The use of succinates for the correction of metabolic disorders in the penumbra in patients with stroke

Author:
M.M. ODINAK, S.N. YANISHEVSKII, N.V. TSYGAN, S.YU. GOLOKHVASTOV, I.A. VOZNIUK, A.G. TRUFANOV.
Kirov Military Medical Academy, St. Petersburg.

Summary:
The aim of the study was to determine the quantitative content and correlation between metabolites in the core ischemic zone, the ischemic penumbra and the intact tissue of the opposite hemisphere in the acute stage of ischemic stroke using MR-spectroscopy. We studied 72 patients, including 37 patients (the main group) treated with the antioxidant mexidol (2-ethyl-6-methyl-3-hydroxypiridine succinate) in addition to standard therapy and 35 patients who received standard therapy only. The severity of stroke was assessed using the NIHSS. The Barthel index and Rankin scale were used to evaluate functional outcome in the 30th day, hydrogen MR-spectroscopy was used twice: in the first 24 h from disease onset and in the 5th day. Mexidol used in dose 500 mg intravenously during 14 days reduced significantly the content of lactate (p=0.002) and inositol (p=0.005) in the cells compared to the control group that enhanced the restoration of the balance between aerobic and anaerobic mechanisms of oxidation and positively influenced on the rehabilitation of patients. Positive correlations between the content of lactate in the ischemic penumbra and NIHSS scores (r=0.5786; p=0.049) and the negative correlation between the content of lactate in the ischemic penumbra and the degree of functional restoration assessed by the Barthel index (r= –0.6305; p=0.028) were found. These findings support the evidence for the interaction between the disturbance of glucose metabolism in conditions of hypoxia and the degree of nervous tissue damage.

Keywords: ischemic stroke, magnetic resonance spectroscopy, antioxidants, mexidol (2-ethyl-6-methyl-3-hydroxypiridine succinate).


Efficacy of mexidol in the combination with thrombolytic therapy in patients with ischemic stroke

Author:
Zh.Yu. CHEFRANOVA, T.A. MAKOTROVA, V.A. UDACHIN, E.V. KOLEDINTSEVA

Summary:
Comparative efficiency of ethylmethylhydroxypyridine succinate (Mexidol) in combination with thrombolytic therapy in patients with ischemic stroke was studied in 116 patients. All patients divided into 2 groups: group (46 patients) received thrombolysis with mexidol and group (70 patients) received thrombolysis with standard therapy. These results showed that the synergy this one therapy leads to significantly faster normalize acute indicators, which correlated with the degree of reduction the neurological deficiency. Thus, the results showed that the synergistic therapy creates the conditions not only for the restoration of neurological status, but also to prevent secondary brain damage.

Keywords: ischemic stroke, mexidol (ethylmethylhydroxypyridine succinate), combination with thrombolytic therapy.


Changes in the hemostasis system and free-radical lipid oxidation in the acute stage of ischemic stroke in patients on neuroprotection treatment

Author:
G.I. IZHBULDINA

Summary:
We examined 163 patients with primary ischemic stroke admitted within the first 12 h after stroke onset. Neurological status on the Orgogozo scale and blood test results (lipid spectrum, level of free-radical lipid oxidation measured with chemiluminescent method, hemostasis system parameters) were estimated at admission and on the 21th day of stroke. Patients were stratified into 3 groups: group 1 (n=59) received traditional treatment and mexidol during the first 10 days in dose 500,0 mg intravenously and cerebrolysate in dose 1,0 ml intramuscular; group 2 (n=60) received cerebrolysate in dose 1,0 ml intramuscular during 10 days in addition to traditional treatment; group 3 (n=44) received only traditional treatment. At baseline, patients with ischemic stroke demonstrated the increase in blood plasma atherogenicity (p<0,05), intensity of free-radical lipid oxidation and thrombogenic potential of blood that were correlated with disease severity. Administration of neuroprotective drugs mexidol and cerebrolysate in addition to complex treatment of stroke improved the lipid spectrum, reduced the intensity of free-radical lipid oxidation, stabilized hemostasis parameters. The increase in survival rate and more rapid reversal of neurological deficit in patients of group 1 were identified to the 21th day.

Keywords: ischemic stroke, lipid spectrum, free-radical process, hemostasis, neuroprotective therapy, mexidol, cerebrolysate.


The randomized double-blind placebo-controlled study of efficacy and safety of mexidol in the complex therapy of ischemic stroke in the acute period

Author:
V.I. SKVORTSOVA, L.V. STAKHOVSKAYA, YA.R. NARTSYSSOV, M.K. BODYKHOV, I.V. KICHUCK, YU.V. GUDKOVA, T.D. SOLDATENKOVA, T.T. KONDRASHEVA, E.V. KALININA, M.D. NOVICHKOVA, O.B. KERBIKOV.

Summary:
The first randomized double-blind placebo-controlled study of efficacy of mexidol has been conducted. Fifty-one patients with ischemic stroke, aged 45-85 years, admitted during the first 24 hours after stroke were switched to mexidol in dosage 300 mg daily during 14 days. Twenty seven patients received the placebo using the same scheme. The significant forward dynamics in regress of neurological disturbances on the NIH scale was found to the 14th day in patients treated with mexidol as compared to the placebo group (p<0.05), along with functional rehabilitation assessed according to the dynamics of clinical scores on the Bartel scale to the 21st day after stroke (p<0.05) in patients involved in the study during the first 6 hours after disease onset. The normalization of functional brain activity was revealed in patients receiving mexidol, in comparison with the placebo, i.e. during the acute pharmacological test. A study of the antioxidant system demonstrated the increase of enzyme activity (superoxide dismutase, glutathione peroxidase, glutathione reductase) and the analysis of enzyme activity of the respiratory mitochondrial chain revealed the increase of succinate dehydrogenase activity in patients receiving mexidol. The results confirm the clinical efficacy of mexidol in the acute period of ischemic stroke in the carotid system of atherothrombotic or cardioembolic pathogenetic types, especially for its earlier (up to 6 hours) prescription, and specify mechanisms of its action (antihypoxic, antioxidant) in clinical conditions.

Keywords: ischemic stroke, mexidol.