Structure of the venous and lymphatic beds of the heart and their alteration in experimental pathology

The investigation performed has demonstrated that under a great deal of coronary, pulmonary and other organs' disorders, in the venous and lymphatic beds of the heart compensatory-adaptive and pathological changes occur. The earliest and deepest changes are noted in the microcirculatory bed. Most of morphological signs on vascular reconstruction are not specific and are observed at different kinds of clinical and experimental pathology. Changes in venous and lymphatic vessels of pathological conditions& do not only result from damage in the organ's wall or hemodynamical changes in the cavities of the cardiac vessels but they themselves can cause some disturbances in the miocardial microcirculation intensifying its hypoxia, congestive symptoms and enhancing the development of decompensation in the organ.     

Development of the uterine microcirculatory bed in postnatal ontogeny

Age peculiarities of common structure of the microcirculatory pathways, specific volumes and amount of microvessels, zonal parameters of pericapillary microcirculation of metabolites, glycosamine glycans and glycoproteins contents, phosphatase and ATPase activity, collagen and elastic fibers of the microcirculatory bed vessels have been studied in 190 unchanged uteri, beginning from 36-week-old fetuses up to 35 years of age. The microcirculatory bed of myometrium during the period of postnatal ontogenesis investigated possesses a polymer-homonomous structural organization; its base make myoangiomas, including the terminal arteriole with precapillaries and collecting venule, that run from it. Similar structure of the myometrium microcirculatory pathways is already observed in fetuses of late antenatal period. In endometrium formed glanduloangionomas are revealed in the prepubertal age. Increase in glycosamine glycans contents is stated in the microvessel walls and in the uterine stroma during the process of its development. Compensatory-adaptive changes in the uterine microcirculatory bed are described during the newborn period up to the puberty. Functionally mature structures of the microcirculatory pathways in the submucosal and vascular layers of myometrium, endometrium and in the cervix uteri are found to be formed earlier than in other areas of the organ.     

Static magnetic field effect on microcirculation,direct versus baroreflex-mediated approach

We compared in conscious rabbits, sedated using pentobarbital intravenous (i.v.) infusion (5 mg kg^{? 1} h^{? 1}), the effect of a static magnetic field (SMF), generated by Nd₂–Fe₁₄–B magnets, on microcirculation during its 40 min local exposure to the microvascular network in cutaneous tissue [20 sham exposure and 20 SMF (0.25 T) exposure runs] or to sinocarotid baroreceptors [14 sham exposure and 14 SMF (0.35 T) exposure runs]. Mean femoral artery blood pressure (BP), heart rate (HR), arterial baroreflex sensitivity (BRS), assessed from HR and BP responses to i.v. bolus of nitroprusside and phenylephrine, and microcirculatory blood flow, using microphotoelectric plethysmography (MPPG), were simultaneously monitored. SMF significantly increased microcirculation on a 17.8% in microvascular and on a 23.3% in baroreceptor exposure series. In baroreceptor exposure series, SMF significantly decreased BP, increased heart rate variability, BRS and sodium nitroprusside (NO-donor) i.v. bolus microcirculatory vasodilatory effect. These suggest augmentation of the arterial baroreflex capacity support NO-dependent vasodilation, by increased sensitivity of vessels to NO, to be a new physiological mechanism of BP buffering and microcirculatory control. A significant positive correlation was also found between increase in BRS and in MPPG (r = 0.66, p < 0.009), indicating baroreflex participation in the regulation of the microcirculation and its enhancement after SMF exposure. Both direct and baroreflex-mediated approaches demonstrate SMF significant vasodilatory effect with potential clinical implication in macro- and microcirculatory disorders.     

Functional and morphological basis for the nature of the microcirculatory bed reactions of the bulbar conjunctiva in experimental occlusion of the cranial mesenteric artery

A complex analysis on changes occurring in conjunctival microcirculation and a number of indices of hemodynamics, hemorheology and metabolism at different time of experimental occlusion in the cranial mesenteric artery has demonstrated certain objective and many-sided correlations that prove a systemic character of biomicroscopical changes in the conjunctiva. The degree of changes in the conjunctival microcirculation depends on duration of occlusion. After a 3 hours' occlusion revascularization is accompanied by reversible general microcirculatory disorders that are registered in bulboconjunctiva. In a 6 and 12 hours' occlusion revascularization is characterized by increasing general changes in microcirculation.     

Microcirculatory disorders in the connective tissue structures of certain organs in traumatic shock with acute hemorrhage]

The present work is a fragment of the author's complex study of replantation of an extremity in experiment. Experiments on reproduction of the model of traumatic shock with acute loss of blood under conditions of muscle relaxation proposed by Yu. V. Kiprenski were performed in 15 dogs and 10 cats. It was established that in animals dead as a result of shock there appeared severe disorders of microcirculation in tissues and organs. They were characterized by a pronounced spasm of the vessels of the arteriolar link and dilatation of the venular and lymph collectors of the microcirculation bed. Simultaneously a great number of arterio-venular anastomoses were opened through which the arterial blood was shunted partly to avoid constricted capillaries. In the vessels of the venular link of the microcirculatory bed there appeared aggregations of formed elements of blood and microemboles. In absence of specific complex therapy, as it was in our experiments, the animals die of shock within the period from 17 min to 5 hour 20 min.     

The State of the Regional Blood Flow in the Upper Extremity after Dosed Physical Exercise

The effect of local isometric exercise on hand and forearm blood flow was studied. With maximum muscular exercise performed by both males and females, a decrease in hand and forearm blood flow was due to vasoconstriction caused by the mechanical pressure of working muscles. With 75 and 50% loads, marked hyperemia was observed in the main and microcirculatory vessels in the hand and forearm, which was rather long-lasting in the hand because of the difficulty of the forearm venous outflow. The minimum loads affected mainly the microcirculation, and no significant hemodynamic changes in main vessels were observed. The exercise performed at 50% of maximum muscular force was taken as an optimum load in kinesotherapeutic programs.     

微循环阻力指数在心血管疾病中的应用

随着医疗水平的发展,心血管疾病的诊断和治疗越来越规范和细致,不仅需要对心脏大血管进行评估,对微循环的评估也是十分重要。微循环阻力指数(index of microcirculatory resistance,IMR)是2003年由Fearon医生提出的一种操作方便、能真实反映微循环阻力的冠状动脉功能学定量评价指标。IMR的可重复性好,且不受冠状动脉狭窄影响,在预测围手术期心梗、PCI术后微血管阻塞、ST段抬高性心肌梗死患者PCI预后,评价PCI辅助治疗手段的有效性,阐明应激性心肌病的发病机制以及评价心血管药物的应用等方面具有重要意义。本文就IMR的特点及临床应用做一综述。     

Microcirculatory changes in the tissues surrounding a gunshot wound

An examination was carried out of microcirculation disorders as the main link of the pathogenetic process in the tissues surrounding a gunshot wound. Microcirculatory disorders were assessed in rabbits (924) with the help of radionuclide method (tissue radiometry and scannography) and the method of vital contact microscopy in gunshot wounds of posterior extremity soft tissues. After the injury the formation of four zones of tissue damage was revealed, with different character of microcirculatory changes in wound process dynamics. The obtained data may serve as the basis for working out zonal disorder classification and local treatment of gunshot wounds.     

Effects of Incretin-Based Therapies on Neuro-Cardiovascular Dynamic Changes Induced by High Fat Diet in Rats

Background and Aims

Obesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats.

Methods and Results

We have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling. High fat diet worsened biometric and metabolic parameters and promoted deleterious effects on autonomic, myocardial and haemodynamic parameters, decreased capillary diameters and increased functional capillary density in the brain. Biometric and metabolic parameters were better improved by glucagon like peptide-1 (GLP-1) compared with dipeptdyl peptidase-4 (DPP-4) inhibitor. On the other hand, both GLP-1 agonist and DPP-4 inhibitor reversed the deleterious effects of high fat diet on autonomic, myocardial, haemodynamic and cerebral microvascular parameters. GLP-1 agonist and DPP-4 inhibitor therapy also increased mitochondrial permeability transition pore resistance in brain and heart tissues of rats subjected to high fat diet.

Conclusion

Incretin-based therapies improve deleterious cardiovascular effects induced by high fat diet and may have important contributions on the interplay between neuro-cardiovascular dynamic controls through mitochondrial dysfunction associated to metabolic disorders.     

Blood aggregation and the system of microcirculation in experimental atherosclerosis, its spontaneous regression and hemosorption

Blood aggregate state and microcirculation were studied during development and spontaneous regression of experimental atherosclerosis and following hemosorption. It has been shown that experimental atherosclerosis is not only accompanied by changes in blood lipid composition, but also by disturbances in the structure and function of microcirculatory bed. Normalization of blood lipid composition and recovery of blood aggregate state and microcirculatory bed structure and function were not observed during spontaneous regression. Repeated hemosorption enhances atherosclerosis regression, normalizes lipid composition of blood and biological membranes and promotes the recovery of microcirculation.     

Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine Model

Background

Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status.

Objectives

To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance.

Methods

Healthy swine were randomized to receive by intracoronary route either 30x10⁶ MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups.

Results

CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted.

Conclusion

Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.     

Effects of verapamil on the development of pain syndrome in rats after section of the sciatic nerve]

The effect of daily verapamil administration (5 mg/kg) on pain sensitivity, bioelectric activity of cerebral cortex and microcirculation was studied in rats with cut sciatic nerve. Verapamil untreated rats showed hyperalgesia, autotomies and hypersynchronic discharges in contralateral hemisphere, increased range of evoked potentials and disorders in microcirculatory system which evidence developing pain syndrome. Early introduction of verapamil after the nerve cut prevented the emergence of pain syndrome.     

Nerve elements of the heart in aorto-coronary by-pass conditions.

Experiments were conducted on 100 dogs with creation of autovenous aortocoronary shunts in the coronary artery. The hearts were examined 1 year following surgery by routine histological, neurohistological, histochemical and electron-microscopic techniques. No severe destructive changes were revealed in the shunting system. The main process develop in the heart very early following surgery and consist in reactive changes in the intramural nerve elements, elevation of the phosphatase activity in the walls of the microcirculatory bed, redistribution of acid and neutral mucopolysaccharides and changes of permeability of the haematohistiocytic barriers; they are an adaptation response of the myocardium to operative stress and new conditions of influx of blood to the cardiac muscle.     

Patterns in the development of the ultrastructure of elements of the microcirculatory system in the early stages of human embryogenesis

By means of transmissive electron microscopy methods, general regularities in development of the microcirculatory system have been studied at early stages of the human prenatal ontogenesis in functionally different organs. Ultrastructure of two cell types has been described in the mesenchyme of human embryos. Formation mechanisms of the primary blood vessels belonging to the protocapillary type are revealed. Structural peculiarities of the primary protocapillary network differentiating into various links of the secondary organospecific hemomicrocirculatory bed are distinguished. Certain stageness in development of the microcirculatory system is stated, its blood circulatory compartment including. Two stages are determined in development of the microcirculatory system: prevascular and vascular microcirculation. The latter includes the precirculatory and circulatory phases.     

The microcirculatory bed of the human heart

Using a complex approach in studying microcirculatory bed of the human heart, possibilities of scanning electron microscopy of corrosive preparations, those of silver nitrate impregnation after V. V. Kuprianov are demonstrated. The silver nitrate impregnation makes it possible to study the wall structure of the microcirculatory pathways, to analyse arrangement of nuclei in the endothelial and muscle cells of the microcirculatory links, to reveal together with the vessels the surrounding tissues. Scanograms of the corrosive preparations of the arterioles demonstrate "circulatory strips", that are absent in the venular part. The relief of the luminal casts of the microcirculatory bed vessels in the human heart is presented as impresses of nuclei of the endothelial and smooth muscle cells. Peculiarities in form and distribution of these nuclei in various links of the microbed are demonstrated.     

Morphologic indices of the rat heart after colchicine application to the vagus nerve

By means of the light optic and electron microscopic methods atrial ganglia, myocytes, vessels of the right cardiac chambers have been studied in rats 2 days--3 weeks after application of 100 mcg of colchicine on the right nervus vagus. Certain changes of the neural fibers have been described at the area of the application. In the myocardium the microcirculatory bed, focal edema and hypoxic alterations of the myocyte ultrastructure have been revealed. In the ventrical ganglia destruction of some terminals of the preganglionar fibers, chromatolysis and vacuolization of single neurocytes, as well as intraganglionar granule-containing cells have been found. The changes described take place for 7 days and they nearly completely disappear in 10 days. A suggestion is made that some phenomena, in particular, destruction of the preganglionar fibers and changes of the cardiac microcirculatory bed are connected with certain disturbances of the quick transport of substances in the nervus vagus fibers.     

Effects of thermal factors on the state of microcirculation of the small intestine in acute ischemia

The influence of normo- (38 degrees C), hyper- (42 degrees C) and hypothermia (20 degrees C) on microcirculatory disturbances caused by acute local ischemia of the small intestine was investigated with the help of biomicroscopy as well as morphological methods. Ischemia was modeled by ligation of the intestine look eventrated through the abdominal wall incision of a rat onto the microscope stage for 1 h. It was shown that hyperthermia intensified microcirculatory disorders and stimulated destructive processes in tissues and hypothermia promoting microcirculation and decreasing metabolism and restrained the development of these processes. Important peculiarity of the microvascular response to ischemia, hyper- and hypothermia was revealed: heterogeneity of the reaction of different parts of microvascular bed. Appropriate evaluation of the microcirculation state in such conditions can be obtained taking into account not only the qualitative character of microvascular reaction but also an extent of this reaction manifestation in different parts of microvascular bed.     

The circulatory influence on development of age-related macular degeneration and hearing and equilibrium impairments

This study attempts to answer the question if any level of head and neck circulation takes a part in development of Age-Related Macular Degeneration (ARMD) and hearing and equilibrium impairments. Condition of large blood vessels was examined by Color-Doppler ultrasound, and carotid and ophthalmic arteries were included. The microcirculatory changes were examined directly by fundus photography and fluorescein angiography and indirectly testing hearing and equilibrium. The study group included 40 patients (21 females, 19 males) aging from 53 to 84 years with different stages of ARMD. The control group included 40 patients (18 females, 22 males) aging from 51 to 82 years without ARMD. Patients were inhabitants of Primorsko-Goranska County. There was no relationship between ARMD and condition of large blood vessels because significant stenosis of carotid arteries was found in 2 patients (5%) in study group and 3 patients (7.5%) in the control group (p > 0.05). On the contrary, we found correlation between ARMD and hearing (p = 0.0127) and equilibrium impairments (p = 0.0242). Fluorescein angiograms shows raised number of ischemic retinal capillaries in patients with ARMD (p = 0.0053). Results lead to conclusion that circulatory disorders on microcirculatory level take a great part in development of ARMD and hearing and equilibrium impairments in the elderly. The key is damage of sensory cells of the retina and inner ear caused by microcirculatory disorders. Interesting data was noticed that 9 patients with more serious ARMD on one side of head had greater hearing loss on the same side. If we find a new treatment for microcirculatory disorders, maybe we can treat both sensory impairments in earlier stage.     

Noninvasive in vivo assessment of the skeletal muscle and small intestine serous surface microcirculation in rat: sidestream dark-field (SDF) imaging

The pathophysiology of microcirculation is intensively investigated to understand disease development at the microscopic level. Orthogonal polarization spectral (OPS) imaging and its successor sidestream dark-field (SDF) imaging are relatively new noninvasive optical techniques allowing direct visualization of microcirculation in both clinical and experimental studies. The goal of this experimental study was to describe basic microcirculatory parameters of skeletal muscle and ileal serous surface microcirculation in the rat using SDF imaging and to standardize the technical aspects of the protocol. Interindividual variability in functional capillary density (FCD) and small vessels (<25 microm in diameter) proportion was determined in anesthetized rats on the surface of quadriceps femoris (m. rectus femoris and m. vastus medialis) and serous surface of ileum. Special custom made flexible arm was used to fix the SDF probe minimizing the pressure movement artifacts. Clear high contrast images were analyzed off-line. The mean FCD obtained from the surface of skeletal muscle and ileal serous surface was 219 (213-225 cm/cm(2)) and 290 (282-298 cm/cm(2)) respectively. There was no statistically significant difference between rats in mean values of FCD obtained from the muscle (P = 0.273) in contrast to ileal serous surface, where such difference was statistically significant (P = 0.036). No statistically significant differences in small vessels percentage was detected on either the muscle surface (P = 0.739) or on ileal serous surface (P = 0.659). Our study has shown that interindividual variability of basic microcirculatory parameters in rat skeletal muscle and ileum is acceptable when using SDF imaging technique according to a highly standardized protocol and with appropriate fixation device. SDF imaging represents promising technology for experimental and clinical studies.     

Changes in heart rate and circadian cardiac rhythm as physiological biomarkers for estimation of functional state of crayfish <Emphasis Type="Italic">Pontastacus leptodactylus</Emphasis> Esch. upon acidification of the environment

The changes in heart rate and circadian cardiac rhythm of crayfish Pontastacus leptodactylus Esch. kept in a lightning regime that is close to natural under optimal or low pH values were studied. The heart rate was registered in real time using an original noninvasive fiberoptic method. Upon acidification, disorders in circadian cardiac rhythm and organism reaction (by heart rate) in the suspension test were detected. The characteristics of cardiac activity are considered criteria for estimating the crayfish’s functional state at normal and stress conditions caused by the changes in the quality of the environment.