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U Zwiener

Publications and source records attributed to U Zwiener.

At least 37 records · Page 2Linked to original sources

Relation between brain tissue pO2 and dopamine synthesis of basal ganglia--a 18FDOPA-PET study in newborn piglets.

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to oxygen deprivation. However, the respective enzyme activities have yet not been measured in the living neonatal brain. In this study, we have used 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine, in the brain of newborn piglets under normoxic and moderate asphyxial conditions. The study was performed on 8 newborn piglets (2-5 days old). In each piglet PET studies were performed under control conditions and during 2-hour asphyxia. Simultaneously, brain tissue pO2 was recorded, cerebral blood flow (CBF) was measured with colored microspheres and cerebral metabolic rate of oxygen (CMRO2) was determined. Asphyxia was induced by lowering the inspired fraction of oxygen from 0.35 to 0.10 and adding about 6% CO2 to the inspired gas. Asphyxia elicited a more than 3-fold increase of the CBF (p < 0.01) so that CMRO2 remained unchanged throughout the asphyxial period. Despite this, brain tissue pO2 was reduced from 19 +/- 4 mm Hg to 6 +/- 3 mm Hg (p < 0.01). Blood-brain transfer of FDOPA as well as permeability-surface area product (PS) from striatum were unchanged. Striatal synthesis rate of fluoro-dopamine from FDOPA (k3) was, however, significantly increased (p < 0.01). This increase of the AADC activity is associated with reduced brain tissue pO2. Asphyxia-induced CBF increase impedes an alteration of brain oxidative metabolism.

Animals↗

Regional distribution of cerebral blood volume and cerebral blood flow in newborn piglets--effect of hypoxia/hypercapnia.

The relationship between regional parenchymal cerebral blood volume (CBV), regional cerebral blood flow (CBF) and the calculated mean transit time (MTT) was investigated in 14 newborn piglets. The effects of combined hypoxic hypoxia (PaO2 = 32 +/- 5 mm Hg) and hypercapnia (paCO2 = 68 +/- 5 mm Hg) were measured in seven animals. Remaining animals served as the control group. During baseline conditions the highest CBF and CVB values were found in the lower brainstem and cerebellum, whereas white matter exhibited the lowest values (p < 0.05). MTT was prolonged within the cerebral cortex (2.34 +/- 0.42 s-1) compared with the thalamic MTT (1.53 +/- 0.38 s-1) (p < 0.05). Under moderate hypoxia/hypercapnia, a CBF increase to the forebrain (p < 0.05) resulted in an elevated brain oxygen delivery (p < 0.05) and so CMRO2 remained unchanged. Moreover, a moderate increase of CBV and a marked shortening of MTT occurred (p < 0.05). The CBV increase was higher in structures with lowest baseline values, i.e., thalamus (66% increase) and white matter (62% increase) (p < 0.05). MTT was between 22% of baseline in the lower brainstem and 49% in white matter (p < 0.05). We conclude that under normoxic and normocapnic conditions the newborn piglets exhibit a comparatively enlarged intraparenchymal CBV. Moderate hypoxia and hypercapnia induced a marked increase in cerebral blood flow which appears to be caused by an increased perfusion velocity, expressed by a strongly reduced mean transit time and by a concomitant CBV increase.

Animals↗

Upregulation of the aromatic amino acid decarboxylase under neonatal asphyxia.

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to asphyxia. However, the respective enzyme activities have not yet been measured in the living neonatal brain. In this study, we have used 18F-labeled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron-emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine (DA), in the brain of newborn piglets. Simultaneously, the cerebral blood flow (CBF) was measured with colored microspheres. Asphyxia elicited an up to threefold increase of the CBF. Despite this, the blood-brain transfer of FDOPA as well as the clearance rate constants from brain were unchanged. However, the synthesis rate of FDA from FDOPA was significantly increased in frontal cortex, striatum, and midbrain. This increase of the AADC activity and the decrease of monoamine oxidase activity may contribute to the increase of extracellular DA during asphyxia which is expected to be involved in severe disturbances of neuronal metabolism, e.g., by generating free radicals.

Algorithms↗

Evaluation of micro tip pressure transducers for the measurement of intracerebral pressure transients induced by fluid percussion.

We describe the application of MIKRO TIP miniature pressure transducers (MPT) for the in vivo measurement of intracerebral stresses induced by traumatic brain injury (TBI). In order to test the linearity of these transducers pressure pulses of different amplitudes (duration approximately 10ms) were generated in a closed calibration chamber. A piezoelectric pressure transducer (PPT) served as the reference measure. A linear correlation was found within the pressure range between 0.57 and 5.09 bar (R2 = 0.998). The frequency transmission characteristics of the MPTs are comparable to the PPT. In three juvenile swines (6 weeks of age) pressures within the brain tissue were induced by fluid percussion (FP) and were measured in the anterior, middle, and posterior cranial cavity as well as in the extracranial part of the medulla oblongata. The data obtained in our experiments agree with the basic biomechanics of FP known from studies in cats and rabbits. Due to their small size, MPTs can be applied in living animals. Stereotaxic positioning of these catheters at any site of the brain and spinal cord requires only minimal surgery. Therefore, MPTs are useful in evaluating animal models of brain injury and in generating input data for computational models of head injury as well as to validate the mathematical results of such models with experimental data.

Animals↗

Ontogenetic aspects of traumatic brain edema--facts and suggestions.

Diffuse brain swelling (DBS) after severe traumatic brain injury (TBI) occurs more commonly in children than adults. Most of the recent clinical studies suggest that young children are more negatively affected by DBS. Until now studies in young animals in which the pathophysiology of DBS was evaluated remained seldom. However, pathogenetic mechanisms of edema formation after TBI in the immature brain appeared to be different in comparison to adult brains. There are evidences that vasogenic as well as cytotoxic edema components may be responsible for the development of DBS. Besides mechanical disturbance, the blood-brain barrier seems to be strongly endangered by oxidative stress after TBI because regional antioxidative capacity is obviously diminished. In addition, cytotoxic components of DBS may be caused by at least two different mechanisms. First, it was shown that a sustained posttraumatic cerebral hypoperfusion occurs in the immature brain. Moreover, a transient increase of NMDA receptor expression at this period of life may be responsible for an increased threat of intracellular sodium ion accumulation in brain cells. Obviously, brain swelling can be detrimental because it can elevate intracranial pressure, impair CBF, and may represent ongoing secondary brain injury.

Animals↗

Hypothermia related changes in electrocortical activity at stepwise increase of intracranial pressure in piglets.

Recent experimental studies have demonstrated that mild hypothermia can be effective in the control of intracranial hypertension. However, investigations to analyze the effects of hypothermia on changes in brain oxygen metabolism and electrocortical activity caused by increased intracranial pressure (ICP) are lacking. We examined the effects of mild hypothermia on electrocorticogram (ECoG) in combination with measurement of regional cerebral blood flow (CBF) and estimation of brain oxygen metabolism during stepwise increase of ICP. For this purpose thirteen female piglets (14 days old, 4-5 kg b.w.) were anaesthetized and mechanically ventilated. An epidural balloon was gradually inflated in order to increase ICP to 25 mmHg, 35 mmHg and 45 mmHg every 30 minutes at adjusted mean arterial blood pressures (MAP). This procedure resulted in gradual cerebral perfusion pressure (CPP) reduction of about 70%, 50%, and 30% of baseline [baseline CPP: normothermia (NT) 80+/-3 mmHg; hypothermia (HT) 84+/-3 mmHg]. Control animals were maintained in a normothermic state (38.6+/-0.2 degrees C). HT animals were surface cooled and maintained at 31.9+/-0.1 degrees C. ECoG, regional CBF, cerebral oxygen delivery (cDO2) and the cerebral metabolic rate of oxygen (CMRO2) were estimated during the normothermic period, after hypothermic stabilization, and after the gradual CPP reductions. The baseline ECoG showed the typical delta-dominated frequency pattern for isoflurane anaesthesia. At the hypothermic level, a frequency shift was seen from delta activity towards the higher frequencies (theta- and alpha activity) and the total spectral power was significantly reduced (56+/-17% from baseline, p < 0.05). the cortical CBF decreased markedly to 67+/-10% (p < 0.05), whereas the medulla oblongata blood flow increased slightly. During controlled increase of ICP by regional mass expansion from epidural balloon inflation, we found at mild and moderate stages of ICP increase (25 and 35 mmHg) only minimal changes in the ECoG in hypothermic animals compared to the hypothermic baseline, whereas the ECoG in normothermic animals showed a marked decrease in frequency, amplitude and total spectral power. We conclude that mild hypothermia produces an arousal-like ECoG activity with marked frequency shift to alpha activity and a change from high to low voltage activity. Furthermore, the hypothermic brain showed a preserved neuronal function at moderate stages of ICP. Obviously, hypothermia improves the functional tolerance of the brain to impaired oxygen supply.

Animals↗

A piglet model for evaluation of cerebral blood flow and brain oxidative metabolism during gradual cerebral perfusion pressure decrease.

A piglet model was developed to study the effect of epidural volume expansion on cerebral perfusion pressure (CPP) by stepwise elevating intracranial pressure (ICP). Mean arterial blood pressure (ABP) was strictly maintained using an extracorporeal ABP controller. Two-week-old piglets (n = 10) were studied by surgically placing an epidural balloon over the right parietal region and gradually increasing the inflation to increase ICP to 25, 35 and 45 mm Hg, maintaining each pressure level for 30 min. Regional cerebral blood flow was measured using the colored microsphere technique, and cerebral oxygen delivery and cerebral metabolic rate of oxygen were calculated at baseline conditions and after reaching ICP levels of 25, 35 and 45 mm Hg. The results showed that this model of epidural volume expansion reproducibly reduces CPP to 70, 50 and 33% of baseline CPP values with elevation of ICP, and that the physiological variables remained stable throughout each increase in ICP. We conclude that the model simulates the effects of an acute intracranial focal mass expansion and is well suited for the evaluation of different therapeutical strategies for increased ICP in newborns and infants.

Animals↗

Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats.

The effects of brain-derived peptides (BDP; Cerebrolysin) upon the amount of brain injury due to focal brain ischemia were assessed. Male Thomae rats were divided randomly into a sham-operated group (n = 5), an ischemic control (untreated) group (n = 7) and an ischemic BDP-treated group (n = 6) and subjected to reversible middle cerebral artery occlusion (MCAO) for 2h followed by 90min of reperfusion. Local cortical blood flow (LCBF) was monitored by Laser-Doppler flowmetry to assess the MCAO and to measure the blood flow in regions peripheral to the infarction. Infarcted areas of the hippocampus and subcortical structures were quantified in hematoxylin and eosin (H&E) stainings. Functional disturbances of the neurons were detected by immunohistochemical staining of the microtubule associated protein MAP2. Moreover, brain edema was estimated morphometrically. LCBF was estimated from the periphery of infarcted areas and was reduced to 55 to 65% of baseline values (p < 0.05). Reperfusion led to LCBF being increased again to baseline values. No differences in LCBF between the control and the BDP-treated animals were found. In the hippocampus, BDP-treated animals showed a significant reduction of loss of MAP2 immunoreactivity in the subiculum and CA1 region by 59% and 64%, respectively, in comparison to control animals (p < 0.05). The amount of irreversibly damaged neurons in these regions was decreased in tendency. However, the inner blade of the dentate gyrus in BDP-treated animals showed a significant reduction of neuronal injury by 98% (p < 0.05). Likewise, BDP treatment reduced the size of the areas showing a loss of MAP2 immunoreactivity in the thalamic and hypothalamic structures by 51% and in the mesencephalon by 81% (p < 0.05). The size of the infarcted areas in these regions (H&E) was reduced in tendency. In the caudate putamen, no protective effect of BDP-treatment could be proven. Cerebral infarction was accompanied by an increase in the volume of the ischemic hemisphere by 10 +/- 1% in the control and 8 +/- 1% in the BDP-treated animals. These findings indicate a beneficial effect for BDP treatment in ameliorating the early effects of focal brain ischemia.

Amino Acids↗

Simultaneous measurement of [18F]FDOPA metabolism and cerebral blood flow in newborn piglets.

Available information on the dopamine (DA) metabolism of the immature brain is rare. In order to establish a useful animal model we have performed PET experiments in anesthetized neonatal pigs using 6-[18F]-fluoro-L-DOPA (FDOPA) as tracer. In this study, we have simultaneously determined the cerebral blood flow and the rate constant of FDOPA conversion by the aromatic amino acid decarboxylase, the ultimate enzyme in the synthesis of dopamine. The estimated values of FDOPA decarboxylation in the basal ganglia were similar to values calculated in adult animals and humans. However, in contrast to those studies a significant decarboxylation was also found in the frontal cortex and the cerebellum. HPLC analysis of brain samples also revealed extensive and rapid metabolism of FDOPA in the five investigated brain regions. At 8 min after tracer injection about 80% of FDOPA was already converted to FDA and its metabolites. Surprisingly, a rather high fraction (16-21%) of [18F]-fluoro-3-methoxytyramine was found which may indicate a low storage capacity of vesicular DA at this perinatal stage. It is suggested that the findings are related to the ontogenetic development of the dopaminergic system. The knowledge of the regulation of the DA metabolism in the immature brain may have implications for the understanding of neurodevelopmental effects of perinatal oxygen deprivation.

Animals↗

Cardiovascular function and brain metabolites in normal weight and intrauterine growth restricted newborn piglets--effect of mild hypoxia.

In order to clarify the influence of intrauterine growth restriction on systemic hemodynamics, catecholamine response, and regional distribution of brain energy metabolites per se and during mild hypoxic episodes a study was performed in thirty newborns with a well-characterized state of intrauterine and intra-natal development. Thirty animals were divided into fifteen normal weight piglets (NW) and fifteen intrauterine growth restricted (IUGR) piglets according to their birth weight. Category "NW" covered animals with a birth weight of > 40th percentile; IUGR category covered animals with a birth weight of > 5th and < 10th percentiles. Animals were anesthetized with halothane in 70% nitrous oxide and 30% oxygen and after immobilization artificially ventilated. The acid-base balance and blood gas values at baseline conditions were similar within the different groups investigated and consistent with other data obtained from anesthetized and artificially ventilated newborn piglets. Mild hypoxic hypoxia which was induced by lowering the FiO2 from 0.35 to 0.15 resulted in reduced arterial pO2 (NW: from 115 +/- 37 mmHg to 39 +/- 7 mmHg; IUGR: from 117 +/- 23 mmHg to 39 +/- 3 mmHg; p < 0.05), but arterial pH and pCO2 remained unchanged. Under baseline conditions arterial blood pressure, cardiac output, and myocardial contractility, expressed as dp/dt(max) and plasma catecholamine values were similar in all groups studied. Heart rate was slightly increased in IUGR (p < 0.05). Mild hypoxia led to a strong increase of myocardial contractility in NW as well as IUGR piglets to 2.4 and 2.7 fold and remained increased during recovery (p < 0.05). Moreover, total peripheral resistance was enhanced at the end of recovery period in IUGR animals (p < 0.05). There was a significant increase of epinephrine (E) in NW animals in comparison to sham-operated animals (p < 0.05). Interestingly, during reoxygenation the further increase in E and norepinephrine (NE) levels were enhanced in the animals which suffered from mild hypoxia (p < 0.05). Regional distribution of brain tissue metabolites was partly affected by intrauterine growth restriction. In particular, brain tissue glucose content was strongly reduced by 65 to 72 per cent in all brain regions investigated. Mild hypoxia led to an increase of about 30 percent in NW animals (p < 0.05). In IUGR piglets the percentage increase of brain glucose content was on an average more pronounced but with considerably higher variance. Also, a strong increase of brain lactate content appeared here (p < 0.05). In contrast, brain tissue ATP was quite similar in all groups studied, but brain creatine phosphate was significantly reduced in some forebrain structures of IUGR piglets after mild hypoxia (figure 2, p < 0.05). In summary, this investigation provides information on cardiovascular functions and brain metabolites of normal weight and naturally occurring growth restricted newborn piglets. Mild hypoxemia was well-tolerated from both animal groups. It is suggested that lactate may play a significant role as a source for brain energy production in the newborn IUGR piglets.

Animals↗

Influence of hypoxia and hypoxia/hypercapnia upon brain and blood peroxidative and glutathione status in normal weight and growth-restricted newborn piglets.

Glutathione (reduced (GSH) and oxidized (GSSG)), lipid peroxidation products (TBAR) and in vitro production of reactive oxygen species (ROS, by means of stimulated lipid peroxidation, H2O2 formation and amplified chemiluminescence (CL) in 9000 xg brain supernatants) were studied in the cerebellum (C) and temporoparietal area (TP) of the brain of normal weight (NW) and spontaneously intra-uterine growth-restricted newborn piglets (IUGR) after 1 hour hypoxia (fractional inspired oxygen concentration (FiO2) 8%), and in combination with 10% CO2, followed by 3 hours recovery (FiO2 30%). The strong GSH depletion accompanied by an increased concentration of GSSG and TBAR, more distinct in IUGR, is the most important result in the brain after hypoxia and reoxygenation. Hypercapnia-related acidosis seems to protect the brain of IUGR from hypoxia/reoxygenation induced injury by reducing GSH depletion as well as GSSG and TBAR increases. But stimulated lipid peroxidation and H2O2 formation in 9000 xg supernatants of C and TP were found to be higher in acidosis and hypercapnia. Decreased or unchanged amplified CL, demonstrating lower in vitro production of ROS, cannot explain the GSH depletion after hypoxia and reoxygenation. The scarce changes in erythrocyte GSH and GSSG as well as plasma TBAR concentrations did not reflect the findings in the brain. Nevertheless, the changes in the brain support the hypothesis that oxidative stress plays a role in neuronal damage after hypoxic stress, but the brain of IUGR did not reveal a special response to moderate hypoxia.

Acid-Base Equilibrium↗

Body weight distribution and organ size in newborn swine (sus scrofa domestica) -- a study describing an animal model for asymmetrical intrauterine growth retardation.

Normal growth is the expression of the genetic potential to growth which is neither abnormally constrained nor promoted by internal or external factors. Restricted fetal growth is common in human pregnancy and is associated with increased perinatal morbidity and mortality. Because of ethical restrictions, pathogenetical studies are necessarily dependent on appropriate animal models. In the studies presented, evidence will be provided that the naturally occurring distribution of body weight in newborn piglets, obtained from n = 512 newborn piglets (about 12 hours old) in 50 consecutive deliveries in the breed cohort of the mixed German domestic breed - "Deutsches Land-/Edelschwein" gives an appropriate sampling for providing a statistically reliable basis with which to determine different degrees of fetal growth for further pathophysiological studies intended. A strong inverse correlation (r = -0.66, p < 0.05) was found between the mean weight of the litter and the number of piglets per litter, and an inverse correlation (r = -0.64, p < 0.05) was found between the lowest weight of the littermate and the number of piglets per litter. Moreover, gravimetric investigations were made into an additional 53 one-day-old newborn piglets reflecting the naturally occurring birth weight distribution determined. A marked linear correlation between body weights and various organ weights was found (values of the correlation coefficient amounted to between 0.45 and 0.98; p < 0.05). The lowest variation of organ weights was found in the CNS structures (0.68-1.33). Skeleton and heart exhibited similar ranges of weight variation (0.35-1.81 and 0.38-2.00 of the means) to body weight (0.38-1.77 of the means). This was also expressed in the regression analysis, because the slope values were 0.99 and 0.97 respectively. The hormonal glands investigated, the kidneys, and the abdominal parenchymal organs exhibited the largest ranges of weight variation. Moreover, regression analysis gives evidence that the weight restriction was more pronounced than expected concerning respective body weight. This is indicated by slope values > 1 in almost all of those organs. Plasma concentration of IGF-1 showed an inverse correlation with body weight (r = -0.42; p < 0.05, fig 4). IGF-1 concentration of intrauterine growth retarded (IUGR) newborn piglets was in the mean nearly double that of normal weight animals (p < 0.05) and the brain weight to liver weight ratio was increased more than 2.5 times in IUGR newborn (fig 5 A, p < 0.05). This investigation provides information on the naturally occurring body weight distribution of one-day-old piglets, which was obviously a result of epigenetic factors. Gravimetrical estimation showed clearly that body weight variety is most probably caused by alterations of placental functioning. Severe alterations resulted in asymmetrical growth retardation, which was proved by a significantly increased brain to liver ratio in animals with a body weight < 10th centile. Thus, evidence is provided that naturally occurring asymmetrical intrauterine growth restricted newborn piglets can be identified simply by body weight measurement, so that convenient conditions are given for pathogenetically motivated studies on intrauterine compromised newborns.

Animals↗

Quantitative topographical analysis of EEG during nonstandardized and standardized hyperventilation.

The aim of this study was to compare the topographical quantitative EEG (qEEG) changes induced by nonstandardized hyperventilation and those induced by standardized hyperventilation (with the end-tidal PCO2 being maintained at 2 kPa [15 mm Hg]). We examined 18 healthy volunteers during nonstandardized and 20 during standardized hyperventilation. During nonstandardized hyperventilation, the mean spectral power density in this group significantly increased 1.9 fold within the delta-, 2.2 fold within the theta-, 1.8 fold within the alpha-, and 1.9 fold within the beta-frequency band. There was no significant change of the power ratio and was no topographic difference between 4 frequency bands investigated. During standardized hyperventilation, the mean spectral power density in the group significantly increased to 12.9 fold within the delta-, to 7.6 fold within the theta-, to 1.4 fold within the alpha-, and to 2.4 fold within the beta frequency band. The power ratio decreased significantly. Such a pronounced EEG slowing with delta and theta augmentation was never found during nonstandardized hyperventilation. We conclude that a consistent slowing of the qEEG in all leads including a constant topographical maximum can only be induced by standardized, sufficiently pronounced hyperventilation.

Adult↗

Estimation of nonlinear couplings on the basis of complexity and predictability--a new method applied to cardiorespiratory coordination.

Nonlinear coordination is an essential property of the complex functioning of the autonomic nervous system. Therefore, the coupled behavior of heart rate fluctuations (HRF) and respiratory movements (RM) was analyzed on the basis of their joint reconstruction in the phase space. Independence measures of complexity and predictability were approximated from the correlation integrals which enabled the strength of cardiorespiratory couplings to be quantified. These measures were validated in a simulation study of two coupled nonlinear oscillators in dependence on their coupling strength and respective synchronization effects. The cardiorespiratory coordination during quiet sleep and active sleep of newborn piglets was quantified by means of the proposed independence measures of complexity and predictability. The difference of those measures between the sleep states investigated was more significant than the difference of the respective linear coherence peaks.

Animals↗

Mild hypothermia prevents the occurrence of cytotoxic brain edema in rats.

Hypothermia maintains the impermeability of the blood-brain barrier to proteins and, therefore, presumably the development of vasogenic brain edema after brain ischemia. We intended to determine whether mild hypothermia would have a protective effect against cytotoxic brain edema, the early stage of ischemic brain edema. Two groups of Wistar rats (37 degrees C and 35 degrees C body temperature) were subjected to 6 h of moderate decrease of cerebral blood flow (CBF) by means of permanent bilateral carotid artery ligation, and compared to a third group of unaffected animals. Carotid artery ligation induced a local cerebral blood flow (LCBF) reduction to 50-80% of baseline values. LCBF in the frontal cortex was restored to a higher level in hypothermic animals than in normothermic ones (P < 0.05). In normothermic animals, an increase of brain water content was detected in the frontoparietal and occipital cortex as well as in the hippocampus (P < 0.05), but only in one region of the frontoparietal cortex in hypothermic animals. The impermeability of the blood-brain barrier to proteins was shown by the absence of staining with Evans blue as an indicator of vasogenic brain edema. We conclude that mild hypothermia offers protection against the development of cytotoxic brain edema.

Animals↗

The distribution of normal brain water content in Wistar rats and its increase due to ischemia.

The aim of this study was to describe the normal distribution of the water content in several regions of the rat brain and furthermore to determine if global ischemia results in a variable increase in water content in these regions. Water content was determined in 40 regions; in 8 unaffected brains by gravimetry and in 9 unaffected brains by estimation of the wet/dry weight ratio. In addition, 6 rats underwent 6 h of moderate global brain ischemia in order to evaluate the sensitivity of the investigated brain areas to develop a cytotoxic brain edema. The impermeability of the blood-brain barrier to proteins was evaluated by staining with Evans blue. Physiological differences in water content between the several brain regions ranged from 72.57 +/- 0.77% (mean +/- S.D.) in the medulla oblongata to 84.83 +/- 0.52% in the hypothalamus. Generally, the water content of the grey matter was higher than that of the white matter and increased from the frontal to the occipital and from the parietal to the basal cortex. Even adjacent cortical regions showed differences in the amount of brain water of up to 3.41%. In the ischemic animals, the impermeability of the blood-brain barrier to proteins was not compromised, but an increase in the amount of brain water was found in the frontoparietal cortex of 1.17 +/- 0.37% and hippocampus of 1.49 +/- 0.39% (P < 0.05). This ischemic increase in the brain water content was small in comparison to the normal variance in regional brain water content. Similar results were obtained by determining the wet/dry weight ratio and by gravimetry. Gravimetry led to more consistent results. In conclusion, the study shows great differences in normal water content between the several brain areas in comparison to an only slight increase of water content due to the development of cytotoxic brain edema. The determination of an early state of an increased brain water content requires an adequate and differentiated measurement of different brain areas. The gravimetry fulfills this demand.

Animals↗

Validation of the multiple colored microsphere technique for regional blood flow measurements in newborn piglets.

The use of multiple colored microspheres (CMS) for the measurement of regional blood flow (RBF) in almost all organs and tissues of newborn piglets was validated. For this purpose mixtures of different CMS and/or radio-labeled microspheres (RMS) were injected into the left ventricle of eight newborn piglets. Regional blood flows (RBF) were quantified using the reference sample method. Flow rates estimated by RMS and CMS were compared for each tissue sample. An excellent correlation (r = 0.995-0.999) between CMS and RMS flow rates was found even for organs with low perfusion and tissue samples containing 400-750 CMS. We conclude that the CMS technique is a valid alternative for RBF measurement in newborn piglets, and that all disadvantages arising from radioactive labeling are thereby avoided.

Animals↗

Practical problems of determining the dimensions of heart rate data.

The practical problems are explored of determining the dimension of the phase space set generated from real, experimental and simulated data of the times between consecutive heartbeats in normal and diseased rabbits. It is determined how different measures of dimension have depended on the procedures used to construct the phase space set and on such properties of the data as the amount of data, noise, long-term trends and stationarity. Reproducible estimates of the dimensions of different physiological states are found to require considerable amounts of data recorded under stationary conditions.

Anesthesia, General↗