Magnetic Resonance Imaging of Rat Brain in Assessment of the Neuroprotective Properties of Histochrome in Experimental Arterial Hypertension.

The neuroprotective effects of the course therapy with Histochrome in Wistar rats with modeled arterial hypertension were studied by using magnetic resonance imaging (MRI) in diffusion-weighted mode. The behavioral status of the animals was assessed using the open-field test. MRI analysis revealed more pronounced increase in the signaling characteristics of the brain tissue in hypertensive rats in comparison with the control (intact) animals. It was caused by excessive accumulation of fluid in the intra- and extracellular spaces of the brain tissue, which is associated with hypervolemia induced by the multifactorial cardiovasorenal model of hypertension. After a course of Histochrome injections to hypertensive rats, the cerebral microcirculation disorders were leveled, while the behavioral status was characterized by shortened latency of the visit to the center of the open field by 20% and improvement of cognitive activity (by 1.6 times) and the exploratory component (by 30%).

Magnetic Resonance Imaging in Assessment of Cardiac Remodeling in Rats with Experimental Arterial Hypertension.

Magnetic resonance imaging was employed to examine the morphofunctional status of myocardium in Wistar rats with multifactor cardiovasorenal model of arterial hypertension. In 3 months after the onset of experiment, the rats demonstrated a pronounced hypertrophy in left ventricular myocardium mostly due to thickening of the posterior and lateral walls against the background of relatively stable thickness of ventricular septum. The left ventricular endsystolic volume markedly increased in parallel with moderate increase of the end-diastolic volume. The standard calculated indices were used for precise assessment of the type of remodeling of individual myocardial structures. The study showed that multifactor arterial hypertension model was characterized by domination of hypertrophic mode of the left ventricular remodeling, whereas the concentric variant was observed more rarely by 2.5 times. The greatest alterations were observed in the posterior and lateral walls of the left ventricle, which could result from the hemodynamic effects of hypervolemic arterial hypertension.

Autonomic Cardiac Regulation in Experimental Comorbidity of Chronic Obstructive Pulmonary Disease and Acute Cerebral Ischemia.

Autonomic regulation of the heart was examined in 5 groups of rats: intact, sham-operated, experimental chronic obstructive pulmonary disease, acute cerebral ischemia, and acute cerebral ischemia modeled against the background of chronic obstructive pulmonary disease. The latter was provoked by combination of inhaled papain and intraperitoneal bacterial LPS, whereas acute cerebral ischemia was modeled by single-stage bilateral occlusion of the common carotid arteries. Chronic obstructive pulmonary disease was verified by X-ray computed microtomography. The disturbances in autonomic control of the heart during comorbid pathologies were most prominent; they were manifested by overstrain and decompensation of the mechanisms implicated in the heart control and systolic-diastolic arterial hypotension. The correlations were established between blood oxygenation, respiration rate, and some parameters of autonomic cardiac regulation. The data attest to relevance and usefulness of the developed model of respiratory and cerebrovascular comorbidity in assessment of pathophysiological mechanisms underlying dysregulation of the heart and the development of personalized approaches for its pharmacological correction.

Behavioral and Cognitive Reactions of Rats with Experimental Chronic Obstructive Lung Diseases of Different Degree.

The study presents the results of behavioral phenotyping of rats with experimental chronic obstructive pulmonary disease (eCOPD) of different severity modeled by using a combination of inductors (purified papain and bacterial LPS) in increasing concentrations. Locomotor and exploratory activity, spatial memory, and anxiety were evaluated. In mild eCOPD, locomotor and exploratory activity increased, while other parameters did not differ from the control values. Rats with moderate eCOPD demonstrated moderately restricted locomotor function and increased anxiety. Severe eCOPD was associated with pronounced changes in all analyzed parameters. Correlation analysis revealed relationships between some behavioral parameters and blood oxygen saturation, inspiratory lung volume, and respiration rate. This indicates the role of respiratory failure in the pathogenesis of cognitive disorders.

Assessment of Cardiac Vegetative Control during Acute Graduated Exogenous Normobaric Hypoxia in Rats.

The effects of exogenous normobaric hypoxic hypoxia on vegetative control of the heart and BP were examined in Wistar rats. The reference ranges of variation pulsometry parameters were determined in rats with normoxemia for 3 physiological variants of autonomic homeostasis: eutony, sympathicotony, and vagotony. Most rats (80%) demonstrated autonomic eutony. The study showed that saturation of arterial blood with oxygen is the most adequate assessment of severity of acute exogenous normobaric hypoxic hypoxia progressing within a closed hypoxic chamber, which standardizes this method and minimizes inaccuracies resulting from individual sensitivity to hypoxic stress. The changes in functional activity of systems that control the heart rhythm closely correlated with the drop in arterial blood oxygenation. While a small arterial hypoxemia activated the ergotropic elements of autonomic nervous system central subdivision accompanied by elevation of systolic BP, the moderate hypoxemia augmented the cholinergic influences and moderated the adrenergic ones under maintaining mobilization of the central autonomic nervous system-control loop and normotension. Severe hypoxemia was manifested by augmented influences from autonomic nervous system central subdivisions on the heart rate, disadaptation of the control systems, and systolic-diastolic arterial hypotension.

Evaluation of effects of histochrome and mexidol on structural and functional characteristics of the brain in senescence-accelerated OXYS rats by magnetic resonance imaging.

The effects of histochrome and mexidol on the morphology and function of the brain and behavior were studied in senescence-accelerated OXYS and Wistar rats. MRI showed that signs of neurodegenerative changes were present in OXYS rats at the age of 3 months and were pronounced at the age of 12 months. Histochrome (1 mg/kg, 5 days) more effectively than mexidol (4 mg/kg, 7 days) reduced anxiety and increased exploratory activity of 1-year-old OXYS rats. Both drugs improved the morphology and function of the brain. Their effects consisting in correction of diffuse changes in the white matter and reduction of edema were comparable; in addition, histochrome reduced the intensity of demyelinization processes.

[Characteristics of a vasomotor endothelial function of the major and cerebral arteries in bronchial asthma].

We investigated endothelium dependent and independent activity of major and cerebral arteries in mice with experimental bronchial asthma. Regional features of endothelium dependent reactions of arteries were established. It was found that the carotid artery has greater vasomotor activity than the medial cerebral artery. Development of experimental bronchial asthma is associated with sharp reduction of reserve ability for endothelium independent dilatation against intensification of endothelium dependent dilatation; enhancement of constrictor effects of vascular endothelium in major and attenuation in cerebral compartments.

[Interrelation of vasomotor effects in the endothelium of the cerebral and main arteries in obstructive pulmonary diseases].

We have investigated vasomotor activity of the trunk and cerebral arteries in mice with obstructive pulmonary diseases. It was established, that endothelial dysfunction depends on the form of pulmonary disease and has regional vascular features. It was determined, that the maximal disturbances are shown in mice with chronic obstructive pulmonary disease. It express as infringement of regional autonomy vasomotor effects and pathological paradoxical vasoconstriction of cerebral vessels. Bronchial asthma associates with the discordant answer of the brain and trunk arteries with the moderate adaptation of a regional homeostasis.

Peculiarities of vasomotor reaction of cerebral vessels in arterial hypertension.

We studied vasomotor activity of rat cerebral vessels. Peculiarities of endothelium-dependent reactions of cerebral arteries in induced arterial hypertension were revealed. Quantitative and qualitative relationships between the parameters of the vasomotor apparatus of cerebral arteries and parameters of circulatory homeostasis were determined.

Noninvasive study of vasodilatory activity of albino rat cerebral arteries.

Vasodilating activity of rat cerebral vessels was studied. Methodological peculiarities and chronotropic limits of vasomotor testing were determined. Qualitative and quantitative parameters of dilatation of vessels were determined and similarity of rat dilatation responses and human vasodilatory activity was described.

[Complex assessment of vasomotor function of vascular endothelium in patients with hypertension]. / Kompleksnaia otsenka vazomotornoi funktsii sosudistogo éndoteliia.

Vasomotor function of vascular endothelium was studied in 62 patients with grade 1-2 hypertension with moderate and high added risk. Methods included study of brachial and middle cerebral artery endothelium dependent and independent vasodilation/vasoconstriction, measurement of plasma levels of nitric oxide metabolites (NO(n)-), endothelin-1, and antithrombin, as well as registration of their changes during vasomotor tests with calculation of integral indexes. Most patients with hypertension differed from controls by preponderance of vasoconstrictor over vasodilator reactions both in peripheral and cerebral vascular bed. At the same time patients with hypertension had pronounced dissociation between vasomotor responses of cerebral and peripheral vessels compared with subjects with normal blood pressure (p<0.05). Besides lowered basal level of NO(n)- and high concentration of endothelin-1 patients with hypertension were characterized by hyperreactivity of nitricoxidergic system, augmented lability of endothelin producing system, and impaired athrombogenecity of vascular endothelium. Complex assessment of vasomotor function of vascular endothelium by sequential vasoactive tests characterizes functional and metabolic activity of cerebral and peripheral vessels and can be used for improvement of risk stratification and monitoring of efficacy of treatment of patients with hypertension.

[Arterial hypertension in menopausal women: Clinical, functional, and pharmaco-economical aspects]. / Kliniko-funktsional'nye i farmakoékonomicheskie aspekty arterial'noi gipertenzii u zhenshchin v klimaktericheskom periode.

The study was undertaken to define the specific features of daily variations of blood pressure (BP) and autonomic cardiac regulation (ACR), as well as the functional status of the myocardium and vascular endothelium in females with menopausal arterial hypertension (MPAH) and to assess the pharmacotherapeutic and economical aspects of the combined use of arifon retard and clinonorm. The study enrolled 30 reproductive females with mild and moderate arterial hypertension (AH) and 65 females with MPAH who were randomly divided into 2 groups according to the therapeutic model. MPAH was characterized by more unfavorable hemodynamic changes that AH in the presence of preserved fertile function: greater load on target organs, elevated BP, its inadequate nocturnal lowering, greater BP variations, the magnitude and rate of its morning elevation. In AH, the vasomotor function of the endothelium varies with the clinical form of the disease and with the functional status of the female reproductive system. By and large, in the group of patients with MPAH, the latter was characterized by a more significant decrease in endothelium-dependent vasodilation (EDVD). Arifon retard monotherapy has an adequate antihypertensive effect in female patients with MPAH, by ensuring 24-hour control of BP and affecting its chronostructure. A combination of arifon retard and climonorm has no cumulative effect on the level of BP and on the parameters of pressure-induced load; however, this is a pathogenetically grounded combination that potentiates the positive effects of a diuretic in significantly improving EDVD and ACR. The use of arifon retard in combination with climonorm in MPAH is the most cost-effective for public health care facilities and effective for patients. The course of MPAH is of certain peculiarity, which should be taken into account in choosing a therapeutic model for this category of patients.

[Dynamics of a 24-h profile of arterial pressure and function of the vascular endothelium in nebivolol treatment of hypertensive patients]. / Dinamika sutochnogo profilia arterial'nogo davleniia i funktsional'nogo sostoianiia sosudistogo éndoteliia pri lechenii nebivololom (nebilet) bol'nykh arterial'noi gipertenziei.

To assess a hypotensive activity of nebivolol (nebilet) including its action on the 24-h profile and baroreceptor control of arterial pressure (AP), vegetative regulation of the heart and vasculomotor endothelial function in AP patients, 30 AH patients were given nebivolol in a dose 5 mg/day for 8 weeks. The results of the treatment show that nebivolol effectively maintains a safe 24-h control of AP, acts positively on chronostructure of AP 24-h profile, produced no clinically significant side effects, corrects vegetative heart regulation and improves baroreceptor AP control. Moreover, nebilet modulates a stable vasodilating effect which improves function of vascular endothelium, initiates regression of left ventricular myocardium hypertrophy by raising its elasticity without changing much its contractile function. Thus, nebivolol is a highly effective drug for treatment of arterial hypertension which corrects a wide spectrum of unfavourable shifts in cardiovascular system function.

[Clinico-functional assessment of the daily dynamics of blood pressure in pneumonia patients]. / Kliniko-funktsional'naia otsenka sutochnoi dinamiki arterial'nogo davleniia u bol'nykh pnevmoniei.

AIM: To define the specific features of daily blood pressure (BP) variations in patients with extrahospital pneumonia (EHP) that has developed in the presence of baseline normotension and arterial hypertension (AH). MATERIAL AND METHODS: 83 patients aged 18 to 80 years who had EHP of varying severity were examined. Mild and moderate systolic and diastolic AH preceding EHP had occurred in 28 elderly patients. At the peak of the disease and before discharge, the patients underwent 24-hour BP monitoring with a portable ABPM-03 monitor ("Meditech", Hungary). RESULTS: At the peak of mild and moderate EHP, young patients had predominantly a normotensive daily BP curve whereas old patients with baseline normotension had systolic overload of target organs and a greater BP variability. At the peak of severe EHP, the normotensive patients had, irrespective of their age, systolic and diastolic arterial hypotension with a marked hypotensive overload and a low BP variability. In elderly patients with mild and moderate AH, non-severe EHP provoked negative changes in the daily BP profile (DBPP), which are indicative of an exacerbation of the disease as isolated systolic or systolic-and-diastolic AH, a greater BP variability, high values and rates of its morning elevation. At the peak of severe EHP, hypertensive old patients showed DBPP variations as two types: moderate systolic-and-diastolic hypotension or the unchanged hypertensive profile of a daily BP curve. CONCLUSION: Analyzing DBPP in patients with EHP has indicated that the nature and degree of its impairments at the peak of the disease are determined by three independent factors: age, severity of the disease, and baseline BP values. The findings may provide rational therapy for AH in patients with EHP.

[Baroreceptor regulation of arterial pressure in elderly patients with systolic and essential hypertension]. / Baroretseptornaia reguliatsiia arterial'nogo davleniia u lits pozhilogo vozrasta s izolirovannoi sistolicheskoi i sistolodiastolicheskoi arterial'noi gipertoniei.

AIM: To study efficiency of baroreceptor regulation of circulation with reference to vegetative regulation of the heart (VRH) and 24-h rhythms of blood pressure (BP) in elderly patients with systolic hypertension (SH) and essential hypertension (EH). MATERIAL AND METHODS: Synchronous 24-h monitoring of BP, ECG with evaluation of VRH by the system Cardio Tens 01 (Meditech, Hungary), examination of BP baroreceptor regulation from carotid areas with the method "cervical Camera" and in performing active orthostatic test were conducted in 50 elderly patients with mild and moderate SH and EH. RESULTS: Weakening of BP baroresponse was more noticeable in SH patients than in EH patients though the cardiochronotropic component of baroreflex in EH was stronger. Stimulation of the carotid baroreflex by elevated BP is accompanied by different weakening of adrenergic efferentation depending on AH form. The results of testing baroreflex by BP reduction in the group of SH patients point to the absence of efficient reactions of systemic circulation. In EH, circulation reacts extra actively. The condition of the cardiovascular system in SH is characterized by marked amplitude hypertension and asynchronous 24-h rhythm of vegetative impacts on the myocardium in the presence of subnormal afferentation of carotid receptors. CONCLUSION: The baroreflex control of the cardiovascular system in various forms of AH differs from that of normotensive subjects. The baroreflex and parameters of 24-h profile of AP and VRH are correlated.

[Clinico-functional evaluation of hypotensive effect of carvedilol in elderly patients with mild and moderate arterial hypertension]. / Kliniko-funktsional'naia otsenka gipotenzivnogo éffekta karvedilola u lits pozhilogo vozrasta s miagkoi i umerennoi arterial'noi gipertoniei.

AIM: To study a hypotensive activity of carvedilol (dilatrend, Beringer Mannheim GMBH), its influence on 24-h profile of arterial pressure (AP), baroreceptor control of BP and vegetative regulation of the heart in elderly patients with mild and moderate arterial hypertension (AH). MATERIAL AND METHODS: A 3-week monotherapy with carvedilol in a single dose 25 mg/day was conducted in 47 elderly patients with mild or moderate isolated systolic or essential hypertension. The effect of the treatment was assessed by the data of synchronous 24-h monitoring of blood pressure (BP), ECG, by variability of the cardiac rhythm (Cardio Tens, Cardio Tens 01, Meditech, Hungary), baroreceptor regulation of BP (the study of synocarotid areas by the method of "cervical" camera). RESULTS: Carvedilol produced a positive trend in the clinicofunctional indices of the circulation. The hypotensive effect lasted 24 hours in 78.8% of the examinees. The drug had no negative effect on the circadian rhythm of AP, is active early in the morning, did not induce a rise in the hypotonic load or diagnostically significant deviation of ST segment, reduced AP variability, improved vegetative and baroreceptor regulation of blood circulation. CONCLUSION: Carvedilol in a dose 25 mg/day is an effective monotherapy of mild and moderate AH in elderly patients.

[Osmo-adalat in the treatment of isolated systolic and systolic-diastolic arterial hypertension in aged patients]. / Osmo-adalat v lechenii izolirovannoi sistolicheskoi i sistolodiastolicheskoi arterial'noi gipertonii u pozhilykh bol'nykh.

AIM: To examine efficiency and tolerance of osmo-adalat in monotherapy of mild and moderate arterial hypertension (AH) in the elderly. MATERIAL AND METHODS: 60 AH patients were randomized into two groups. Group 1 received osmo-adalat monotherapy in daily dose 30 mg for 3 weeks. These were 14 patients with isolated systolic AH (ISAH) and 16 patients with essential hypertension (EH). Of group 2 patients, 15 with ISAH and 15 with EH received cordipin in a dose 10 mg three times a day. All the patients underwent 24-h monitoring of arterial pressure, in 18 patients arterial pressure and ECG were registered in parallel for 24 hours. RESULTS: AH treatment with osmo-adalat is rather effective. This is proved by its positive effect on shifted profile of arterial pressure in patients with ISAH and EH. A fall of arterial pressure on the peak of osmo-adalat antihypertensive action is not associated with hypotonic overloading of target organs, myocardial ischemia and increased heart rate. A single intake of osmo-adalat provides a smooth circadian control of arterial pressure in elderly hypertensive patients, the end effect being 50% of the peak one. The drug is well tolerated. Side effects do not require osmo-adalat discontinuation. CONCLUSION: Osmo-adalat in a single daily dose 30 mg is effective and safe in the treatment of mild and moderate AH in elderly patients.