International journal of microcirculation, clinical and experimental最新文献

The reproducibility of laser Doppler flowmetry (LDF) in measuring the perfusion of the dental pulp was investigated. A second aim was to establish if the LDF signal from the dental pulp can be influenced by physiological stimuli, e.g. postural changes. A third aim was to apply the technique to clinical measurements of pulp perfusion in patients undergoing orthodontic therapy. A custom splint to position the probe was fabricated for 10 subjects, and measurements of pulpal perfusion in the maxillary six anterior teeth were repeated on eight occasions with the subject seated. Further, measurements of the dental pulp perfusion in one tooth were repeated with the subject in a standing and supine position. Mean perfusion (arbitrary perfusion units) for individual teeth varied from 2.7 for a central incisor to 15.5 for a lateral incisor. Perfusion was greatest for lateral incisors and least for central incisors. Pulpal perfusion was significantly higher in a supine than in a standing or sitting position. Initial clinical experience with LDF encourages further investigation of its potential as a diagnostic tool for determining pulp vitality. Preliminary experimental results suggest that LDF will be a valuable source indicating pulpal response to orthodontic therapy with fixed appliances.

Introduction: Biological signals like arterial blood pressure (ABP) and electrocardiograms are usually displayed in a linear fashion. The often very complex structure may, however, be better described by phase space plots and time-delayed vectors, enabling an advantageous display of the dynamics contained in the signal. The potentials of such a display were investigated during elective aortic aneurysm repair, where profound haemodynamic changes frequently occur.

Method: The peripheral volume pulse was recorded at a digit using noninvasive near infrared photoplethysmography (NIRP). All patients (n = 20, mean age 72.8 years) were invasively monitored using arterial and Swan Ganz catheters. The ABP signal was continuously recorded with a computer (sample rate 128 Hz). Two different phase space plots, [x(t), y(t + 8/128 s) and x(t), d(x(t + 8/128 s) - x(t))/dt] were calculated for the NIRP and the ABP signals and continuously displayed. The stability was subjectively assessed and the fractal dimension calculated using the 'Hausdorff dimension'. The correlation between stability, fractal dimension and frequently used parameters of patient monitoring were investigated.

Results: All patients included in the study had an uncomplicated operation. Cardiac index (CI) and oxygen delivery (DO2) increased, and systemic vascular resistance (SVR) decreased following declamping of the aorta. The ABP signal was generally more stable. After declamping of the aorta, 14 of 16 NIRP signals became unstable, and 9 of 14 ABP signals destabilised. The time required for stabilisation of the signal varied between the individual patients. Thirty minutes after declamping, 11 of 12 ABP signals were stable, whereas 3 out of 9 NIRP signals still revealed an unstable pattern. A fractal dimension was calculated by box counting, which revealed a linear regression over two orders of magnitude in a log-log plot (Hausdorff dimension between 1.19 and 1.71). The mean fractal dimension for NIRP was significantly higher than that of the ABP signal. On clamping and declamping of the aorta, a trend to a higher fractal dimension (p = 0.08) was observed for both signals analysed. No correlation was observed between the fractal dimension and ABP, SVR index, CI, DO2 index and oxygen consumption.

Discussion: The dynamic changes of the signals were emphasised when they were displayed as phase space plots calculated by time-delayed vectors. The time series of the signal revealed a fractal dimension, and the observed increase at the critical time points of the operation, where the need for cardiovascular regulation is most pronounced, support the contention that a physiological system based on non-linear behaviour may enable a rapid response to haemodynamic challenges. An on-line display of phase space plots calculated by time-delayed vectors may in future provide a valuable method of monitoring for high-risk p

The systemic effect of heparin fractions with mean molecular masses of 2.5, 5.0 and 16.4 kD on angiogenesis induced by vascular endothelial growth factor isoform 165 was studied using the truly quantitative rat mesenteric-window angiogenesis assay. The angiogenic treatment with 5 ml of VEGF165 at 480 pM was given intraperitoneally on days 0-4 and heparin fractions were given subcutaneously on days 0-13; animals were sacrificed on day 14. As the overlaps between the molecular mass distributions of the three fractions were relatively small, they essentially represent three different populations of heparin molecules. The doses of the heparins given were equal in terms of weight, but different in terms of the number of molecules and biologic activity. Angiogenesis was assessed in terms of vascularized area (VA), a measurement of microvascular spatial extension, and microvascular length (MVL), a measurement of microvascular density, using technically independent variables and image analysis. The total microvascular length was computed from VA x MVL. Treatment with the 5.0-kD fraction suppressed angiogenesis significantly in statistical terms compared with treatment with 2.5- and 16.4-kD heparins and the saline in controls. Interestingly, the 2.5-kD heparin fraction which was used here has previously been shown statistically significantly to suppress angiogenesis mediated by basic fibroblast growth factor in the same experimental system. Our data thus suggest that the systemic angiosuppressive effect of heparin in different mammalian angiogenic reactions is distinctly related to structural features such as molecular size.

This technical report describes the production and installation of a newly developed, one-piece, light-weight (0.6 g) access plexiglass chamber for the dorsal skin fold of the mouse.

Under normal conditions, the various vascular regulatory effector influences are interwoven in a dynamic, and not a static, circulatory system. The reaction of a smooth muscle cell is thus reflected only incompletely by the stationary activation curve 'developed tension versus membrane potential'. The missing time domain in this relationship is a reflection of our as yet limited understanding of the system's behavior in space and time. It should be emphasized that the rhythmogenic properties of vascular smooth muscle are closely coupled to a functioning circulation. The electrical and mechanical oscillations, which can be traced back to rhythmic activity of the active, electrogenic Na+/K+ pump, could originate in the allosteric qualities of the enzyme phosphofructokinase (PFK). Thus, PFK represents a rhythmogenic enzyme which may serve as an example of the connection between the biological properties on a molecular level and the spatiotemporal system's behavior. The cardiovascular system and its rhythmicity may be dominated by only a few control points, one of which is distinguished by the viscoelastic properties of a blood flow sensor macromolecule. Therefore, the three prominent control points - PFK, (Na+ + K+)-ATPase and flow sensor conformation - acting as negatively feedback-coupled, nonlinear synergetic order parameters, are sufficient to initiate the periodic events in the cardiovascular system and to provide a plausible explanation for their causal origin.

In immunological reactions, leukocytes need to travel from the intravascular space through the vessel wall into the surrounding tissue. The first step in this process is leukocyte rolling, which has often been studied in anesthetized animals. In this study, we investigated the effect of pentobarbital, Hypnorm and both components of the latter, fentanyl and fluanisone, on this primary leukocyte-endothelial cell interaction. Using intravital brightfield video microscopy, observations were made in postcapillary venules in the intact skin of the nailfold of trained conscious Lewis rats. Subsequently, the animals were anesthetized and observations were made in vivo. Leukocyte rolling was significantly elevated after injection of Hypnorm or fentanyl, while pentobarbital and fluanisone had no effect. None of the anesthetics affected leukocyte rolling velocity. Blood flow was significantly increased only after injection of Hypnorm and fluanisone. No correlation existed between the relative changes in leukocyte rolling and concomitant changes in blood flow. The results show that the level of leukocyte rolling can be affected by anesthetics. These changes are probably not mediated by changes in local hemodynamics. Pentobarbital anesthesia does not influence leukocyte rolling. Therefore, pentobarbital is a suitable anesthetic for observation of leukocyte rolling in skin. Hypnorm significantly increases the level of rolling in skin venules. This effect seems to be caused mainly by fentanyl.

The temporal dynamics of the systemic arterial pressure can be monitored noninvasively from the skin of the earlobe or forehead by photoplethysmography under the provision that the active control of the microcirculatory perfusion is eliminated. Using this approach, we have been able to detect a highly stable blood pressure rhythm in the range of 0.15 Hz during psychophysical relaxation or sleep. The aim of the present study was to investigate the occurrence and behavior of blood pressure rhythms below 0.2 Hz during general anesthesia. In 30 patients (ASA groups I-II) undergoing basic surgical procedures, photoplethysmographic recordings from the earlobe were made during the whole time of anesthesia. The recorded signals were divided into segments of 200 s of duration, the temporal structure of which was analyzed by fast Fourier transform. Different characteristic patterns of rhythmical behavior were detected: (1) absence of activity below 0.2 Hz ('low-frequency range'); (2) slow sinusoidal rhythmicity below 0.05 Hz; (3) 'chaotic' behavior, i.e. multiple incoherent fluctuations without stationary periods or amplitudes; (4) short-term rhythmical activity at about 0.15 Hz, and (5) long-term rhythmical activity at about 0.15 Hz. In patients sufficiently sedated to eliminate low-frequency activity, rhythmicity could sometimes be triggered by certain surgical stimuli, the response to which was suppressed by injection of opioids. The data presented strongly suggest that rhythmical perfusion patterns of the cutaneous microcirculation could serve as an indicator for the depth of anesthesia.

The use of intravital microscopy as a tool for studying the microcirculation has increased greatly over the last several decades. Early microscopes provided the first pictures of the microcirculation, but were cumbersome to use and subjected the tissue to a high light intensity, a problem which has recently become the subject of much discussion. The goal of this project was therefore to build a more ergodynamic microscope which minimizes the light exposure to the tissue. The automation of the microscope controls provides a platform on which other options can be built into the microscope, such as an autofocus feature. Furthermore, the use of the Optimas software also opens the possibility for on-line data processing.

The distribution of blood flow in the heart muscle is very heterogeneous and shows a self-similar fractal pattern, extending to small spatial scales. It is very likely that local oxygen consumption is more or less proportional to local blood flow and that local aerobic metabolism also is very heterogeneous. It is not yet clear whether local metabolism is heterogeneous in origin and the distribution of flow has secondarily adapted to metabolism, or, the other way around, whether flow is primarily heterogeneous because of the irregular structure of the coronary tree and flow has adapted to metabolism. Little is known yet about the developmental and adaptive mechanisms which bring about mutual adjustment between vascular growth and local metabolic demand, and genes and growth factors involved in shaping the structure of the coronary tree have only begun to be identified. Fractal and nonlinear dynamic mathematical models generate complex heterogeneous structures from simple nonlinear deterministic rules which are recursively applied. Such nonlinear models may thus help to explain the generation of large vascular trees regulated by synergy of a limited number of genes and signaling molecules. This may explain the relative regularity of space filling of the vascular tree and the asymmetry of branching and flow distribution in the tree.

Synergetic concepts allow to identify emergent coordination phenomena between interacting physiological systems, for example between the cutaneous microcirculation, the sympathetic nervous system and the cardiac and pulmonary systems. The temporal patterns (oscillations of various frequencies) that are found in the data obtained with laser-Doppler anemometers (LDA; e.g. Periflux 2 used in the study) can be investigated by simultaneous recording of photoplethysmographic data obtained in the identical region of interest, as well as in cutaneous regions treated with vasoparalytic procedures which permit to record the dynamics of the arterial system. These strategies were applied to studies in the cutaneous microcirculation (volar side of the index fingers) as well as to mucosal microcirculation (maxillar gingiva) in healthy subjects and in patients suffering from autonomic dysfunction (cutaneous microcirculation) or gingivitis. By this procedure, it could be corroborated that - contrary to popular notions - the temporal fluctuations in the LDA records do not necessarily reflect myogenic vasomotion, but can have multiple causes. In a confirming recent study [Schmid-Schönbein et al., J Auton Nerv Syst, 57, 136-140, 1996], we have demonstrated that the LDA fluctuations under conditions of normal ambient temperature and hand position most likely reflect neurogenic vasoconstriction. Under exceptional conditions, different patterns emerge. Prolonged exposure to ambient temperature (18 degrees C) leads to marked vasoconstriction, with occasional vasodilator escape ('miniature hunting reaction'). Normal subjects under gravitational load and in warm environment (28 degrees C ambient) silence their neurogenetic vasoconstriction reactions, which allows sinusoidal vasomotion to dominate. A similar phenomenon is seen in neuropathic patients at 21-24 degrees C (presumably due to structural defects). Fluctuations in LDA signal taken from the healthy gingiva are entrained to arterial, those taken from inflamed gingiva to respiratory activity. The theory and practice of nonlinear analysis is discussed, and data compression procedures allowing to portray characteristic temporal patterns for future diagnostic procedures are presented.