Effects of nimodipine combined with betahistine on CRP and other inflammatory cytokines and vascular endothelial function in patients with hypertensive cerebral vasospasm

Abstract

OBJECTIVE:

This study aims to investigate the effect of nimodipine combined with betahistine on the levels of CRP and other inflammatory cytokines, as well as vascular endothelial function in patients with hypertensive cerebral vasospasm.

METHODS:

A total of 80 patients with hypertensive cerebral vasospasm from March 2016 to September 2018 were enrolled and randomly equally divided into two groups. At 1 week before enrollment, the application of all antihypertensive drugs was stopped. Then amlodipine tablets were used in control group, based on which nimodipine tablets were applied in observation group. All the patients included were followed up for 1 month. The changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were measured and compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared, while the adverse reactions and the overall clinical treatment effect of the two groups were evaluated.

RESULTS:

The cerebral vasospasm indexes in observation group were significantly lower than those in control group at 3 d, 1 week and 1 month after treatment (p < 0.05). At 1 month after treatment, the levels of inflammatory cytokines such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in observation group were significantly reduced compared to those in control group (p < 0.05). As for vascular endothelial function-related indicators, the endothelin-1 (ET-1) level in observation group was markedly lower than that in control group, whereas the level of nitric oxide (NO) was statistically higher than that in control group (p < 0.05). The cerebral vasospasm index was statistically positively correlated with changes in hs-CRP, IL-6, TNF-α and ET-1 (p < 0.05), but negatively correlated with changes in NO (p < 0.05). Besides, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were significantly higher than those in control group (p < 0.05). The overall treatment effective rate in observation group was markedly higher than that in control group (p < 0.05), and there were no significant differences of adverse reactions between the two groups (p > 0.05).

CONCLUSION:

For the treatment of hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body’s aseptic inflammatory responses, improve vascular endothelial function and increase the cerebral circulation blood flow, which offers a favorable strategy for clinical therapy.

Keywords

Betahistine hypertension cerebral vasospasm inflammatory cytokine vascular endothelial function nimodipine

1 Introduction

Essential hypertension can cause cerebral vascular hemodynamic disorder and cerebral vasospasm, often manifested as cerebral arterial spasm symptoms such as dizziness and headache due to insufficient blood supply to the brain. It even gives rise to cerebral arteriosclerosis and stroke with the prolongation of the course of the disease [1]. The longtime of high level of blood pressure results in the damage of vascular wall [2], and decrease of cerebrovascular elasticity. The lipid deposition on the vascular wall occurs in the damaged part of cerebral vessels, and target organ of cerebral vessels was ultimately impaired owing to atherosclerosis, stenosis of the lumen of cerebral vessels, hemodynamic changes, increased blood flow rate and reduced blood flow [3]. It has been implicated that hypertension, diabetes and dyslipidemia are associated with cardiovascular diseases development [4]. Particularly, mild hypertension is related with the rise of platelets aggregability, moderate hypertension is accompanied by the reduction of red blood cells deformability and increase of erythrocyte aggregability [5]. Moreover, previous finding suggested that 93% of the patients with long-term essential arterial hypertension have microcirculatory disorders [6]. the microvascular rarefaction appears to be an early vascular structural alteration in the setting of hypertension [7]. It has been indicated that microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension [8].

Previous evidence indicated that the occurrence of LA was implicated with the increasing levels of inflammatory factors in the patients, aggregation of cognitive dysfunction and impairment vascular endothelial functions [9]. Nimodipine, as a calcium antagonist, is currently the first choice for the treatment of cerebral vasospasm, but it has many adverse reactions on account for long term use while the gradual decrease drug sensitivity also affects the actual clinical effect [10]. Nimodipine was shown to inhibit platelet aggregation [11, 12]. Betahistine is a new type of H1 receptor agonist, which can antagonize catecholamine vasoconstrictive effect and play a significant role in dilating blood vessels. It exerts remarkable function in increasing basilar artery blood flow and capillary permeability for cerebral vessels [13]. At the same time, it exhibits a certain effect to resist plasma coagulation and inhibit platelet aggregation, so as to improve cerebral hemodynamics [14] and ensure the balance between supply and demand of cerebral oxygen [15]. So far, it has been extensively used in the treatment of vertigo but rarely applied for the therapy of hypertensive cerebral vasospasm. In this study, nimodipine and betahistine were used in patients with hypertensive cerebral vasospasm, and their effects on inflammatory cytokines and vascular endothelial function were analyzed.

2 Materials and methods

2.1 General data

A total of 80 patients with hypertensive cerebral vasospasm admitted to ShenZhen DaPeng new district NanAo People’s Hospital from March 2016 to September 2018 were enrolled. All patients signed the informed consent before inclusion, and this study was reported to the Ethics Committee of the hospital for approval (NA2016012). The diagnosis was based on the clinical manifestation, previous medical history, transcranial Doppler ultrasound examinations of the head and neck, etc. Inclusion criteria: Patients who took no drugs to regulate blood pressure at 7 d before inclusion, those whose systolic pressure exceeded 140 mmHg and diastolic pressure exceeded 90 mmHg at the time of inclusion, those aged 50–70 and those whose education level was in primary school and above. Exclusion criteria: Patients with secondary hypertension, heart failure caused by various reasons, severe liver and kidney insufficiency, cerebrovascular malformation, a stroke history, allergy to drugs, mental illness, language dysfunction, immune system disease or systemic infection, or those receiving anesthesia at 3 months before inclusion. The patients were randomly equally divided into two groups. Observation group included 21 males and 19 females aged 51–70, with an average age of (64.1±1.2) years old. The course of hypertension of them was 10–33 years, with an average of (13.3±1.5) years. Among them, there were 19 former smokers, 11 former alcoholics, 21 cases complicated with diabetes, 17 cases complicated with hyperlipidemia and 17 cases complicated with chronic obstructive pulmonary disease. Control group consisted of 22 males and 18 females aged 50–69, with an average age of (64.2±1.3) years old. The course of hypertension of them was 10–34 years, with an average of (13.4±1.5) years. Among them, there were 18 former smokers, 12 former alcoholics, 20 cases complicated with diabetes, 16 cases complicated with hyperlipidemia and 18 cases complicated with chronic obstructive pulmonary disease. There were no statistically significant differences in gender, age, the course of hypertension, histories of smoking and drinking and common medical diseases between the two groups (p > 0.05).

2.2 Methods

Patients in control group stopped all intravenous and oral antihypertensive medication at 1 week before inclusion. They were examined by transcranial Doppler ultrasound for cerebral vessels and carotid arteries, and the relevant parameters were recorded to calculate the cerebral vasospasm index as previously described [16]. As for the use of antihypertensive drugs, amlodipine tablets were given at 5 mg/d, and according to the condition of blood pressure regulation, the dosage should be appropriately increased until it reached 10 mg/d. Meanwhile, nimodipine tablets (Guangdong Huanan Pharmaceutical Group Co., Ltd., NMPN: 440225019) were taken for 3 times a day, with 30 mg each. Based on the treatment in control group, betahistine mesylate tablets (Eisai China Inc., NMPN:H20040130) were provided after meals for 3 times a day, with 6 mg each in observation group, and they were continuously taken for 1 month (a course of treatment) in both groups.

2.3 Observation indicators

All patients included were followed up for 1 month. Changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared between the two groups. The adverse reactions and the overall clinical treatment effective rate of the two groups were evaluated.

2.4 Evaluation criteria

The Doppler Box T-type color Doppler diagnostic apparatus (DWL, Germany) was applied for detection, in which the detection depth of the bilateral middle cerebral artery blood flow velocity was 50–60 mm, and the detection depth of the vertebral artery was 45–55 mm. The blood flow velocity of the internal carotid artery was based on the extracranial segment. Cerebral blood flow = internal carotid artery blood flow+vertebral artery blood flow. Cerebrovascular spasm index = bilateral middle cerebral artery blood flow velocity / average blood flow velocity in the extracranial segment of the internal carotid artery (normal value = 1.3–2.1) [17]. Patients with cerebrovascular spasm index≥3 can be definitely diagnosed with cerebral vasospasm. Cerebrovascular spasm index≥6 indicates severe cerebral vasospasm, and 2.1–3.0 indicates increased cerebral blood flow velocity. The therapeutic effect of cerebral vasospasm: marked effective: the cerebral vasospasm index returned to normal, effective: the cerebral vasospasm index returned to 2.1–3.0, and ineffective: the cerebral vasospasm index did not change or even increased after treatment. Clinical effect evaluation: markedly effective: diastolic blood pressure was decreased by more than 20 mmHg or by more than 10 mmHg but less than 90 mmHg after treatment, or transcranial Doppler detection showed the cerebral blood flow velocity≤120 cm/s; effective: diastolic blood pressure was decreased by 10–20 mmHg or by more than 10 mmHg but less than 90 mmHg, systolic blood pressure was decreased by more than 30 mmHg after treatment, or transcranial Doppler detection revealed that the brain blood velocity was 120 cm/s–160 cm/s; and ineffective: diastolic blood pressure dropped within 10 mmHg or by more than 90 mmHg after treatment, or transcranial Doppler detection manifested that the brain blood velocity was≥160 cm/s. Inflammatory cytokines: high-sensitivity C-reactive protein (hs-CRP, normal reference value in adults:<10 mg/L), interleukin-6 (IL-6, normal reference value in adults: 0.37–0.46 ηg/L) and tumor necrosis factor-α (TNF-α, normal reference value in adults: 5–100 ηg/L) based on previous data [18, 19]. Vascular endothelial function-related indicators: vascular endothelin-1 (ET-1, normal reference value in adults: 43.50–58.38 ηg/L) and nitric oxide (NO, normal reference value in adults: 13.8–34.6 μ mol/L) [20, 21].

2.5 Statistical processing

SPSS20.0 was adopted for statistical processing. Measurement data were expressed as mean±standard deviation (‘χ±s). The comparison of the mean between the two groups was detected via the t test, and the comparison of the rate between the two groups was examined via the χ² test. p < 0.05 indicated that the difference was statistically significant.

3 Results

3.1 Changes in the cerebral vasospasm indexes in the two groups during treatment

Before treatment and at 3 d, 1 week and 1 month after treatment, the cerebral vasospasm indexes were (6.5±0.4), (4.1±0.3), (2.5±0.2) and (1.7±0.1), respectively in observation group and (6.6±0.4), (5.5±0.4), (4.6±0.3) and (3.3±0.2), respectively in control group. It was found that the cerebral vasospasm indexes at 3 d, 1 week and 1 month after treatment in observation group were significantly lower than those in control group (t = 17.709, 36.836 and 45.255, p < 0.05) (Fig. 1).

Fig.1

Changes in the cerebral vasospasm indexes in the two groups at different time after treatment.

3.2 Comparisons of inflammatory cytokines and vascular endothelial function-related indicators between the two groups

At 1 month after treatment, the levels of inflammatory cytokines such as hs-CRP, IL-6 and TNF-α in observation group were significantly decreased those in control group (p < 0.05). As for vascular endothelial function-related indicators, the ET-1 level in observation group was markedly lower than that in control group, while the NO level was higher than that in control group (p < 0.05) (Table 1).

Table 1
Comparisons of inflammatory cytokines and vascular endothelial function-related indicators between the two groups ( $\bar{χ} \pm s$ )

hs-CRP (mg/L) IL-6 (ηg/L) TNF-α (ηg/L) ET-1 (ηg/L) NO (μ mol/L)

Observation group 4.4±0.2 0.4±0.1 67.3±4.3 52.1±3.1 55.1±7.3

Control group 13.2±1.4 1.2±0.1 124.3±8.8 78.8±8.0 31.2±1.3

χ ² 39.355 35.777 36.807 19.682 20.386

P 0.000 0.000 0.000 0.000 0.000

	hs-CRP (mg/L)	IL-6 (ηg/L)	TNF-α (ηg/L)	ET-1 (ηg/L)	NO (μ mol/L)
Observation group	4.4±0.2	0.4±0.1	67.3±4.3	52.1±3.1	55.1±7.3
Control group	13.2±1.4	1.2±0.1	124.3±8.8	78.8±8.0	31.2±1.3
χ ²	39.355	35.777	36.807	19.682	20.386
P	0.000	0.000	0.000	0.000	0.000

3.3 Correlation analysis of the cerebral vasospasm index with changes in inflammatory cytokines

Our data revealed that the cerebral vasospasm index was positively correlated with changes in hs-CRP, IL-6 and TNF-α (p < 0.05) (Figs. 2–4).

Fig.2

Correlation analysis of the cerebral vasospasm index with changes in the hs-CRP level.

Fig.3

Correlation analysis of the cerebral vasospasm index with changes in the IL-6 level.

Fig.4

Correlation analysis of the cerebral vasospasm index with changes in the TNF-α level.

3.4 Correlation analysis of the cerebral vasospasm index with changes in vascular endothelial function-related indicators

We also found that there was a positive correlation between the cerebral vasospasm index and ET-1 changes (p < 0.05) and a negative correlation between the cerebral vasospasm index and NO changes (p < 0.05) (Figs. 5, 6).

Fig.5

Correlation analysis of the cerebral vasospasm index with changes in the ET-1 level.

Fig.6

Correlation analysis of the cerebral vasospasm index with changes in the NO level.

3.5 Comparisons of effective rates of blood pressure regulation and cerebral vasospasm treatment between the two groups

After 1-month follow-up, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were remarkably higher than those in control group (p < 0.05) (Table 2).

Table 2
Comparisons of effective rates of blood pressure regulation and cerebral vasospasm treatment between the two groups [n (%)]

Effective rate of blood pressure regulation Effective rate of cerebral vasospasm treatment

Observation group 37 (92.5%) 39 (97.5%)

Control group 21 (52.5%) 23 (57.5%)

χ ² 14.107 12.037

p 0.000 0.001

	Effective rate of blood pressure regulation	Effective rate of cerebral vasospasm treatment
Observation group	37 (92.5%)	39 (97.5%)
Control group	21 (52.5%)	23 (57.5%)
χ ²	14.107	12.037
p	0.000	0.001

3.6 Comparison of the overall treatment effective rate between the two groups

The overall treatment effective rate in observation group (92.5%) was evidently higher than that in control group (57.5%) (χ² = 11.267, p = 0.001 < 0.05) (Table 3).

Table 3
Comparison of overall treatment effective rate between the two groups [n (%)]

Marked effective Effective Ineffective

Observation group 24 13 3

Control group 10 13 17

	Marked effective	Effective	Ineffective
Observation group	24	13	3
Control group	10	13	17

3.7 Comparisons of adverse reactions occurred during treatment between the two groups

There was no statistically significant difference in the total incidence rate of adverse reactions such as nausea, vomiting, rash, hypotension and flushed face between the two groups (p > 0.05) (Table 4).

Table 4
Comparisons of adverse reactions occurred during treatment between the two group [n (%)]

Nausea and vomiting Rash Hypotension Flushed face Total incidence rate

Observation group 2 3 2 1 8 (20.0%)

Control group 2 1 2 2 7 (17.5%)

χ ² – 0.082

p – 0.775

	Nausea and vomiting	Rash	Hypotension	Flushed face	Total incidence rate
Observation group	2	3	2	1	8 (20.0%)
Control group	2	1	2	2	7 (17.5%)
χ ²	–				0.082
p	–				0.775

4 Discussion

As the course of hypertension extended, dysfunction occurs the arterial blood circulation system, in which systolic blood pressure or (and) diastolic blood pressure may be significantly increased [22]. The induced atherosclerosis seriously affects the blood supply of various organs, especially important organs such as the heart, brain and kidney, and tissues of the body, which interfered the quality of life of patients [23]. Vessel diameters were subject to complex regulation involving morphometric characteristics, sex, wall thickness, hypertension, LDL cholesterol levels, and alcohol consumption [24]. Generally, in the early stage of hypertension, apparent lesions emerged in the intracranial arterial blood vessels, and arteriospasm represents the most common clinical manifestation. Gradually, intracranial cerebral arteries extensively harden, and then the cerebral blood supply becomes insufficient [25]. At present, the most effective examination method for cerebral arterial spasm is transcranial Doppler ultrasound examination, which judges cerebral vasospasm through the measurement of the cerebral blood flow velocity. It has been ubiquitously utilized for diagnosis and to assist for intervention in the early stage. For instance, it guides the antihypertensive and spasmolytic treatment to better ensure the cerebral arterial blood flow and improve the cerebral oxygen supply [26].

In this study, we determined the role of betahistine, based on the nimodipine, for therapy of hypertensive cerebral vasospasm. It was found that the cerebral vasospasm indexes at 3 d, 1 week and 1 month after betahistine+nimodipine treatment were significantly improved compared to the single use of nimodipine. According to the comparative analysis of inflammatory cytokines and vascular endothelial function-related indicators between the two groups after treatment, we found the combination use of two medicines can markedly reduce the levels of hs-CRP, IL-6, TNF-α and ET-1 compared to the single use of nimodipine, with elevation of NO level, indicating that vascular endothelial function was improved. In addition, the correlation analysis of the cerebral vasospasm index with changes in vascular endothelial function-related indicators demonstrated that there was a positive correlation between the cerebral vasospasm index and ET-1 value and a negative correlation between the cerebral vasospasm index and NO level. The above results indicate that after the treatment of patients with hypertensive cerebral vasospasm with betahistine tablets, the level of inflammatory cytokines in the body is decreased with the improvement of cerebral vasospasm, and the vascular endothelial function also changes with the improvement of cerebral vasospasm. At the same time, after follow-up for 1 month, it was found that the combined use of betahistine and nimodipine remarkably increased the effective rate of blood pressure regulation and the overall treatment effective, further suggesting that the combination therapy for hypertensive cerebral vasospasm has positive significance in relieving cerebral vasospasm and improving the overall clinical effect. Finally, the adverse reactions were also evaluated and no statistical differences of nausea, vomiting, rash, hypotension and flushed face between the two groups were found, indicating that the inevitable safety of betahistine, along with nimodipine.

The betahistine tablets used in observation group in this study were H1 receptor agonists, which have obvious antihistamine effects and can dilate blood vessels [27], especially vertebral-basilar arteries in cerebral vessels. It is therefore often used in the treatment of vertigo [28]. After oral administration, the betahistine tablets can increase the cerebrovascular blood flow, improve cerebral circulation [29] and alleviate aseptic inflammatory responses in the body. At the same time, they also exert certain effects on inhibiting platelet chemotaxis and aggregation [30] and have great significance in reducing platelet adhesion and increasing the permeability of vascular endothelial cells to red blood cells [31]. Besides, they protect vascular endothelial cell function, reduce the blood viscosity, increase the cerebral circulation blood flow [32] and reduce water content in brain cells. They present essential values for improving brain cell edema caused by cerebral artery spasm during hypertension. Through directly acting on cerebral vascular smooth muscles, it facilitates cerebral vasodilation, reduces cerebral circulation resistance, accelerates cerebral circulation and increases the cerebral oxygen supply [33 –35].

5 Conclusion

In conclusion, for hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body’s aseptic inflammatory responses, improve vascular endothelial function, increase the cerebral circulation blood flow and achieve the purpose of improving cerebral circulation, which provides promising clinical value for the therapy.

Conflict of interest

None.

References

Chen

, Hung

, Wu

, Lin

, TAIPAI study group. Primary Aldosteronism and Cerebrovascular Diseases. Endocrinol Metab (Seoul). 2018;33(4):429–34.

Chen

, Li

, Zhang

, Hu

, Li

, Feng

, Yao

, Zhang

, et al. Alleviation of mechanical allodynia by 14,15-EET in a central post-stroke pain model: possible role of allopregnanolone and δGABAAR. J Pain. 2018;27(11):526–9.

Lorusso

, Folliguet

, Shrestha

, Meuris

, Kappetein

, Roselli

, et al. Sutureless versus Stented Bioprostheses for Aortic Valve Replacement: The Randomized PERSIST-AVR Study Design. Thorac Cardiovasc Surg. 2018;29(10):55–8.

Sepulveda

, Palomo

, Fuentes

. Antiplatelet activity of drugs used in hypertension, dyslipidemia and diabetes: Additional benefit in cardiovascular diseases prevention. Vascul Pharmacol. 2017;91:10–7.

Konstantinova

, Ivanova

, Tolstaya

, Mironova

. Rheological properties of blood and parameters of platelets aggregation in arterial hypertension. Clin Hemorheol Microcirc. 2006;35(1-2):135–8.

Jung

, Kolepke

, Spitzer

, Kiesewetter

, Ruprecht

, Bach

, et al. Primary and secondary microcirculatory disorders in essential hypertension. Clin Investig. 1993;71(2):132–8.

de Moraes

, Tibirica

. Early Functional and Structural Microvascular Changes in Hypertension Related to Aging. Curr Hypertens Rev. 2017;13(1):24–32.

Jung

, Pindur

, Ohlmann

, Spitzer

, Sternitzky

, Franke

, et al. Microcirculation in hypertensive patients. Biorheology. 2013;50(5-6):241–55.

Lin

, Zhang

, Zeng

, Lin

, Geng

, Wang

. Atherosclerosis, inflammatory factor changes, cognitive disorder and vascular endothelial functions in patients with different grades of leukoaraiosis. Clin Hemorheol Microcirc. 2019;73(4):591–7.

10.

Hooper

, Al-Khudairy

, Abdelhamid

, Rees

, Brainard

, Brown

, et al. Omega-6 fats for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;29(11):94–100.

11.

Lopez

, Redondo

, Salido

, Pariente

, Rosado

. Two distinct Ca2+compartments show differential sensitivity to thrombin, ADP and vasopressin in human platelets. Cell Signal. 2006;18(3):373–81.

12.

Feinberg

, Bruck

. Effect of oral nimodipine on platelet function. Stroke. 1993;24(1):10–3.

13.

Abdelhamid

, Martin

, Bridges

, Brainard

, Wang

, Brown

, et al. Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;27(11):45–9.

14.

Morris

, Chen

, Laskar

, Smith

, Vega

. Mortality in status 2 patients listed for heart transplantation in the United States: Will understanding cause of death help justify implantation of left ventricular assist devices into less sick patients? Int J Cardiol. 2018;9(9):167–77.

15.

Thingstad

, Askim

, Beyer

, Bråthen

, Ellekjær

, Ihle-Hansen

, et al. The Norwegian Cognitive impairment after stroke study (Nor-COAST): study protocol of a multicentre, prospective cohort study. BMC Neurol. 2018;18(1):193.

16.

Dietrich

, van Lieshout

, Fischer

, Kamp

, Cornelius

, Tortora

, et al. Transcranial Doppler Ultrasound, Perfusion Computerized Tomography, and Cerebral Angiography Identify Different Pathological Entities and Supplement Each Other in the Diagnosis of Delayed Cerebral Ischemia. Acta Neurochir Suppl. 2020;127:155–60.

17.

Aaslid

. Hemodynamics of cerebrovascular spasm. Acta Neurochir Suppl. 1999;72:47–57.

18.

Barbaro

, Fontana

, Modolo

, De Faria

, Sabbatini

, Fonseca

, et al. Increased arterial stiffness in resistant hypertension is associated with inflammatory biomarkers. Blood Press. 2015;24(1):7–13.

19.

, Jiang

, Lu

, Shi

. Chemerin is associated with inflammatory markers and metabolic syndrome phenotypes in hypertension patients. Clin Exp Hypertens. 2014;36(5):326–32.

20.

, Zhang

, Zhao

, Chen

, Liu

. Chinese herbal medicine bushen qinggan formula for blood pressure variability and endothelial injury in hypertensive patients: a randomized controlled pilot clinical trial. Evid Based Complement Alternat Med. 2014;2014:804171.

21.

Saji

. Clinical characteristics of pulmonary arterial hypertension associated with Down syndrome. Pediatr Int. 2014;56(3):297–303.

22.

Rocha

, Tam

, Karkhanis

, Nedadur

, Fang

, Tu

, et al, Fremes

. Multiple Arterial Grafting Is Associated With Better Outcomes for Coronary Artery Bypass Grafting Patients. Circulation. 2018;138(19):2081–90.

23.

Yamaguchi

, Iwasaki

, Wada

, Makita

, Nagasawa

, Yamakawa

, et al. Transient Lesion of the Splenium of the Corpus Callosum after Acute Ischemic Stroke: A Report of Two Cases. Intern Med. 2018;9(10):169–81.

24.

Kiechl

, Willeit

. The natural course of atherosclerosis. Part II: vascular remodeling. Bruneck Study Group. Arterioscler Thromb Vasc Biol. 1999;19(6):1491–8.

25.

Bulluck

, Chan

, Bryant

, Chai

, Chawla

, Chua

, et al, Hausenloy

. Platelet Inhibition to Target Reperfusion Injury (The PITRI trial): Rationale and Study Design. Clin Cardiol. 2018;12(9):32–5.

26.

Becher

, Eder

, Baumann

, Loßnitzer

, Pollmann

, Behnes

, et al. Unprotected versus protected high-risk percutaneous coronary intervention with the Impella 2.5 in patients with multivessel disease and severely reduced left ventricular function. .Medicine (Baltimore). 2018;97(43):e12665.

27.

Marsman

, Özdemir-van Brunschot

DMD

, Jahrome

, Veeger

NJGM

, Schuiling

, van Rooij

, et al. Case Series about the Changed Antiplatelet Protocol for Carotid Endarterectomy in a Teaching Hospital: More Patients with Complications? Surg J (N Y). 2018;4(4):e220–5.

28.

Cannon

, McGuire

, Pratley

, Dagogo-Jack

, Mancuso

, Huyck

, et al. Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV). Am Heart J. 2018;206(5):11–23.

29.

Vakhitov

, Oksala

, Saarinen

, Vakhitov

, Salenius

, Suominen

. Survival of Patients and Treatment-Related Outcome After Intra-Arterial Thrombolysis for Acute Lower Limb Ischemia. Ann Vasc Surg. 2018;29(9):90–9.

30.

Al-Mufti

, Kamal

, Damodara

, Nuoman

, Gupta

, Alotaibi

, et al. Updates In The Management Of Cerebral Infarctions And Subarachnoid Hemorrhage Secondary To Intracranial Arterial Dissection: A Systematic Review. World Neurosurg. 2018;27(9):78–87.

31.

Abrich

, Narichania

, Love

, Lanza

, Shen

, Sorajja

. Left atrial appendage exclusion during mitral valve surgery and stroke in atrial fibrillation. J Interv Card Electrophysiol. 2018;28(9):107–8.

32.

Ursulescu

, Baumann

, Ferrer

, Contino

, Romagnoni

, Antona

, et al. Optilene, a new non-absorbable monofilament is safe and effective for CABG anastomosis. OPTICABG – A prospective international, multi-centric, cohort study. Ann Med Surg (Lond). 2018;15(35):13–9.

33.

Chung

, Yoon

, Lee

, Shin

, Kim

, Park

, et al. Medication Adherence of Statin Users after Acute Ischemic Stroke. Eur Neurol. 2018;80(1-2):106–14.

34.

Wang

, Li

, Zhang

, Dai

, Zuo

, Wang

, et al. Oxidized Low-Density Lipoprotein to High-Density Lipoprotein Ratio Predicts Recurrent Stroke in Minor Stroke or Transient Ischemic Attack. Stroke. 2018;49(11):2637–42.

35.

Zhu

, Liu

, Pan

, Jing

, Li

, Zhao

, et al. Elevated Neutrophil and Presence of Intracranial Artery Stenosis Increase the Risk of Recurrent Stroke. Stroke. 2018;49(10):2294–300.

Effects of nimodipine combined with betahistine on CRP and other inflammatory cytokines and vascular endothelial function in patients with hypertensive cerebral vasospasm

Abstract

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1 Introduction

2 Materials and methods

2.1 General data

2.2 Methods

2.3 Observation indicators

2.4 Evaluation criteria

2.5 Statistical processing

3 Results

3.1 Changes in the cerebral vasospasm indexes in the two groups during treatment

Table 3 Comparison of overall treatment effective rate between the two groups [n (%)] Marked effective Effective Ineffective Observation group 24 13 3 Control group 10 13 17

Table 4 Comparisons of adverse reactions occurred during treatment between the two group [n (%)] Nausea and vomiting Rash Hypotension Flushed face Total incidence rate Observation group 2 3 2 1 8 (20.0%) Control group 2 1 2 2 7 (17.5%) χ 2 – 0.082 p – 0.775

5 Conclusion

Conflict of interest

References

Table 3
Comparison of overall treatment effective rate between the two groups [n (%)]

Marked effective Effective Ineffective

Observation group 24 13 3

Control group 10 13 17

Table 4
Comparisons of adverse reactions occurred during treatment between the two group [n (%)]

Nausea and vomiting Rash Hypotension Flushed face Total incidence rate

Observation group 2 3 2 1 8 (20.0%)

Control group 2 1 2 2 7 (17.5%)

χ ² – 0.082

p – 0.775