| Objective: Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral arterioles to a physiological or pathological dilatory stimulus and is an important mechanism for maintaining constant cerebral blood flow(CBF). This compensatory dilatory capacity of cerebral arterioles is important for constancy of cerebral blood flow, especially when cerebral hemodynamic disturbance occur or partial pressure of oxygen in blood decline. CVR impairment is an independent risk factor for stroke[1,2], therefore, we can identify a high risk population of stroke by detecting their CVR and further evaluate their cerebrovascular regulation capability .Based on the above, it's important to monitor stroke patients CVR in acute stage in order to choose appropriate antihypertensive medications and find a optimal blood pressure to maintain for long term in secondary prevention stage to ensure adequate cerebral perfusion pressure.The existed studies indicated that CVR was significantly impaired in patients with large artery artherosclerotic disease( for example internal carotid artery or intracranial artery occlusive diseases) due to a compensatory dilatory of the cerebral small vessels for long term [3,4]. In patients with large artery occlusive diseases associated with chronic hypoperfusion, it's necessary to maintain normal cerebral perfusion pressure through establishing collateral circulation, compensatory vasodilatation of cerebral small vessels and increasing oxygen intake of brain tissue from blood. Then, there is a poor perfusion, which result in Ischemic stroke, while it's difficult to maintain normal cerebral circulation through all above compensation mechanism. that is CVR in patients with intra-or-extracranial artherosclerosis were exhausted[5]. CVR improvement will reduce occurrence of hypoperfusion stroke.Some animal studies have shown,that statins can upregulate eNOS, decrease platelet activation, augment absolute cerebral blood flow[6], and protect from cerebral ischemia in normocholesterolemic mice[7]. Some researchers supposed that improving endothelial homeostasis through increasing the bioavailability of nitric oxide might be another protection mechanism of statins for stroke, which is independent of their cholesterol lowering effect[8,9].Also, Many clinical trials confirmed the effects of statins on improving CVR of stroke patients [10-12]. However, the relationship between improving CVR and lipid-lowering effect remain obscure.Based on above all, we observed the effect of atorvastatin on CVR in patients with lacunar infarction by breath-holding test of TCD, and further to interpret the mechanism of statin on CVR.Methods: 44 patients with lacunar infarctions (LI) were enrolled this study, all subjects were confirmed the lesions localized in the territory of MCA by brain Computerized Tomography(CT) and/or Magnetic Resonance Imaging(MRI). According to TOAST classification, the patients with large artery atherosclerosis stroke, definite cardiac embolism and other undeterminded etiology were excluded. All patients were performed breath-holding test after acute stage of stroke and the Doppler spectrum and breath-holding index (BHI) were calculated and saved as hardware for analysis offline.Exclusion criteria:1 The patients with large artery occlusive diseases.2 The patients with arteritis, vascular malformation and cardiac embolism or definite embolism resource.3 The patients with poor temporal acoustic windows and not available MCA scan.4 The patients with severe dysfunction in the heart, lung, liver and kidney, or conscious disturbance, severely impaired cognitive function not to communicate normally with.5 The patients with previous statin treatment within 12 weeks.6 The patients with ACEI anti-hypertension medications within 2 weeks.The demographic features of all subjects were registered, medical history and laboratory investigation was record. Routine TCD were performed and the mean arterial velocity (vm) of bilateral MCA and Doppler spectrum were recorded. then the subjects were performed a breath-holding test further.Atorvastatin intervention: All subjects were divided in two groups according to whether they associated with hyperlipidemia, and all patients administrated with 20 mg of atorvastatin per day for a period of at least 3 months. Then the blood sample were taken for cholesterol measurements and breath-holding test were repeated.Method of breath-holding test[23]: The objects were in supine position and keep a 4～5min quiet breath before the test. the probes of TCD was fixed by Spence head frame to show a clear Doppler spectrum, then patients were asked to hold their breath for 30 seconds and while the Doppler spectrum and breath-holding time were recorded. Repeated above process again when the velocity returned to the normal level after 2～3min rest. All results stored in hard disc of TCD equipment and were analyzed off line.The blood flow velocity of bilateral MCA and breath-holding index(BHI) were calculated as the average value of three times.BHI was calculated according to the formula:BHI= [(Vbh-Vr)/Vr]×100%/T [24]Vbh: the maximum mean arterial velocity at the end of breath-holding(cm/s), Vr: the mean arterial velocity at calm respiration(cm/s), T: breath-holding time(s).Statistics analysis: The values of BHI and Vr pre- and post-intervention of atorvastatin in two group patients were compared. The relationship between the lipid level change and BHI improvement after atorvastatin administration were studied by multiple linear regression analysis.Results: 44 patients were enrolled in final analysis (due to 9 patients were lost to follwe-up). Among of them, 18 patients were lacular with hyperlipoidemia ( group HL 40.91%)and 26 patients were lacular without hyperlipoidemia(59.09%). There was no significant difference of the demographic features between the two groups.BHI change in Group HL: There was a significant improvement of bilateral BHI in Group HL after 3-month atorvastatin intervention compared with the initial value. (Left side: 1.29±0.42 vs 1.48±0.36(P=0.003);Right side: 1.32±0.39 vs 1.52±0.33(P=0.001)). This result suggested that atorvastatin treatment improved CVR of HL Group patients.BHI change in Group NHL:BHI were improved through atorvastatin treatment in Group NHL patients, too. Left side: 1.46±0.35 vs 1.58±0.37(P=0.022); Right side: 1.41±0.36 vs 1.55±0.37(P=0.037). there was a significant difference , which suggested that atorvastatin could improve CVR of NHL patients.But the Vr of pre- and post- atorvastatin treatment did not change significantly in Group HL . ( Left side: 47.11±13.93 cm/s vs 48.22±12.47 cm/s,p=0.371; Right side: 47.06±11.00 cm/s vs 49.00±11.98 cm/s,p=0.067)); And Vr remained unchanged after 3 months in Group NHL patients. (left side: 57.23±12.82 cm/s vs 56.88±11.35 cm/s, p=0.756; right side: 53.23±9.01 cm/s vs 54.23±8.82 cm/s,p=0.341. therefore, atorvastatin intervention did not affect the blood flow velocity of MCA.Total cholesterol, triglyceride and LDL-C level were significantly lower after atorvastatin treatment in Groups HL and NHL. In Groups HL, the plasma lipid levels of pre-and post-intervention of atorvastatin were respectively TC: 5.00±1.08 mmol/l vs 3.95±0.80 mmol/l, TG: 1.91±0.67 mmol/l vs 1.35±0.50 mmol/l, LDL-C: 3.27±0.91 mmol/l vs 2.41±0.44 mmol/l,all P-values <0.001.Likewise, the the plasma lipid levels in Groups NHL were TC:4.10±0.65 mmol/l vs 3.35±0.68 mmol/l, p<0.001; TG: 1.14±0.60 mmol/l vs 0.94±0.38 mmol/l, p=0.010; LDL-C: 2.53±0.58 mmol/l vs 2.24±0.26 mmol/l, (P<0.001). HDL-C levels increased significantly after atorvastatin treatment in patients of Group HL (0.95±0.17 mmol/l vs 1.14±0.20 mmol/l, p < 0.001 ) and of Group NHL (1.00±0.23mmol/l vs 1.15±0.23mmol/l, p<0.001. The results showed that atorvastatin therapy also could decreased plasma lipid levels of patients without hyperlipoidemia.Analysis of influence factors of BHI: Regarded Age, gender, hypertension, diabetes mellitus and lipid level as supposed risk factors of BHI. Analyze the relationship between BHI and those factors by multiple linear regression analysis. The result showed that the formulas had no statistics significance. There was not linear relationship between the changes of components of lipid and BHI improvement(left side: F=1.113,p=0.380; right side: F=1.113,p=0.381). The result suggested that atrovastatin treatment can improve BHI in patients with lacunar infarctions, which was independent of its lipid-lowering effect.Conclusion:1 Atrovastatin treatment can improve cerebral vascular reactivity in patients with lacunar infarctions,and this effect was independent of its lipid-lowering effect.2 Atrovastatin intervention did not change the cerebral blood flow of MCA.It's effect on cerebral vascular reactivity may result from improving small-vessle endothelial function.3 Lacunar infarctions patients without hyperlipemia should also take statins to improve their endothelial function. |
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