DOI: 10.14457/tu.the.2016.1359
title: Hypertensive response and arrhythmic event relate to autonomic modulation and neurovascular oxidative stress in large artery ischemic stroke

description: Large artery ischemic stroke is closely correlated with hypertensive response in 24 hours after onset. In this study, we aim to investigate neurovascular oxidative stress and ANS modulation to test the hypothesis that neurovascular oxidative stress may affect brain-heart axis through ANS modulation and also subsequent pathophysiology of cardiohemodynamic, hypertensive response and arrhythmic event in large artery ischemic stroke. Neurovascular oxidative stress was assessed by NO and H2O2 measurement in plasma. Brain-heart axis control is determined by HRV analysis. Arrhythmic event is determined by QTc using Bazett’s formula method. Healthy control (16) and patients (65) were recruited and studied as follows:- For cardiohemodynamic study, all patients are classified as SBP ≤ 139 mmHg (23), SBP 140-159 mmHg (21) and SBP ≥ 160 mmHg (21) and named group I, group II and group III, respectively. - For hypertensive response study, group I : MABP ≤105 mmHg (30) and group II, MABP ≥ 106 mmHg (35)- For arrhythmic event study, S QTc ≤ 360 ms (36), N QTc 360-390 ms (15) and L QTc ≥ 400 ms (14)All subjects gave inform consent according to the Declaration of Medicine Ethic Committee (MTU-EC-IM-018154). Plasma NO and H2O2 were assessed by electrochemistry method. Five-minutes HRV analysis by lead II EKG were recorded by power lab instrument. QTc is calculated from         . During acute stroke, neurovascular oxidative stress through lower NO level and striking increase in H2O2 are obviously seen. It is notably that significant higher H2O2 is closely correlated with SBP and α1/α2. This finding indicates increasing cardiohemodynamic response during acute stroke is essential for ensuring sufficient blood supply to brain. Greater value of H2O2 may be from H2O2 - derived glia activation during neuronal injury and activation of nNOS as well. On D1 stroke, it is physiological response complexity as seen in higher value of SBP, DBP, MABP, PP and HR in SBP ≥ 160 mmHg group, MABP ≥ 106 mmHg and L QTc group. Shorter PTT is clearly observed. Greater LF/HF ratio with SD2/SD1 indicates an increase in sympathovagal balance from baroreceptor reflex caused by sudden increase in MABP. Meanwhile, decrease in SD1 suggests reducing parasympathetic drive which it, in turn, reflects increasing sympathetic drive. This autonomic control shifts to sympathetic predominant giving peripheral vasoconstriction associated with enormous contractility of heart. Furthermore, less scatter and distribution of SD1, SD2 on Poincare’ plot with low value of sample entropy are evident.For hypertensive response study, NIHSS value of MABP ≥ 106 mmHg group is reduced significantly compared with MABP ≤ 105 mmHg. This result indicates lower stroke severity in this group. Significant higher H2O2 of MABP ≥ 106 mmHg group is evident whereas NO is profound lower value. Taken together, H2O2 - derived glia activation after brain damage producing more H2O2 which, in turn, activates cerebral vasodilation. Stroke recovery from reducing NIHSS value in MABP ≥ 106 mmHg group might partly involve glia activation producing more H2O2 to circulation. Hence, H2O2 plays a vital role in stroke recovery.During D1 – F/U stroke period, MABP of both groups tends, to be low with corresponding SBP, DBP and PP as well. Predominant parasympathetic activity of both groups is evident on D2 and D3 and then it tends to be low in F/U day. Long term ANS modulation in F/U day is observed. Obviously, significant correlation between SBP and α1/α2 (r = 0.45, *; p&lt;0.05) is also found. This result indicates that SBP and MABP play a vital role in hypertensive response by increasing intrinsic and extrinsic factors through α1 and α2 component of DFA analysis which they correspond with cerebral vasodilation by increasing H2O2. Autonomic control shifts toward less parasympathetic activity and reflects greater sympathetic activity governing high blood pressure as we found gradual decrease in power of LF/HF ratio and those in SD2/SD1 on F/U day of both groups.According to hypertensive response from D1 – F/U stroke, ANS modulation by increasing systolic blood pressure and α1/α2 detrended fluctuation analysis under oxidative stress condition leads to ventricular repolarization changes. It is notably that L QTc has increasing blood pressure, pulse pressure and HR that all reflect slow or lower PTT. Higher value of H2O2 in L QTc is evident and shows a significant difference between those in N QTC and S QTc. Profound lower NO is seen in L QTc. It is likely that high degree of neurovascular oxidative stress is found in L QTc. In time domain of HRV, pNN50 (%) of L QTc is very high and reaches a significant level compared with S QTc. In this view, parasympathetic activity is considered but in fact, QTc is depend on time in EKG tracing and it will lead us misunderstand. As we seen in frequency domain of HRV, increasing sympathovagal balance by predominant sympathetic drive with greater LF and lower HF in L QTc. Corresponding with LF/HF ratio, SD2/SD1  is also higher significantly which it reflects well organization and lower value and less irregularity in sample entropy  in L QTc group.  During D1- F/U day, QTc of L QTc tends to be low, which it corresponds with SD2 and sample entropy. Meanwhile, SD1 of L QTc gradual increases from D1 - F/U day indicating greater parasympathetic drive throughout the study.In conclusion, under neurovascular oxidative stress during acute stroke, cerebral endothelial dysfunction and vascular inflammation associated with brain damage induced glia activation and subsequent cardiohemodynamic and hypertension complexity response through autonomic control of brain-heart axis are demonstrated throughout D1-F/U day study. Arrhythmia is very common in stroke by variation of QTc. Long QTc is obviously observed by ANS modulation with well-organized control and response through increasing parasympathetic activity. Less severity of post stroke as shown by NIHSS is also found in hypertensive response and L QTc groups.