Peculiarities of Autonomic Regulation of the Heart in Experimental Normobaric Hypoxia of Different Genesis.

We compared autonomic regulation of the heart in Wistar rats with acute exogenous hypoxic and chronic normobaric hypoxia against the background of experimental chronic obstructive pulmonary disease. In animals subjected to normobaric hypoxia, dysfunction of the autonomic regulation of the heart developed; it manifested in a significant limitation of the effects of the parasympathetic and sympathetic nervous systems on the pacemaker activity of the sinoatrial node. Disturbances in autonomic regulation of the heart in acute exogenous hypoxic normobaric hypoxia were characterized by "rigid" heart rhythm and bradycardia in the presence of systolic-diastolic arterial hypotension. Centralization of heart rhythm control did not provide compensation for hemodynamic disturbances. In case of chronic normobaric hypoxia, an increase in arterial hypoxemia was associated with protective "denervation" of the heart against the background of increased activity of the humoral regulation, which manifested in tachycardia, isolated systolic arterial hypertension, and overstrain of regulatory systems.

[The behavioral status of rats with experimental comorbidity of chronic obstructive pulmonarydisease and acute cerebral ischemia]. / Povedencheskii status krys pri éksperimental'noi komorbidnosti khronicheskoi obstruktivnoi bolezni legkikh i ostroi ishemii golovnogo mozga.

AIM: To compare behavioral patterns of rats with experimental chronic obstructive pulmonary disease (ECOPD), acute cerebral ischemia (ACI) and a combination of these pathologies. MATERIAL AND METHODS: The study included 70 male Wistar rats (weight 250-300 g) divided into 5 groups. ECOPD was modeled by a combination of inducers (purified papain and bacterial lipopolysaccharide), and ACI by a single-stage bilateral occlusion of common carotid arteries. The neurological status was assessed with NSS, and the behavioral status was assessed using the battery of tests including 'open field', 'radial eight-arm labyrinth', 'O-shaped elevated labyrinth'. RESULTS AND CONCLUSION: With the combination of ECOPD and ACI, a minimal (20%) survival rate of animals and the maximum severity of neurological and behavioral disorders, were recorded. The latter were characterized by a sharp restriction of locomotor and research activity, spatial memory, high anxiety and increasing autonomic imbalance. Survival rate of rats with isolated ACI was 35%, and disturbances of their neurological and behavioral status were moderately expressed. In rats with isolated ECOPD, the neurological deficit was mild. Behavioral disorders were manifested by a moderate limitation of locomotor function, a slight increase in anxiety with preserved research activity and spatial memory. The results of the study indicate the relevance of the respiratory and cerebrovascular comorbidity model for assessing changes in physiological functions and their subsequent correction.

[Morphofunctional features of the cerebral cortex in chronic obstructive pulmonary disease concurrent with ischemic stroke]. / Morfofunktsional'nye osobennosti kory bol'shikh polusharii mozga pri sochetanii khronicheskoi obstruktivnoi bolezni legkikh i ishemicheskogo insul'ta.

OBJECTIVE: To determine the structural changes in the cerebral cortex tissues, which are characteristic of the severe course of chronic obstructive pulmonary disease (COPD) and ischemic cerebral stroke (ICS). MATERIAL AND METHODS: The autopsy material of the microcirculatory bed of the cerebral cortex from 18 people aged 48-64 years who had died from COPD, ICS, and a concurrence of these conditions underwent histological examination and morphometric analysis. RESULTS: The state of the brain from the persons who died from ICS was characterized by a decline in the total number of neurons and glial elements, by structural and regional blood flow changes with obvious venous hyperemia, stasis, and red blood cell aggregation in the vessels. There was pericellular and perivascular edema in the perifocal area of the brain from people who died from COPD, as well as morphological signs of cerebral hemodynamic disorders. The brain structural features in ICS concurrent with COPD included a double decrease in the numerical density of capillaries, their hyperemia, perivascular edema, and venous plethora, a substantial change in the diameter of non-muscular venules, parenchymal atrophy, and stromal sclerosis, indicating the presence of a chronic process. CONCLUSION: Patients with ICS in the presence of COPD versus those who died from the isolated variants of these conditions were recorded to have an obvious decrease in the numerical density of capillaries, their hyperemia, and a pronounced change in the structure of the cerebral vein wall, which is a consequence of multisystem processes associated with COPD.

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.

Chronic obstructive pulmonary disease and cerebrovascular diseases: functional and clinical aspect of comorbidity.

Literature data of chronic obstructive pulmonary disease (COPD) and cerebrovascular diseases (CVD) comorbidity are represented in this review. Key aspects of this interaction and its importance for clinical medicine have been considered. CVD and COPD are the main mortality factors in adults, which contribute to great economic wastes. The incidence of chronic cerebral ischemia for COPD patients is almost three times as high as for general population. The incidence of ischemic stroke for COPD patients is 1,2 times higher than in general population. For hemorrhagic stroke and subarachnoid haemorrhages, this figures are 1,3 and 1,46 respectively. Chronic systemic inflammation, tissue hypoxia and oxidative stress play the crucial role in respiratory and cerebrovascular comorbidity. Metabolites of these processes (especially proinflammatory cytokines, reactive oxygen species, C-reactive protein and some neurotrophins) increase the permeability of blood-brain barrier, destroy brain cells and activate atherogenesis in pre- and intracerebral arteries. Endothelial dysfunction affects autoregulation of cerebral circulation. Systemic symptoms of COPD are closely associated with different structural-functional disorders of the brain such as reduction in white matter integrity, grey matter volume reduction and cerebral microbleeds. Also, venous encephalopathy is developed as a result of intrathoracic pressure elevation and stasis in superior vena cava system. These processes result in neurological symptomatology. The intensity of symptoms depends on COPD severity. The occurrence of cognitive impairment, psychic tension, depression, panic disorders also increases. However COPD and CVD comorbidity is an important problem of modern medicine, pathophysiologic mechanisms and clinic aspects of this problem remain unresolved. Understanding of their role opens perspectives for rational pharmacotherapy.