The use of information process indices for the prediction of sympathectomy efficiency in complex regional pain syndrome

The key role of information processes for ensuring the optimal sanogenesis in humans was shown by the wavelet-analysis of skin microvascular blood flow oscillations in 64 patients with complex regional pain syndrome after sympathectomy. The early reorganization of information in the trophotropic direction at the level of microvascular tissue systems, and its predominance and preservation along the microvascular networks facilitate optimal adaptive reactions and, as a result, are conducive to maximum treatment efficiency. In these cases, the complete elimination of disease and the achievement of excellent treatment results are possible. The maximum treatment efficiency could not be reached without the above-mentioned informational changes. On the contrary, the predominance and preservation of ergotropic information in the early periods after surgery were unfavorable for the prediction of the clinical outcome of sympathectomy. Tissue sympathectomy is not required for the formation of the trophotropic type of information exchange in microvascular networks; it is enough to achieve a certain threshold of a sympathetic activity decrease. The results obtained may be useful for investigating the physiological mechanisms of informational treatment technologies (homeopathy etc.).     

The problem of information value in microvascular networks

A novel methodology of quantitative estimation of the information value in microvascular networks is proposed. The methodology has been developed on the basis of the results of wavelet analysis of skin blood flow oscillations measured by means of laser Doppler flowmetry (LDF) in 30 healthy subjects and 56 patients with hand diseases or consequences of hand injuries. The method is based on the calculation of the relative indices of information preservation, dominance of the preserved information, and information effectiveness. The deviation from the multistable information regimen is the largest in the case of resonance oscillations: the total information quantity is significantly decreased; however, the preservation of dominant information and its effectiveness are improved. The preservation of trophic myogenic information predominates upon reduction of sympathetic influences. An increase in the number of information channels increases only the information quantity, whereas the degree of its preservation varies. Sensory peptidergic nerve fibers are activated in response to local heating of the dorsal forearm skin to 34°C. This information is the most effective at the beginning of the heating, when the blood flow increases to a plateau. The blood flow oscillations represented in the wavelet spectrum of microcirculatory oscillations serve as operators based on effective information. These oscillations not only play the hemodynamic role, but also carry information in microvascular networks.     

The use of information processes indices for prediction of sympathectomy efficiency in complex regional pain syndrome

Key significance of information processes for ensuring optimal sanogenesis was shown by wavelet-analysis of skin microvascular blood flow oscillations at 64 patients with complex regional pain syndrome after sympathectomy Early reorganization of information in trophotropic direction at the level of microvascular tissue systems, its predomination and conservation all along the microvascular networks facilitate optimal realization of adaptive reactions and, as a result, are conductive to maximum treatment efficiency. In these cases complete elimination of disease and achievement of excellent treatment results were possible. Maximum treatment efficiency could not be reached without the above-mentioned information changing. On the contrary predomination and conservation of ergotropic information at the early periods after surgery were unfavourable to prediction of clinical results of sympathectomy Tissue desympathisation is not required to formation of information trophotropic purposefulness in microvascular networks; it is enough to achieve certain threshold of sympathetic activity decrease. The results of this work may be useful for investigation of physiological mechanisms of information treatment technologies (homeopathy etc.).     

The problem of adaptation and oscillatory processes in the microvascular bed

Healthy people (n = 16), patients with autonomic dystonia syndrome (n = 38), and patients with traumatic rupture of the median nerve before and after nerve suture (n = 28) were examined by laser Doppler flowmetry (LDF) with a computer wavelet analysis of blood flow oscillations. Functional states (FSs) of the microcirculatory bed wеre assessed using energetic and information indices of microvascular blood flow oscillations. The variation coefficient and the information regime (multistable or resonance) were used as key characteristics. Oscillatory processes are an integral part of adaptation and the FS formation in the microvascular bed. FSs were classified as adaptive, hyperadaptive, hypoadaptive, and failure of adaptation. Because supporting the optimal function of nutritive microvessels is a leading component of the adaptation process, FSs of nutritive and nonnutritive microvessels may differ. A selective contribution of the autonomic sympathetic regulatory channel was related to maintaining considerable hyperadaptation in the microvascular bed with overstrain or marked overstrain of regulatory systems, as in emotional stress. Hypoadaptive FSs formed when skin blood flow increased, an excess decrease in flow resistance was unnecessary, and especially when regulatory factors were in deficiency, e.g., in neurodystrophic syndrome.     

Innervation of the carotid body. An experimental quantitative study

The innervation of the carotid body in the cat was studied by means of light- and electron-microscopic techniques. Sinus nerve resection, glossopharyngeal resection, bilateral cervical sympathectomy, excisions of two nerves, and injection of 6-hydroxydopamine (6-OH-DA) were performed in different groups of animals. It was found that resection of the sinus nerve produces a rapid phase of degeneration of intralobular fibers and synaptic boutons, followed by a reinnervation with a progressive reappearance of these elements. This reinnervation is retarded by sympathectomy and prevented by 6-OH-DA. It is therefore concluded that reinnervation is due to collateral regeneration of nearby sympathetic fibers. Resection of the sinus nerve produces an increase in the number of argentaffin cells and dense-cored vesicles in the cytoplasm of principal cells. These findings suggest the existence of efferent synaptic contacts between this nerve and principal cells. Part of the intralobular fibers and synaptic boutons degenerate after bilateral sympathectomy demonstrating that sympathetic axons connect synaptically to the principal cells. Sympathetic fibers reach the carotid body, not only from branches of the cervical plexuses but also from fibers running in the adventitia of the common carotid artery, and via glossopharyngeal and sinus nerves. The vagus nerve contributes a few fibers to the parenchymal lobules of the carotid body.     

Organization of the guinea-pig uterine innervation. Distribution of immunoreactivities for different neuronal markers. Effects of chemical- and pregnancy-induced sympathectomy

Summary The structural organization of the guinea-pig uterine innervation was investigated by an immunofluorescence method using neurofibrillary protein (NF) and neuron-specific enolase (NSE) as general neuronal markers. NF- and NSE-immunoreactive nerve trunks and non-varicose nerves formed continuous networks similar to nerves with analogue morphology and with immunoreactivities for tyrosine hydroxylase (TH; adrenergic nerves) and neuropeptide Y (NPY). NF- and NSE-immunoreactive non-varicose nerves occurred in the myometrium and along vessels, where TH- and NPY-immunoreactive varicose nerves were also comparatively frequent. After chemical sympathectomy all TH- and NPY-immunoreactive varicose nerves and most NF- and NSE-immunoreactive non-varicose nerves disappeared, suggesting colocalization of TH, NPY, NF and NSE immunoreactivities. During pregnancy all NF-, NSE-, TH- and NPY-immunoreactive nerve structures disappeared in the foetus-bearing uterine horns whereas in the cervix and non-foetus-bearing uterine horns only the myometrial TH- and NPY-immunoreactive varicose nerves disappeared. After parturition there was a complete structural restoration of all types of immunoreactive nerves in previously non-foetus-related tissue. The reinnervation of this tissue followed a similar time-course to that after chemical sympathectomy. In contrast, the reinnervation of previously foetus-related tissue was much slower and incomplete.In conclusion, the whole autonomic uterine innervation undergoes overt structural changes during pregnancy and these changes are related to the foetus-bearing regions.     

Geomagnetic field modulates artificial static magnetic field effect on arterial baroreflex and on microcirculation

Spreading evidence suggests that geomagnetic field (GMF) modulates artificial magnetic fields biological effect and associated with increased cardiovascular morbidity. To explore the underlying physiological mechanism we studied 350 mT static magnetic field (SMF) effect on arterial baroreflex-mediated skin microcirculatory response in conjunction with actual geomagnetic activity, reflected by K and K _p indices. Fourteen experiments were performed in rabbits sedated by pentobarbital infusion (5 mg/kg/h). Mean femoral artery blood pressure, heart rate, and the ear lobe skin microcirculatory blood flow, measured by microphotoelectric plethysmogram (MPPG), were simultaneously recorded before and after 40 min of NdFeB magnets local exposure to sinocarotid baroreceptors. Arterial baroreflex sensitivity (BRS) was estimated from heart rate/blood pressure response to intravenous bolus injections of nitroprusside and phenylephrine. We found a significant positive correlation between SMF-induced increase in BRS and increment in microvascular blood flow (ΔBRS with ΔMPPG, r=0.7, p<0.009) indicated the participation of the arterial baroreflex in the regulation of the microcirculation and its enhancement after SMF exposure. Geomagnetic disturbance, as opposed to SMF, decreased both microcirculation and BRS, and counteracted SMF-induced increment in microcirculatory blood flow (K-index with ΔMPPG; r _s=−0.55, p<0.041). GMF probably affected central baroreflex pathways, diminishing SMF direct stimulatory effect on sinocarotid baroreceptors and on baroreflex-mediated vasodilatatory response. The results herein may thus point to arterial baroreflex as a possible physiological mechanism for magnetic-field cardiovascular effect. It seems that geomagnetic disturbance modifies artificial magnetic fields biological effect and should be taken into consideration in the assessment of the final effect. An erratum to this article can be found at     

Blood flow oscillations at a frequency of about 0.1 Hz in skin microvessels do not reflect the sympathetic regulation of their tone

Wavelet analysis of blood flow oscillations recorded with laser Doppler flowmetry in finger glabrous skin microvessels was carried out in 82 subjects with different variations in the syndromes of hand and foot sympathectomy and denervation. As distinct from the 0.02–0.046-Hz (about 0.03–0.04 Hz) blood flow oscillations in skin microvessels of sympathetic thermoregulatory origin, no relationship was found between the presence of 0.07–0.015 Hz (about 0.1 Hz) vasomotions in the wavelet spectrum and intactness of sympathetic innervation in the tissue region. The use of the myogenic band oscillation parameters, in particular, the amplitudes of vasomotions, for assessing the state of sympathetic thermoregulatory innervation determining the neurogenic tone of skin microvessels is not physiologically correct. The influence of local environmental factors on the vasomotion parameters confirms their local origin. The local perfusion pressure value significantly influenced the amplitude but not the frequency of vasomotions. The amplitude dominance of vasomotions was observed upon a decrease in perfusion pressure, whereas a marked increase in perfusion pressure or venous congestion resulted in a sharp depression of their amplitudes. Under the sympathectomy conditions, the oscillatory dynamic component of the arteriolar myogenic tone in the glabrous skin of the extremity acral zones is involved in the blood flow’s autoregulation. The presence of fine sensory fibers is necessary to carry out the dynamic autoregulation of the blood flow. Sensory nonmyelinated fibers and the trophic neuropeptides secreted by them not only initiate independent oscillations in the low-frequency (0.047–0.069 Hz) myogenic band, but also contribute to the normalized amplitudes of vasomotions being increased. At the same time, no appreciable influence of the sympathetic vasomotor activity and the corresponding influence of catecholamines on the amplitude and frequency of vasomotions was observed.     

Trophic interactions between sensory nerves and their targets

Neurotrophins are target-derived trophic factors essential for the survival and maintenance of neurons. Among these, nerve growth factor (NGF) and neurotrophin-3 (NT-3) are particularly important for sensory neurons. The actions of neurotrophins are through the p75 low-affinity receptor and the high-affinity receptor tyrosine kinase(trk). Each neurotrophin has its preferred receptor, i.e.trkA for NGF, andtrkC for NT-3. The primary sensory neurons in the dorsal root ganglion are classified into two categories, namely, the large and small sensory neurons based on their size. The large sensory neurons with the expression oftrkC depend on NT-3 for development and subserve the function of position sensations. Some of the small sensory neurons expresstrkA and are NGF-dependent. They are responsible for nociceptive sensation, the detection of painful and thermal stimuli. A more intriguing observation is the bidirectional interactions between nociceptive nerves and their target, the skin. The peripheral processes of small sensory neurons innervate the epidermis of the skin as free nerve endings. In denervated skin, there is a drastic reduction in the epidermal thickness, a finding corroborated by the phenomenon of trophic change, the shining and thinning of the skin, in the disorders of peripheral nerves. The performance of animals with peripheral nerve disorders improved after administration of neurotrophic factors. Based on these results, the therapeutic potentials of neurotrophic factors in human are under investigation.     

Angiogenesis and nerve regeneration in a model of human skin equivalent transplant

The angiogenesis and reinnervation were studied in a porcine model of human skin equivalent (SE) graft and the relationship between the two processes was investigated. Confocal laser scanning microscopy was used to monitor, during the healing process, the pattern of vascularization and reinnervation at different time points. The SE was obtained by co-culturing fibroblasts and keratinocytes on a collagen-glycosaminoglycan-chitosan biopolymer and grafted on dorsal wounds generated by full-thickness resection in 25/30 Kg Large white pigs. Frozen sections were obtained from biopsies performed in autograft and xenograft, then were immunolabeled by using the endothelial marker lectin Lactifolia and with the neuronal marker gene product PGP9.5. Cajal staining was also used to visualize the nerve fibers. The results show that the vascularization precedes the innervation process. These data are consistent with the view that the development of nervous tissue is driven by nutritional and trophic factors provided by the vascular system. The arborization of the two systems observed during the third week from the graft might play a key role in maintaining the healing process and the graft survival.     

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.     

Cardiac and respiratory oscillations of the blood flow in microvessels of the human skin

Laser Doppler flowmetry with wavelet analysis, spectrophotometry, computer-aided capillaroscopy, and thermometry were used to study cardiac and respiratory oscillations of the blood flow in the skin microvessels of 30 subjects. The amplitudes of the cardiac and respiratory rhythms (A_c and A_r, respectively) were found to be determined predominantly by the distribution of perfusion and pressure in larger vessels (arterioles and venules). The cardiorespiratory coupling is a regulatory factor in the microcirculatory system; at rest, the value of A_c/A_r reflects the capillary arteriovenous ratio. In the structure of the microcirculation index (MI) and A_c, the velocity-to-volume ratio depends on the perfusion of the corresponding skin region: at rest, the volume-related component is expressed only in the skin with arteriolovenular anastomoses, whereas, in the skin without these anastomoses, MI and A_c are predominantly correlated with the dynamic velocity-related component. A_c is inversely dependent on both stationary and oscillatory components of the microvascular tone. The nature of the respiratory wave depends not only on the respiratory modulation of the venous outflow, but also on the perfusion pressure in the microvessels and venular hematocrit. The correlation of A_r with the total blood flow in the skin microvessels and the individual contributions of velocity-and volume-related components to A_r were significant only in situations where the blood flow was above a certain threshold, below which the respiratory waves can penetrate into the microvessels but their correlation with the total perfusion is nonsignificant.     

The nerve impulse in the axon — a new theory

The Classical Theory of function in the nervous system postulates that the nerve impulse is the result of a sequential reversal of the membrane potential due to an increased permeability of the membrane, first to sodium ions, then to potassium ions. The new theory presents a bio-physical model which depicts the nerve impulse as an event involving the motions of electrons and waves, and their interactions with sodium and potassium atoms and ions. The velocity of the nerve impulse (the most important parameter of nerve function) is determined by the product of two constants: c = the speed of light, which is a constant for all nerves; k =a constant for each nerve and is believed to be a specific property of nerve matter related in some way to the atomic process. The theory proposes that the nerve impulse in the axon is dualistic in nature (particles and waves play equally significant roles). The dualistic nature accounts for the three most fundamental characteristics of conduction of the nerve impulse: periodicity (conduction of a nerve impulse over long distances with constant velocity and form); non-summing (two nerve impulses cannot be in the same place at the same time); quantum nature of each nerve impulse — i.e., the unit message of the nerve impulse is an indivisible unit.     

Reinnervation of adult muscle in organ culture restores tetrodotoxin sensitivity in the absence of electrical activity.

Strips of denervated adult mouse diaphragm muscle maintained in organ culture were reinnervated by nerve processes growing out from explants of embryonic mouse spinal cord. In vivo, following denervation, the action potential loses its sensitivity to tetrodotoxin; this sensitivity is regained upon reinnervation. Similarly, action potentials in cultured muscle fibres were insensitive to tetrodotoxin, and sensitivity was restored in muscle fibres that became reinnervated in vitro. Tetrodotoxin sensitivity was also restored in cultured muscle fibres reinnervated in the continuous presence of d-tubocurarine, but it was not induced by 4 days of direct electrical stimulation of noninnervated muscles. We conclude that developing nerve terminals can exert a trophic action on adult muscle fibres that is independent of electrical activity in the muscle.     

A mathematical model for the distribution of hemodynamic parameters in the human retinal microvascular network

To quantitatively assess the arteriovenous distribution of hemodynamic parameters throughout the microvascular network of the human retina, we constructed a retinal microcirculatory model consisting of a dichotomous symmetric branching system. This system is characterized by a diameter exponent of 2.85, instead of 3 as dictated by Murray’s law, except for the capillary networks. The value of 2.85 was the sum of a fractal dimension (1.70) and a branch exponent (1.15) of the retinal vasculature. Following the feeding artery (central retinal artery), each bifurcation was recursively developed at a distance of an individual branch length [L(r) = 7.4r ^1.15] by a centrifugal scheme. The venular tree was formed in the same way. Using this model, we evaluated hemodynamic parameters, including blood pressure, blood flow, blood velocity, shear rate, and shear stress, within the retinal microcirculatory network as a function of vessel diameter. The arteriovenous distributions of blood pressure and velocity in the simulation were consistent with in vivo measurements in the human retina and other vascular beds of small animals. We therefore conclude that the current theoretical model was useful for quantifying hemodynamics as a function of vessel diameter within the retinal microvascular network.     

Nonlinear dynamics and information processing in pacemaker neurons

The paper treats some nonlinear dynamic phenomena in oscillatory activity of a single nerve cell. Based on experiments with CNS bursting pacemaker neurons ofHelix pomatia snail, a mathematical model was studied. The model demonstrates the majority of experimentally observable phenomena and allows one to investigate the role of its separate components. The phenomena demonstrated by model neuron (chaotic behavior, bistability, and sensitivity to parameter variations, initial conditions, and stimuli) may be relevant to information processing in nerve cells. The complexity of [Ca²⁺] _in −V phase diagrams of initial conditions depends on parameters. Transient synaptic impulse produces stable parameter-independent changes in activity of model neuron. These results indicate that a single bursting neuron can work in the neuronal ensemble as a dynamic switch. The sensitivity of this switch is regulated by a neurotransmitter.     

交感神经损毁术对自发性高血压大鼠血压和红细胞Na~＋外流动力学的影响

本实验研究了皮下注射６—羟多巴胺（６—ＯＨＤＡ）施行交感神经损毁术对成年自发性高血压大鼠（ＳＨＲ）血压和红细胞Ｎａ＋外流动力学的影响。结果表明,在幼年期施行交感神经损毁术的ＳＨＲ血压显著低于未损毁组,同时红细胞Ｎａ泵驱动的的Ｎａ＋外流最大速率显著下降、Ｎａ＋－Ｋ＋外向协同转运系统的单位活性升高。三者均接近ＷＫＹ大鼠的测定值。相反,损毁成年ＳＨＲ交感神经不影响上述两个动力学参数,血压也未见明显改变。此外,不论幼年或成年期注射６—ＯＨＤＡ均可降低Ｎａ＋—Ｌｉ＋对向转运系统驱动的Ｎａ＋外流最大速率。上述结果提示,在ＳＨＲ早期发育过程中,交感神经营养因子可能降低Ｎａ＋—Ｋ＋外向协同转运活性,继而刺激Ｎａ泵代偿功能增强。这种现象可能同时存在于ＳＨＲ动脉平滑肌,因而是高血压产生的一个原因。关于交感神经损毁术后ＳＨＲ红细胞Ｎａ＋—Ｌｉ＋对向转运最大速率下降的机制尚不清楚,但与交感神经早期营养作用的消除无关。     

Synaptic function in the nervous system: A theory and its application

The objective of this paper is to present a new theory of synaptic function in the nervous system. The basis for this theory is the experimental demonstration that a nerve impulse assumes five different forms as it advances through the synaptic region, and that five basic mathematical operations have been identified as being involved in the transformation of one form into another form. As a result of these data, the synaptic region is regarded as a functional unit where information coming to it is unpacked, processed, stored, and retrieved for transit to another synaptic region or effector site. The data also suggests that a nerve impulse is a bolus of energy, therefore, without substance; that it contains information coded in its shape or form; that it is precisely described mathematically. Furthermore, the data suggests synaptic regions process these nerve impulses by applying mathematical operations to them; that function in the synaptic region is highly stereotyped (programmed); that chemical substances are associated with the mathematical operations. The basic approach of this theory is to regard a significant portion of the nervous system as an interface between the external universe and man himself. As an interface, the nervous system receives and processes information from both the external universe and man himself in a programmed manner. The interface functions by converting the information it receives into a bolus of energy, the nerve impulse, then processes the bolus by converting it into numbers or functions and applying mathematical operation to it.     

Characteristics of the formation of temperature information in afferent units

The impulse activity of single afferent fibers of the dorsal roots of the cat spinal cord is studied for local mechanical, heat, and cold influences on the skin receptor fields. A probability analysis of the impulse flux suggests that a change occurs in the distributions of the intervals between impulses in accordance with the stimuli presented, regardless of the variations in the mean frequency of impulsation. It is hypothesized that the afferent fibers acquire polyfunctional properties on account of their multichannel information.Institute of Physiology, Kazakhstan, Academy of Sciences, Alma-Ata. Translated from Neirofiziologiya, Vol. 24, No. 5, pp. 582–591, September–October, 1992.     

Static magnetic field effect on the arterial baroreflex-mediated control of microcirculation: implications for cardiovascular effects due to environmental magnetic fields

Increasing evidence suggests that time-varying and static magnetic fields in the environment might affect the cardiovascular system. To explore the underlying physiology, the effect of static magnetic fields (SMFs) on the carotid baroreflex control of microcirculation was studied. Twenty-four hemodynamic monitorings were performed in rabbits sedated by pentobarbital infusion (5 mg/kg/h) during experiments that lasted 120 min. Mean femoral artery blood pressure, heart rate, and ear lobe skin microcirculatory blood flow, measured by microphotoelectric plethysmogram (MPPG), were simultaneously recorded before and after a 40 min exposure of the sinocarotid baroreceptors to Nd₂–Fe₁₄–B alloy magnets (n = 14) or sham magnets (n = 10, control series). The local SMF field was 350 mT, at the baroreceptors’ site. Arterial baroreflex sensitivity (BRS) was estimated from heart rate/blood pressure response to intravenous bolus injections of nitroprusside and phenylephrine. A significant positive correlation was found between the SMF-induced increase in BRS (ΔBRS = BRS_afterSMF − BRS_priorSMF) and the increment in microvascular blood flow (ΔMPPG = MPPG_afterSMF − MPPG_priorSMF) (r = 0.66, p < 0.009). The SMF probably modulated the arterial baroreflex-mediated microcirculatory control. This could represent one possible mechanism how environmental magnetic fields act on the cardiovascular system, and a method how to complexly adjust macro- and microcirculation with potential clinical implementation.