where MABP of UKHP showed significantdifference compared with that of NP and LP (P＜0.05) but show no significancecompared with HP (P＞0.05). Paired t-test showed that MABP at O15min weresignificantly different from baseline at Fc5min (t=-2.395, P=0.024), but there wereno significant difference between MABPs at Reperf and baseline (t=0.922,P=0.365)3. There was no significant difference in blood gas, blood glucose, rectaltemperature among groups and over time. 4. Neurological deficit scores at O2h showed no significant difference among groups(P=0.443). However, neurological deficit scores showed significant difference atR24h (F=14.58, P=0.000) , and the LP had the worst scores. Paired t-test showedsignificant difference between neurological deficit scores at O2h and R24h in eachgroup. Neurological deficit scores deteriorated in LP (P=0.047) but improved in NP,HP and UKHP (P=0.076,0.002,0.017 respectively). The results indicated that ahigher blood pressure was associated with a better outcome.5. ANOVA method showed significant difference in infarct volume between HP andLP only (P=0.006). The infarct volume of HP was apparently smaller than that of LP.6. Since there were not enough cases in each group with hemorrhagic transformation,we could not compare the HT rate using chi-square test. But there was indeed atendency that HT occurred more frequently in UKHP (42.8%) than in HP (25%) andLP (28.5%), while the NP had the lowest rate (0%).7. MMP-9-positive cell count showed that there was significant difference betweeneach group except that between the LP and HE UKHP had the largest number ofpositive cells per field (1460±57.7/field) in the cortical area near the ischemiclesion, while the NP had the smallest (293±40.4/field). In the basal ganglia, therewas no significant difference in the number of positive cells among groups.Conclusions1.The rat ischemic/reperfusion model is relatively stable for investigating the impactof different blood pressure levels on ischemic lesions and is of great clinicalrelevance.2. Blood pressure manipulation during reperfusion could affect the outcome of themodel greatly: a higher level of blood pressure was associated with a betterprognosis, while lowering the blood pressure could cause deterioration ofneurological functions.3. Incidence of hemorrhagic transformation seems to associate with different levelsof blood pressure during reperfusion. Blood pressure elevation or lowering might contribute to a higher incidence, with UKHP the highest. Immunohistorical study ofMMP-9 indicated that MMP-9 may play an important role in the hemorrhagictransformation induced by blood pressure fluctuation or urokinase. |
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