Katedra i Klinika Neurologii Pomorskiej Akademii Medycznej w Szczecinie ul. Unii Lubelskiej 1, 71-252 Szczecin
Kierownik: prof. dr hab. n. med. Przemysław Nowacki
1 Zakład Biochemii Katedry Biochemii i Chemii Medycznej Pomorskiej Akademii Medycznej w Szczecinie al. Powstańców Wlkp. 72, 70-111 Szczecin
Kierownik: prof. dr hab. n. med. Dariusz Chlubek
Streszczenie
Wstęp: Celem pracy była próba odpowiedzi na pytanie, czy wahania ciśnienia tętniczego u chorych z nadciśnieniem tętniczym, w ostrej fazie niedokrwiennego udaru mózgu, bez istotnych hemodynamicznie przeszkód w przepływie krwi w tętnicach szyjnych i proksymalnych odcinkach tętnic śródczaszkowych prowadzą do zaburzeń krążenia w tęt-nicach przednich mózgu (ACAs), ocenianego za pomocą przezczaszkowej ultrasonografi i Dopplerowskiej (TCD).
Materiał i metody: Do badania włączono 62 chorych w średnim wieku 65,16 ± 11,52 lat, z nadciśnieniem tętni-czym, w ostrej fazie pierwszego w życiu niedokrwiennego udaru mózgu. Analizowano ciśnienie skurczowe (SBP), ciśnienie rozkurczowe (DBP), średnie ciśnienie tętnicze (MBP). Na podstawie uzyskiwanych widm prędkości prze-pływu krwi obliczano następujące parametry: prędkość średnią (Vmean), wskaźnik pulsacji (PI), wskaźnik oporu (RI).
Wyniki: Istotny spadek wartości SBP, DBP i MBP miał miejsce między 1. a 2. dobą obserwacji, nie obserwowano korelacji między spadkiem ciśnienia tętniczego a parame-trami przepływu w ACAs.
Wnioski: U chorych z nadciśnieniem tętniczym oraz bez istotnych przeszkód w przepływie krwi w tętnicach
szyjnych i proksymalnych odcinkach tętnic przednich móz-gu, w ostrej fazie niedokrwiennego udaru mózmóz-gu, waha-nia ciśniewaha-nia tętniczego nie wywołują istotnych zaburzeń krążenia w wymienionych tętnicach śródczaszkowych, ocenianych metodą TCD.
H a s ł a: przezczaszkowa ultrasonografi a dopplerowska – tętnica przednia mózgu – udar niedokrwienny mózgu – nadciśnienie tętnicze.
Summary
Introduction: The current project was aimed at eluci-dating whether blood pressure fl uctuations in hyperten-sive patients with ischemic stroke, not characterized by hemodynamically signifi cant stenosis in carotid arteries and proximal segments of intracranial arteries lead to circulation disturbances in anterior cerebral arteries (ACAs) as visual-ized by transcranial Doppler ultrasound (TCD).
Material and methods: Sixty two hypertensive patients with the fi rst ever ischemic stroke were included in the study with the average age of 65.16 ± 11.52 years. Systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure values were analyzed. The following parameters were calculated based
CIRCULATION MONITORING IN ANTERIOR CEREBRAL ARTERIES IN HYPERTENSIVE PATIENTS 35 on the obtained blood fl ow velocity spectra: mean velocity
(Vmean), pulsatility index (PI) and resistance index (RI).
Results: A signifi cant decrease of SBP, DBP and MBP occurred between the fi rst and second day of observation, and no correlation between a reduction in arterial pressure and ACAs blood fl ow parameters was observed.
Conclusions: In hypertensive patients with ischemic stroke, not characterized by hemodynamically signifi cant stenosis within carotid arteries and proximal segments of anterior cerebral arteries, fl uctuations of arterial blood pres-sure do not cause substantial disturbances of circulation in the ACAs, as visualized by TCD.
K e y w o r d s: transcranial Doppler – anterior cerebral artery – ischemic stroke – blood hyperten-sion.
Introduction
Regardless of ongoing progress towards an understand-ing of cerebrovascular diseases and their underlyunderstand-ing causes, strokes still constitute one of the most crucial problems in medicine. It is due to their rate, resulting mortality, severe disability in motor control, which affects 70% of patients, as well as speech, and frequently, intellectual impairments which often persist [1, 2].
Hypertension is the most signifi cant risk factor of both ischemic and hemorrhagic stroke. Although advances have been made, the percentage of patients with properly con-trolled hypertension (systolic blood pressure – SBP < 140 mmHg and diastolic blood pressure – DBP < 90 mmHg) is below 50%, and 30% of people examined are unaware that they suffer from hypertension [3]. Hypertension aug-ments atherosclerosis, leading to macroangiopathy, such as coronary heart disease, myocardial infarction, peripheral arterial disease, stenosis or occlusion of extracranial arter-ies – especially the internal carotid artery, and the circle of Willis. It should be emphasized that SBP and DBP alone, as well as the combination of the two components, are important and independent stroke risk factors [4, 5]. In general, there is a continuous, linear correlation between the magnitude of hypertension, especially related to SBP, and the risk of stroke [3, 6]. An SBP elevation of 7.5 mmHg even within the range of 140–160 mmHg is associated with a twofold increase in the risk of a stroke. An mean blood pressure (MBP) elevation of 10 mmHg typically causes an increase in the risk of a stroke by 30% [6]. It is assumed that up to 40% of stroke cases occur even when SBP values slightly exceed 140 mmHg [5]. As a result of a stroke, a spontaneous elevation of blood pressure in both normotensive and hypertensive patients occurs. A rapid and excessive drop in arterial blood pressure may lead to decreased regional blood fl ow and enlargement of the ischemic area in the potentially necrosis-salvageable pe-numbra area [7, 8, 9, 10].
The current project was aimed at elucidating whether blood pressure fl uctuations in hypertensive patients with ischemic stroke, not characterized by hemodynamically signifi cant stenosis in carotid arteries and proximal segments of intracranial arteries lead to circulation disturbances in anterior cerebral arteries (ACAs), as visualized by tran-scranial Doppler ultrasound (TCD).
Material and methods
Sixty two hypertensive patients (30 females and 32 males), aged 45–86 years, mean age of 65.2 years, were included in the study: 1) in the acute phase of the fi rst ever incidence of neuroradiologically confi rmed stroke, 2) in the fi rst day of stroke, 3) with ischemic symptoms derived from the anterior cerebral circulation region, 4) who did not have any hemodynamically signifi cant stenosis in the carotid arteries, as visualized by USG-Doppler tests, 5) with the regular ventricular activity, 6) with temporal bone windows with unobstructed passage on each side, 7) who had signals from both ACAs recorded on the fi rst day of stroke, 8) with normal blood morphology. Some patients suffered from diabetes mellitus (21.4%), dyslipidemia (35.7%) or ischemic heart disease (30.3%).
Arterial blood pressure was measured with cardiomoni-tors (Philips M3046A) and an automatic blood pressure monitor (A&D Medical UA-787). Systolic blood pressure and DBP were analyzed. Obtained data were used to cal-culate MBP according to the following formula: MBP = DBP + 1/3 (SBP - DBP) [11, 12, 13, 14]. Measurements were performed on the limb unaffected by paresis or paralysis.
Blood pressure values used in the analysis were obtained immediately before each TCD test, the patient always re-mained in the horizontal position for 10 minutes prior to and during the measurement.
The Multi-Dop P apparatus and 2 MHz pulsatile head were employed in the study. The following parameters were calculated based on the obtained blood fl ow velocity spectra:
mean velocity (Vmean) based on the formula Vmean = (Vmax + [Vmin x 2]) / 3, Gosling pulsatility index (PI) based on the formula PI = (Vmax - Vmin) / Vmean and Pourcelot’s resist-ance index (RI) based on the formula RI = (Vmax - Vmin) / Vmax [15]. The baseline TCD test, preceded by the baseline arterial blood pressure measurement, was performed as soon as possible following the inclusion of the patient to study procedure. In the subsequent days, TCD was performed approximately at 10.00 am with the patient in the horizontal position at least 2 hours after a meal. The measurements were performed by the same person in the same manner. The left side, and then, the right side were examined, regardless of infarction site. Throughout the course of the study, patients were treated in accordance with their general, neurological and medical condition. They were also receiving antihy-pertensive agents as recommended by the 2002 European Stroke Initiative (EUSI) [9].
36 ADRIAN ŻYWICA, JAROSŁAW PODBIELSKI, PRZEMYSŁAW NOWACKI, KRZYSZTOF SAFRANOW
Ultrasonography examination of extracranial arteries was done in the fi rst days of hospitalization with the Esaote AU5 apparatus with the 7.5 MHz linear head. Stenosis of any of the arteries, if at all present, did not exceed 40% of the lumen diameter.
Computer tomography (CT) was performed in the fi rst day of hospitalization to exclude hemorrhagic stroke [6, 9, 16]. In some patients, CT scans did not show defi ned infarct region, however, based on the size of the hypodense area, it was assumed that stroke was related to the large vessel and it was not lacunar stroke. Strokes likely stemmed from large vessel atherosclerosis, according to TOAS [17], as they were area-specifi c, and patients with atrial fi brillation were excluded from the study.
Statistical analysis
Most of the continuous variables analyzed had a statis-tical distribution signifi cantly different from normal distri-bution (Shapiro–Wilk test), therefore nonparametric tests were utilized herein. To determine the statistical signifi -cance of differences between values of two patient groups, the U Mann–Whitney test was used. The signifi cance of parameter changes in time was evaluated with Friedman’s Anova (for more than 2 measurements) followed by Wilcoxon matched pairs test. Wilcoxon matched pairs test was used to compare the parameters of the stroke-affected versus unaffected side. Correlation power between the variables was determined by Spearman’s rank correlation coeffi cient.
Values were considered signifi cantly different when p < 0.05.
Calculations were done with Statistica 7.1 Software.
Results
As shown in fi gure 1, a signifi cant 12 mmHg decrease in SBP values occurred between the fi rst and second day of hospitalization (p < 0.01). However, there was no correla-tion between SBP in the acute phase of the stroke studied and the anterior cerebral arteries (ACAs) fl ow parameters in the stroke-affected hemisphere and the unaffected one, as evidenced by the Vmean values (r = -0.14; p = 0.33 and r = -0.22; p = 0.12), PI (r = -0.03; p = 0.80 and r = 0.23;
p = 0.11) and RI (r = -0.03; p = 0.84 and r = 0.21; p = 0.15) – fi gure 2.
There was also no correlation between DBP in the stroke period studied and Vmean in both ACAs (r = -0.02; p = 0.8 and r = -0.04; p = 0.8). A weak positive correlation was noted between the DBP decrease in the fi rst 2 days and the decrease of PI and RI of the ACAs in the stroke-affected hemisphere:
PI (r = 0.33; p = 0.04) and RI (r = 0.31; p = 0.04).
In addition, a weak positive correlation was found be-tween the MBP values and the PI and RI resistance indices of the ACAs in the stroke-affected hemisphere (r = 0.29;
p = 0.03 and r = 0.30; p = 0.02). No correlation between MBP and Vmean in both ACAs was observed (r = -0.10; p
= 0.5 and r = -0.10; p = 0.5) – fi gure 2.
SBP – systolic blood pressure / skurczowe ciśnienie tętnicze; DBP – diastolic blood pressure / rozkurczowe ciśnienie tętnicze; MBP – mean blood pressure
/ średnie ciśnienie tętnicze
Fig. 1. The comparison of arterial blood pressure values in the subsequent days of stroke
Ryc. 1. Porównanie wartości ciśnienia tętniczego w kolejnych dobach udaru
Discussion
Numerous publications have described the infl uence of arterial blood pressure changes on cerebral blood fl ow, especially as related to the anterior portion of the system;
however, relationships defi ned in those papers show great discrepancies. In our study, the most signifi cant decrease of both SBP and DBP, and indirectly MBP, could be
ob-CIRCULATION MONITORING IN ANTERIOR CEREBRAL ARTERIES IN HYPERTENSIVE PATIENTS 37 of blood circulation in ACAs plays a crucial role in com-pensating for circulation defi ciencies in the area supplied by the interior carotid arteries, limiting the ischemic zone in the MCA. The results of our study indicate that ACAs circulation remains unimpaired in hypertensive patients regardless of blood pressure fl uctuations in the fi rst stage of ischemic stroke. Our study suggests that the lack of he-modynamically signifi cant stenoses in extracranial arteries or main trunks of ACAs “protects” stroke sufferers from the hemodynamic impairment of cerebral circulation in the basin of ACAs, when arterial blood pressure fl uctu-ates, and particularly, when it drops. Nazir et al. studied a similar group of patients, and these authors did not note a negative effect of signifi cantly decreased arterial blood pressure on blood fl ow velocity parameters in the USG Doppler internal carotid artery tests or in the TCD test [19]. Dyker et al. also reported that arterial blood pressure could be lowered pharmacologically in a safe manner by up to 10% between the second and seventh day of ischemic stroke without any negative effect on – as evidenced by TCD – cerebral circulation, however only in patients not exhibiting signifi cant stenoses in the carotid arteries [20].
Naritomi et al. used the Spect test and found that, by reduc-ing arterial blood pressure in stroke patients not display-ing any hemodynamically signifi cant stenoses, they saw a bilateral increase in cerebral blood fl ow [21].
Conclusions
In hypertensive patients with ischemic stroke, not char-acterized by hemodynamically signifi cant stenosis in carotid arteries and proximal segments of anterior cerebral arteries, fl uctuations of arterial blood pressure do not cause substan-tial disturbances of circulation in the ACAs, as visualized by transcranial Doppler ultrasound.
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Fig. 2. The comparison of mean velocity (Vmean), pulsatility index (PI) and resistance index (RI) of both anterior cerebral arteries (ACAs) in subsequent
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Ryc. 2. Porównanie wartości prędkości średniej (Vmean), wskaźnika pulsacji (PI) oraz wskaźnika oporu (RI) obu tętnic przednich mózgu (ACAs) w kolejnych
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