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Biomedical subjects

U Zwiener

Publications and source records attributed to U Zwiener.

At least 55 records · Page 3Linked to original sources

Exactness of source analysis of biomagnetic signals of epileptiform spikes by the method of spatial filtering: a computer simulation.

On the basis of spatial covariance it is found that, by spatial filtering the localisation of a single dipole source, both parallel and perpendicular to the measurement plane (assuming a signal-noise ratio of 5:1), can be performed with an accuracy of < 0.5 mm. When the signal-noise ratio is increased to 30:1, the resolution of temporally independent current sources separated by 2 mm becomes practicable. This resolution study is carried out by means of a pair of unity current dipoles with the dipole distance as a varying source model parameter. The conclusions, drawn from the results of computer simulation and supported by statistical calculations, refer to the spherical model of the volume conductor of the brain.

Computer Simulation↗

Quantitative analysis of discontinuous EEG in premature and full-term newborns during quiet sleep.

To assess the spatio-temporal structure of discontinuous EEG tracing in mature and immature newborns, we analysed mean spectral power in frequency bands between 0.8 and 16.8 Hz in 6 full-term newborns and 7 premature newborns < 32 weeks of conceptional age. The most striking results showed a significantly higher mean spectral power for the first half of bursts than for the second half recorded in > 2.8-14.8 Hz frequency bands. This pattern was more pronounced in premature than in full-term newborns. No clear differences were observed in comparisons between the first and the second half of the interburst periods. In addition, as far as mid and high frequency band spectra were considered, the mean spectral power of burst was, in both groups, higher in the right as compared to the left occipital regions.

Brain↗

Morphofunctional effects of moderate forebrain ischemia combined with short-term hypoxia in rats--protective effects of Cerebrolysin.

Morphofunctional effects of combined moderate forebrain ischemia due to permanent bilateral carotid artery ligation and short-term systemic hypoxia in rats were investigated. Moreover, a putative effect of brain protection by Cerebrolysin (Cerebrolysin, EBEWE, Austria), a brain tissue hydrolysate containing a mixture of 85% free amino acids and 15% small peptides (MW < 10,000), was studied. Eighty-seven adult Wistar rats (24 Cerebrolysin treated and 63 controls) were subjected to chronic moderate forebrain ischemia by permanent bilateral carotid artery ligation for 7 days. Twenty-four hours after the onset of ischemia, 56 of them underwent an additional hypoxic hypoxia (FiO2 = 0.08) of 15 min. A first group (19 out of 56 animals) received Cerebrolysin (every dose 2.5 ml/kg body weight s.c.) after ligation, after hypoxia and then daily. A second group (6 out of 56 animals) received an equal volume of physiological saline after ligation and Cerebrolysin the first time after hypoxia and then once a day. An untreated control group (31 out 56 animals) received physiological saline. Changes in behavior were scored and electrophysiological activity was quantified by spectral ECoG analysis before carotid artery ligation, before and after hypoxia, and once a day during the following 7 days. On the 7th day after hypoxia, the animals were sacrificed and the grade of histological damage was quantified by morphometry. After permanent carotid artery ligation, 20 out of 63 (31.7%) untreated control animals died within 24 h but only 4 out of 20 (16.7%) Cerebrolysin treated animals. However, Cerebrolysin had not detectable effect on mortality after the additional acute hypoxia. Within 24 h after hypoxia, ECoG power of the higher frequency ranges remained low (p < 0.05). Surviving animals showed a significantly higher ECoG power during and 15 min after hypoxia than those animals that died within 48 h after hypoxia (p < 0.05). All animals showed reduced behavioral activity (p < 0.01) 20 min after hypoxia, however, basal reflex responses were not altered. The major patterns of neuronal damage were coagulation necrosis and general sponginess of the neuropil which is a sign of brain edema. These changes occurred predominantly within the superolateral convexities of the parietal cortex, in the entorhinal and in the piriform cortex as well as in the CA1 and CA4 region and in the dentate gyrus of the hippocampus. The striatum and the origin nuclei of the brain nerves were also affected. We did not observe a relationship between behavior, ECoG depression and the extent of morphological damage after hypoxia nor did we find any protective effects of Cerebrolysin on these parameters. Rather it is suggested that the degree of ECoG depression immediately after hypoxic hypoxia could be a predictor for prognosis of animal survival. Cerebrolysin reduced the amount of early mortality which was caused by moderate global forebrain ischemia. However, no protective influences of the amount of brain tissue damage could be shown.

Amino Acids↗

Physiological effects and brain protection by hypothermia and cerebrolysin after moderate forebrain ischemia in rats.

The "therapeutic window" of neuroprotective intervention due to hypoxic-ischemic brain injuries are initial disturbances of the neuronal function in regions of only moderate decrease of local cerebral blood flow (ICBF). Because of limited effects of single therapeutic principles therapeutic combinations should be tested. Neuroprotective effects of mild hypothermia and the nootropic drug Cerebrolysin (Cerebrolysin, EBEWE, Austria) on ICBF and development of brain edema were used. Four groups of adult Wistar rats (untreated and Cerebrolysin treated animals with 35 degrees C and 37 degrees C rectal temperature) were subjected to moderate forebrain ischemia by permanent bilateral carotid artery ligation for 6 h. The ICBF was measured continuously in the frontal and the occipital cortex by a 2-channel Laser Doppler flowmeter. The ECoG was derived from 4 ECoG leads above the frontal and occipital cortex and quantified by spectral analysis. Six hours after the onset of ischemia, the function of the blood-brain barrier to proteins was determined by staining with Evans Blue, the animals were sacrificed and the brain water content was estimated by gravimetry. Permanent bilateral carotid artery ligation led to an abrupt ICBF reduction to between 40-50% of baseline levels. Within a few minutes, however, the ICBF increased again to 50-80% of the baseline. The reduced spectral band power of the ECoG was correlated with the decreased ICBF values (p < 0.05) that indirectly indicated changes in the energy state of the neurons (p < 0.05). Changes in the ECoG appeared only with a delay of approximately 4 sec after the onset of ICBF reduction. Six hours after the onset of ischemia, a cytotoxic brain edema was shown in the frontoparietal cortex and hippocampus. Reducing the temperature by 2 degrees C diminished the decrease in ICBF between 10 min and 2 h after the onset of ischemia (p < 0.05). This effect was noted in the frontal but not in the occipital cortex. Furthermore, mild hypothermia prevented the loss of ECoG spectral power in the beta, alpha and theta bands (p < 0.05) as well as the development of cytotoxic brain edema. Cerebrolysin prevented the development of brain edema, too, both under normo- and hypothermic conditions. The ICBF was restored to higher levels in the occipital cortex in comparison both to the normothermic Cerebrolysin treated and hypothermic untreated rats (p < 0.05). This effect of Cerebrolysin was associated with only slight changes in ECoG, indicating that the neuronal activity state and the energy supply was obviously not decisively influenced. In conclusion, moderate ICBF reduction in rats to about 50-80% of baseline values was detectable in the ECoG by using spectral analysis. This reduction led to the development of cytotoxic brain edema in rats within 6 h. Thus, hypothermia prevents the development of cytotoxic brain edema. Cerebrolysin enhanced the effects of hypothermia on ICBF reduction and on the development of brain edema.

Amino Acids↗

Changed systemic and cerebral hemodynamics and oxygen supply due to gradual hemorrhagic hypotension induced by an external PID-controller in newborn swine.

An experimental design including an external closed-loop PID-(proportional-integral-differential-)controller is presented which enables the induction of gradual hemorrhagic hypotension at different stages of blood flow reduction up to stages of critically disturbed systemic and regional hemodynamics and oxygen supply. For this purpose nine newborn piglets (12-26 hours old, body weight 1626+/-160 g) were anesthetized and artificially ventilated. Gradual hemorrhagic hypotension was induced at four different steady state stages (stage 1 = 60 mmHg; stage 2 = 50 mmHg; stage 3 = 40 mmHg; stage 4 = 35 mmHg) every 30 minutes by gradual blood withdrawal using external PID controller equipment. Cardiac output and brain regional blood flows were measured by the colored microsphere technique. Systemic and brain regional hemodynamics and O2 supply, metabolic parameters and blood catecholamine concentrations were obtained under baseline conditions and at every 25th minute of the four different steady state stages. About 35 percent of the calculated total blood volume (cTBV) was withdrawn in order to reach the first stage of hemorrhagic hypotension. Further blood withdrawal of about 10 percent of the cTBV, about 5 percent of the cTBV, and about 3 percent of the cTBV were necessary to reach the other respective hypotensive stages. Gradual hemorrhagic hypotension led to an increasing reduction of the cardiac output at every hypotensive stage up to about 20 percent of the baseline value (p<0.05). This was accompanied by a concomitant increase of the total peripheral resistance to about 2.5 fold (p<0.05) and a huge increase in the blood catecholamine concentrations (epinephrine: about 64 fold; norepinephrine: about 35 fold). The induced redistribution of the circulating blood volume was shunted to the vital organs. Therefore, brain cortical blood flow was slightly increased at stage 1 and stage 2. A significant reduction of rCBF did not occur until stage 4 (p<0.05). Regional cerebrovascular resistance was concomitantly reduced at stage 1 and stage 2 (p<0.05) and thereafter again slightly elevated. Brain cortical oxygen consumption was maintained up to stage 2, reduced by about 20% at the next stage of hemorrhagic hypotension (p<0.05) and reached the lowest level of about 50% from baseline at stage 4 (p<0.05). Excellent accuracy and stability was shown at each stage for the external PID controller equipment, so that each given setpoint of the instantaneous mean arterial blood pressure was reached and stabilized even at the lowest hypotensive stage (stage 1: 59.53+/-0.23; stage 2: 50.03+/-0.56; stage 3: 39.18+/-1.75; stage 4: 35.28+/-0.45 mmHg (mean+/-SD)). We conclude that the experimental design presented, with an external PID controller to induce gradual hemorrhagic hypotension in newborn piglets is sufficient for producing functional states with changed systemic and cerebral features with high stability and accuracy, enabling a systematic study of disturbed regional hemodynamics and energy metabolism under steady state conditions even under critically changed states of the systemic cardiovascular regulation.

Animals↗

Adjustment of reduced arterial blood pressure--a tool for investigations into gradually reduced brain function.

Hypoxic-ischemic disorders of the neonatal brain function depend in particular on critical decrease of arterial blood pressure (ABP) below the limited range of cerebral autoregulation. An experimental design including an extracorporal ABP controller is presented which enables the induction of gradual hemorrhagic hypotension at different stages of blood flow reduction up to stages of critically disturbed systemic and regional hemodynamics and oxygen supply. In nine newborn piglets several levels of critically reduced ABP (60, 50, 40, 35 mmHg, normal about 75 mmHg) were stabilized over 30 min, and heart rate, breathing, blood gases, systemic and cerebral hemodynamics, and electrocorticogram were recorded. It was found that the reduced circulating blood volume was redistributed in favour of the vital organs. Therefore, brain cortical blood flow was slightly increased at ABP = 60 and ABP = 50 mmHg. A significant reduction of cortical blood flow occurred only at ABP = 35 mmHg. The experimental design which was based on an extracorporal ABP controller is necessary and sufficient for producing functional states of gradual hemorrhagic hypotension with high stability and accuracy, enabling a systematic study of disturbed regional hemodynamics and disturbed energy metabolism under steady state conditions, even under critically changed states of the systemic cardiovascular regulation.

Animals↗

[Deterministic-chaotic and spectral-functional analysis of heart rate and respiratory movements].

After an introduction into the analysis of periodical-linear and deterministic- chaotic characteristics of heart rate fluctuations and respiratory movements their physiological background and clinical aspects are debated. Using the example of own results at the mature rabbit and new-born pig different relations of periodical-linear and deterministic-chaotic characteristics in dependence on the experimental status and neurovegetative blockades are demonstrated. From the data assignments of these characteristics are derived.

Animals↗

Relations between parameters of spectral power densities and deterministic chaos of heart-rate variability.

To evaluate whether or not heart-rate variations (HRV) have both periodic and deterministic-chaotic properties in conscious and anaesthetized states, HRV of 9 rabbits were analysed by power spectral analysis and methods of deterministic chaos. In order to correlate these properties with the physiological structure of HRV, cholinergic and beta-adrenergic blockades and medullar transections were done. A predominant deterministic-chaotic structure of HRV with high fractal correlation dimension (CD) during conscious state changes to a more periodic structure and lower CD during general anaesthesia. The main periodic and deterministic-chaotic components of HRV are vagally mediated because of their strong reduction by cholinergic blockade, but not by beta-adrenergic blockade or medullar transection.

Animals↗

Colored microsphere technique as a new method for quantitative-multiple estimation of regional hepatic and portal blood flow.

A new method for multiple, quantitative estimation of regional splanchnic blood flow is presented which overcomes all the limitations of the radionuclide microsphere technique. By direct comparison of two methods, i.e., simultaneous blood flow measurement with radionuclide-labeled and colored microspheres, it was shown that the quality of flow measure was quite similar. Simultaneous measurement using paired radionuclide-labeled microspheres yielded an excellent correlation between both values of r = 0.997, a variability of 4.58 +/- 3.84% and a SEE-value of 0.167 ml/g/min. The colored microsphere technique produced corresponding values with r = 0.998, a variability of 5.94 +/- 7.80% and a SEE-value of 0.212 ml/g/min (n.s.). This is also shown for five different abdominal organs and tissues with quite different flow rates under normal physiological conditions. Thus, the colored microsphere technique is a suitable experimental method for making multiple and quantitative measures of the nutritive blood flow through splanchnic organs and tissues and yields values of arterial blood inflow into the liver and into the circulatory bed which is drained by the portal vein.

Animals↗

Characterization of complex heart rate dynamics and their pharmacological disorders by non-linear prediction and special data transformations.

OBJECTIVE: The aim of the presented method was the characterization of different complex heart rate dynamics in conscious rabbits as well as during general anaesthesia and vagal blockade. This was done by non-linear prediction of original measured and special surrogate data in the phase space. METHOD: The development of the prediction error in dependence on the prediction time interval was investigated in the phase space. Two kinds of surrogate data were produced and tested with regard to non-linearities and orientation in the phase space. Typical characteristics of prediction error development were shown for simulated uncorrelated stochastic, correlated stochastic, regular deterministic, and deterministic chaotic signals. These characteristics were used to evaluate the measured heart rate data in connection with tests of surrogate data. RESULTS: It could be shown that heart rate fluctuation cannot be described by one of these ideal models alone. Common consideration of all investigated prediction characteristics indicated chaos in the heart rate of conscious rabbits as well as during anaesthesia and vagal blockade, where non-linear correlated stochastic properties could not be excluded. The different amount of non-linearities and orientation was described quantitatively. CONCLUSIONS: Detailed analysis of prediction error development in the phase space, connected with tests for non-linearities and orientation, enabled a specific quantitative characterization of complex heart rate dynamics and their pharmacological disorders.

Anesthesia, General↗

Deterministic--chaotic and periodic properties of heart rate and arterial pressure fluctuations and their mediation in piglets.

OBJECTIVE: Only the simultaneous analysis of periodic and nonlinear properties of heart rate fluctuations (HRF) can describe completely this complex physiological process. Up to now there is, apart from a study of our own, no systematic and correlative investigation using both parameter groups, also not in early development. Thus, we tried to describe in this manner these properties of HRF, the corresponding mean arterial pressure fluctuations (MAPF) and respiratory movements (RM) and their mutual relations in neonatal pig. METHODS: In 6 term newborn piglets, periodic properties of HRF, RM, and MAPF were analyzed by spectral and coherence analysis, and deterministic-chaotic properties by calculation of correlation dimension (CD), Lyapunov exponent (LE), and construction of phase space plots. The assumption of deterministic chaotic components was supported by Theiler's test for nonlinearity, by always positive leading LEs, and by the results of a nonlinear deterministic model. These analyses were done in sleep states, general anaesthesia, hypoxic hypoxia, in ventilated state, and during cholinergic and additional beta-adrenergic blockade. RESULTS: In all experimental states, HRF and MAPF have periodic and nonlinear, very probably deterministic-chaotic properties, but in different relations. In anaesthetized piglets, periodic properties of HRF and MAPF dominate. In hypoxia the decreasing LE and CD of HRF and CD of MAPF were connected with increasing MAPF power density. Cholinergic blockade caused a decreased overall HRF and MAPF power and a decreasing LE and CD, but beta-adrenergic blockade decreased a small part of power density of both in 0.02-0.08 Hz only. The results of CD, LE, Theiler's test and the low dimensional deterministic model data suggested mainly deterministic-chaotic properties in the nonlinear part of HRF and MAPF. CONCLUSIONS: Already in neonatal piglets, both periodic and nonlinear, very probably deterministic chaotic properties of HRF and MAPF exist which change both during hypoxia and cholinergic blockade. They are partly cholinergically and--to a small extent--also beta-adrenergically mediated. The decrease of nonlinear complexity of HRF and MAPF during hypoxia suggests characteristic pathological change even in early development.

Anesthesia, General↗

Heart rate fluctuations of lower frequencies than the respiratoryrhythm but caused by it.

In conscious adult rabbits, "classical" respiratory sinus arrhythmia does not occur because the respiratory frequency (RF) always exceeds half the heart rate (HR). However, slow HR fluctuations, not synchronous with the respiratory rhythm but affected by it, occur systematically. We have shown that these can be calculated by using aliasing rules. During general anaesthesia, when the RF decreases so that respiratory frequency is less than half the heart rate, classical respiratory sinus arrhythmia occurs and can be greatly reduced by vagal blockade. The slow HR fluctuations which are not synchronous with the respiratory rhythms, but are affected by it are mainly vagally mediated, because vagal blockade virtually eliminates them.

Animals↗

Brain peroxidative and glutathione status after moderate hypoxia in normal weight and intra-uterine growth-restricted newborn piglets.

In order to investigate the pathogenetic factors causing the relatively frequent occurrence of brain injury in intrauterine growth-restricted newborns, lipid peroxidation products (TBAR), glutathione (GSH, GSSG) and in vitro production of reactive oxygen species (chemiluminescence, stimulated lipid peroxidation, H2O2 formation) were studied in the brain of normal weight (NW) and intra-uterine growth-restricted newborn piglets (IUGR) after 1 hour of hypoxia (FiO2 11%) and 90 min reoxygenation. Cardiocirculatory parameters and catecholamine release into the blood were also measured. In the cerebellum, higher GSH content, but also higher in vitro production of lucigenin amplified chemiluminescence were found in comparison to other brain regions, independent of growth restriction and hypoxia. Moderate hypoxia without acidosis and hypercapnia resulted in GSH depletion especially in the brain of IUGR, but no changes in GSSG concentrations were measured. Though TBAR decreased after hypoxia/reoxygenation, in some brain areas of IUGR higher TBAR values were found in comparison to NW. H2O2 formation, stimulated lipid peroxidation and lucigenin and luminol amplified chemiluminescence in the 9000 x/g supernatant of brain tissue did not reveal special response of IUGR to hypoxia/reoxygenation. Hypoxia-induced circulatory centralisation due to increased release of catecholamines into the plasma prevented oxygen deficiency also in the brain of IUGR. The role of brain monoamine metabolism in the production of reactive oxygen species, followed by greater GSH depletion and higher in vivo formation of lipid peroxides in IUGR is discussed.

Animals↗

[Phase portraits of transfer systems--detection of nonlinear transmission properties between respiratory movements and heart rate fluctuations].

A new approach to the analysis of non-linear systems is proposed. It enables the reconstruction of the system state movement in a multi-dimensional phase space. The resulting phase portraits of the system behaviour were characterised quantitatively by estimating the correlation dimensions and prediction errors. This new approach was validated using simulated typical transfer systems. The measured respiratory movements and heart rate fluctuations of rabbits were employed for the first time to investigate the non-linear transfer properties between respiratory activity and heart rate in the system phase portraits. Significant non-linear transfer characteristics between respiratory movements and heart rate fluctuations were found--also during the awake phase--which have so far not been quantified.

Animals↗

Peroxidative status and glutathione content of the brain in normal weight and intra-uterine growth-retarded newborn piglets.

The peroxidative and glutathione status as well as the production of reactive oxygen species were studied in the brain of normal weight (NW) and intra-uterine growth-retarded (IUGR) newborn piglets. In NW as well as IUGR newborn piglets reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxides, iron stimulated lipid peroxidation, H2O2 production and lucigenin and luminol amplified chemiluminescence are very similar in the different brain regions, with one exception. In the cerebellum, higher GSH concentration, higher superoxide anion generation, lower levels of lipid peroxides and a tendency toward a lower capacity of H2O2 production were seen. But the intra-uterine growth retardation to body weights of half the average body weights of the respective litter did not influence the peroxidative status and the GSH/GSSG equilibrium in the brain of newborn piglets.

Animals↗

Computer-assisted neurovegetative monitoring in patients after heart transplantation.

The effects of orthotopic heart transplantation on spontaneous fluctuations of the respiration rate and heart rate were studied with a computer-assisted system for neurovegetative monitoring in 22 patients (mean age +/- SD: 48.7 +/- 9.4 years) 19.5 +/- 14.4 months after transplantation. The control group consisted of 12 healthy volunteers (mean age +/- SD: 38.7 +/- 6.6 years). The mean (+/- SE) respiratory rate was higher in the transplantation group than in the control group (17.7 +/- 0.8/min vs. 14.6 +/- 1.1 breaths/min, P < 0.2). The mean variability of the respiratory rate was smaller in the transplant patients than in the controls (3.7 +/- 0.3 vs. 2.8 +/- 0.4, P < 0.2). The heart rate variability coefficient in the patients after transplantation was lower than that in the controls (1.3 +/- 0.1% vs. 6.9 +/- 0.5%, P < 0.001). Spectral analysis of heart rate variability showed a smaller decrease of variability of respiration (P < 0.05) than of blood pressure regulation (P < 0.001) or of the angiotensin-renin system (P < 0.001). A separate group of 7 transplant patients (mean age 51.0 +/- 7.7 years) had activated cardiac pacemakers and thus no spontaneous physiologic heart rate oscillations. The variability of the respiratory rate in these patients was lower than in the other 22 transplant patients (1.8 +/- 0.2 vs. 3.7 +/- 0.3, P < 0.001). The data provided by multiparametric neurovegetative monitoring support the evaluation of complex regulatory mechanisms of respiratory and cardiovascular function and their adaptability after orthotopic heart transplantation.

Adult↗

Forms of physiological aliasing within the heart rate fluctuations by higher frequent respiratory movements.

In adult conscious rabbits, the respiratory frequency (RF) is almost always higher than half the heart rate (HR) Thus, no "classical" respiratory sinus arrhythmia occurred. But now, slow HR fluctuations, which were not synchronous to the respiratory rhythm but effected by it, occurred systematically. By cholinergic blockade, these slow HR fluctuations could be essentially reduced but not completely abolished. Up to now, this phenomenon was not be taken into account in the analysis of HR fluctuations. Thus misinterpretations are inevitable. During general anaesthesia, the RF decrease up to 2 RF < HR, and now classical respiratory sinus arrhythmia occurred which also could be essentially reduced but not completely abolished by vagal blockade. The possibilities of calculation of such slow HR fluctuations were shown, as those during 1/2 HR < RF < 3/2 HR and RF > 3/2 HR.

Acid-Base Equilibrium↗