| Part one.Characteristics of cerebral autoregulation in patients with ischemic stroke after intravenous thrombolysis Background and objective:After acute ischemic stroke,a series of pathophysiological changes will occur in local brain tissue due to ischemia and hypoxia,including the destruction and repair of vascular structure and function.The structural and functional integrity of cerebral vascular endothelial cells is closely related to the stability of dynamic cerebral autoregulation(dCA).It has been shown that dCA was significantly impaired after acute ischemic stroke.However,for patients receiving intravenous thrombolysis,the change of dCA after stroke onset is not clear.In this section,we aimed to clarify the characteristics of dCA in patients with intravenous thrombolysis,and lay a foundation for the clinical application of dCA.Methods:This was a prospective clinical study.Patients with a diagnosis of acute ischemic stroke after intravenous thrombolysis were included consecutively.Cerebral blood flow velocity was monitored by transcranial doppler sonography and arterial blood pressure was monitored by Finometer at 3 different time points(1-2 days,3-4 days and 7-8 days after stroke onset).Transfer function analysis model was used to evaluate dCA.Healthy adults matched with age and gender of acute ischemic stroke patients were selected as controls.The changes of dCA over time,and the differences between different ischemic stroke subtypes,as well as between the affected and unaffected sides were analyzed.Results:Finally,223 patients(age 58.57 ± 10.29 years,187 males [83.9%])with intravenous thrombolysis,including 79(35.4%)with large-artery atherosclerosis(LAA)patients,126(56.5%)with small artery occlusion(SAO)and 18(8.1%)with stroke of undetermined etiology(SUE)and 223 healthy controls(age 59.32 ± 11.14 years,187 males [83.9%])were enrolled.We found that dCA in unaffected(27.83±12.41degree)and affected(26.64±14.80degree)sides in LAA patients were significantly decreased comparing with SAO patients(unaffected sides,36.82±10.75degree;affectedsides,36.06±11.08degree)1-2 days after onset,no difference was found at other time points.DCA was similar in affected and unaffected sides regarding different subtypes of stroke.In addition,dCA did not change over time(1-2days,32.97±20.08 degree in unaffected sides,31.85±20.73 degree in affected sides;3-4days,31.63±18.99 degree in unaffected sides,30.79±20.05 degree in affected sides;7-8days,33.47±18.97 degree in unaffected sides,32.62±21.72 degree in affected sides)and was significantly lower than that of healthy controls(50.31±15.46 degree).Conclusion:DCA in patients with ischemic stroke after intravenous thrombolysis decreased significantly at acute phase after stroke onset,and did not fluctuate obviously over time.DCA was impaired both on affected and unaffected sides in different stroke subtypes,and the impairment was the most sever in patients with LAA.Part two.The association between cerebral autoregulation and clinical prognosis in patients with ischemic stroke after intravenous thrombolysis Background and objective:In the first part,we identified that the impairment of dCA was prolonged in patients with ischemic stroke after intravenous thrombolysis.Previous studies have showed that dCA was closely associated with clinical outcomes in patients with acute ischemic stroke.However,for patients receiving intravenous thrombolysis,as discussed in part one,recombinant tissue plasminogen activator(rt-PA)may damage dCA to some extent,it was not clear whether the relationship between dCA and prognosis changed after rt-PA therapy in the hyperacute phase.Methods:In this section,patients with acute ischemic stroke after intravenous thrombolysis enrolled in the first part of the study were investigated.Modified Rankin Scale(m RS)was evaluated 90 days after onset by telephone.Good prognosis was defined as m RS?2.The differences of dCA between the good prognosis group and the poor prognosis group was compared.The relationship between dCA parameters and clinical prognosis was analyzed using multivariate binary logistic regression model.Results:A total of 223 patients with acute ischemic stroke receiving intravenous thrombolysis,including 150(67.3%)patients with good prognosis and 73(32.7%)patients with poor prognosis and 223 healthy controls were enrolled.We found that dCA in patients with both good and poor prognosis were decreased comparing with healthy controls.DCA measured 1-2 days after onset in good prognosis group were significantly higher comparing with poor prognosis group,but the difference disappeared in the 3-4 and 7-8 days.When considering dCA as continuous variables,dCA 1-2 days after onset in both unaffected(Odd ratios [OR] 0.965,95% confidence interval [CI] 0.946-0.985,p < 0.001)and affected(OR 0.959,95% CI 0.939-0.980,p< 0.001)sides were associated with clinical outcomes.When considering dCA as X dichotomous variables,phase difference(PD)?30.55 degree inunaffectedsides(OR0.476,95% CI 0.238-0.952,p = 0.036),PD?29.51 degree inaffectedsides(OR 0.275,95% CI 0.130-0.584,p < 0.001)1-2 days after onset and PD?30.20 degree inunaffectedsides(OR 0.390,95% CI 0.198-0.768,p = 0.006)3-4 days after onset were independent predictors of good prognosis,respectively.Conclusion:In patients with ischemic stroke after intravenous thrombolysis,dCA impaired on both sides at 1-2 days,3-4 days,7-8 days.DCA of 1-2 days after onset on both sides were associated with clinical outcomes.PD?30.55 degree inunaffectedsides,PD?29.51 degree inaffectedsides1-2 days after onsetwere independent predictors of good prognosis,respectively.Part three.The influencing factors of cerebral autoregulation in patients withischemic stroke after intravenous thrombolysis Background and objective:DCA is the result of multiple neurohumoral regulation in the body.As mentioned above,dCA impairment after stroke has been widely confirmed,however,the specific mechanism is not clear.Neuromodulation is an important part of dCA regulation.Nevertheless,up to now,the conclusions of studies in animal or clinical experiments on sympathetic nerve and dCA regulation are controversial.Therefore,the relationship between them is still remained unknown.In this section,we will explore the influencing factors of dCA impairment in patients with ischemic stroke by studying the neurogenic theory and clinical factors that are closely related to dCA.Methods:Patients diagnosed with acute ischemic stroke after intravenous thrombolysis and healthy adults included in the first part of the study were investigated.Since the second part of the study found that dCA measured 1-2 days after onset was associated with clinical outcomes,in this part,we will focus on the influencing factors of dCA on1-2 days.Glycated hemoglobin,triglycerides,cholesterol,low-density lipoprotein cholesterol,creatinine,uric acid,high-sensitivity C-reactive protein,homocysteine and other laboratory indicators were measured the first morning after admission,that is,within 24 hours after onset.Heart rate variability(HRV)was monitored within 48 hours after intravenous thrombolysis.HRV was calculated as power of low frequency(LF,0.04-0.15 HZ)and high frequency(HF,0.15-0.4 HZ)in normalized units(LF[un.] and HF [un.])and the ratio of LF and HF(LF/HF),all of which reflect the relative activity and balance of sympathetic and parasympathetic nervous systems.Linear regression models were used to analyze the association between clinical factors,HRV indices in frequency domain and dCA.Results:Eight patients with severe arrhythmia and 12 patients with ectopic beats more than 20% were excluded.Finally,203 patients were enrolled.LF(un.)and LF/HF were significantly increased,and HF(un.)was significantly decreased in intravenous thrombolysis patients compared with controls,indicating that the sympathetic activity increased,the parasympathetic activity decreased,and the balance between sympathetic and parasympathetic nervous systems was broken in patients with ischemic stroke after intravenous thrombolysis.Univariate linear regression analysis showed that age and diabetes were negatively correlated with dCA,and LF(un.)was positively correlated with dCA in affected sides(? = 0.148,p = 0.036),HF(un.)was negatively related to the affected side dCA(? =-0.148,p =0.036).Multivariate linear regression indicated that age was negatively correlated with dCA in both unaffected and affected sides,while LF(nu.)was positively correlated with dCA in affected sides(? = 0.144,p = 0.030),indicating that parasympathetic nervous systems may play a role in dCA regulation.Conclusion:Age was negatively correlated with dCA in patients with ischemic stroke after intravenous thrombolysis.Abnormal autonomic nervous activity may be one of the influencing factors of dCA impairment in patients with ischemic stroke after intravenous thrombolysis. |
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