Biomedical subjects

W Kuschinsky

Publications and source records attributed to W Kuschinsky.

At least 73 records · Page 4Linked to original sources

PubMed1993

Changes in brain capillary diameter during hypocapnia and hypercapnia.

Since changes in the surface area of capillaries may be relevant to capillary exchange, the distensibility of brain capillaries was investigated. Brain capillary diameters were measured after perfusion fixation of brain tissue at a constant perfusion pressure during hypo- or hypercapnia. Sections were embedded, stained, and analyzed by light microscopy. The results showed significant differences in mean capillary diameter between the hypocapnic and the hypercapnic group. In the eight brain structures analyzed, capillary diameters were always larger in the hypercapnic group. Mean capillary diameter was 4.93 +/- 0.29 microns in the hypocapnic group and 5.91 +/- 0.10 microns in the hypercapnic group (means +/- SD). We conclude that brain capillaries exhibit a moderate degree of distensibility. Variations in the precapillary pressure of microvessels may therefore influence both capillary flow and capillary surface area.

Animals↗

PubMed1993

Capillary perfusion during incomplete forebrain ischemia and reperfusion in rat brain.

Previous studies have shown a complete plasma perfusion of all capillaries in the rat brain under normal physiological conditions. This raises the question under which experimental conditions nonperfused capillaries may show up in the brain. Two experimental models were investigated in rats. 1) Reduced cerebral blood flow (CBF) during incomplete forebrain ischemia: hemorrhagic hypotension was maintained for 30 min at a mean arterial blood pressure of 41 mmHg. During the final 5 min of hypotension both carotid arteries were ligated. 2) Reperfusion after incomplete forebrain ischemia: reperfusion lasted for 4 h after either 15 or 30 min of incomplete forebrain ischemia. Under both experimental conditions, the density of the existing as well as the plasma-perfused brain capillary network was quantified using fluorescent double staining. Local CBF was measured during incomplete forebrain ischemia using the quantitative autoradiographic 4-iodo-[N-methyl-14C]antipyrine technique. The results showed a decrease in CBF during incomplete forebrain ischemia, which amounted up to 94%. Whereas normotensive control animals showed a complete staining of all capillaries within 5 s after the intravenous injection of Evans blue, this period of time was increased to 10 s during incomplete forebrain ischemia, indicating a delayed capillary perfusion. Four hours of reperfusion after 15 min of incomplete forebrain ischemia resulted in a complete capillary staining, whereas reperfusion after 30 min of ischemia was followed by intracerebral bleedings and a few nonperfused capillary areas (circulation time of Evans blue: 10 s).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Local cerebral blood flow and glucose utilization after blood exchange with a hemoglobin-based O2 carrier in conscious rats.

The effects of a blood exchange on cerebral blood flow and glucose utilization were studied. A near to total blood exchange (hematocrit < 3%) was achieved in conscious rats by isovolemic hemodilution. Ultrapurified, polymerized, bovine hemoglobin (UPBHB) served as a blood substitute. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 34 brain structures of conscious rats by means of the ido[14C]antipyrine and the 2-[14C]-deoxy-D-glucose methods. A group of rats without blood exchange served as control. After blood exchange LCBF increased from 36 to 126% in the different brain structures resulting in a nearly doubled mean cerebral blood flow (+82%). LCGU increased only moderately by 0-24%. Significant increases in LCGU were observed in 16 brain structures. Mean cerebral glucose utilization slightly increased (+14%). The relationship between LCGU and LCBF was found to be tight both in the control group (r = 0.95) as well as after blood replacement (r = 0.94), although it was reset to a higher overall LCBF-to-LCGU ratio. The profound increases in LCBF observed after blood exchange, which were not paralleled by comparable increases in LCGU, might be explained by a reduction of blood viscosity after blood exchange. Additional effects of blood exchange observed in the present study were an increase of mean arterial blood pressure and a decline of heart rate. The results indicate that replacement of blood with the hemoglobin-based oxygen carrier UPBHB appears to meet the cerebral circulatory and metabolic demands of the brain tissue.

Animals↗

PubMed1993

[Modified hemoglobin as a blood substitute in a rat model].

The use of modified haemoglobin solutions as blood substitutes has been investigated extensively during the past decades. Ultrapurified, polymerised bovine haemoglobin (upbHb) is a promising new substance in this respect. It was the aim of the present investigation to study the cardiovascular and respiratory effects of massive blood replacement with upbHb in a new model of conscious rats with continuous haemodynamic monitoring. METHODS. The right femoral artery and vein of 13 male Sprague-Dawley rats were catheterised during halothane-N2O-O2 anaesthesia. A thermistor catheter was placed in the descending aorta via the left femoral artery for measuring cardiac output by the thermodilution method. After recovery from anaesthesia blood replacement was achieved by arterial blood withdrawal and simultaneous venous infusion of upbHb in equal amounts. The haematocrit was lowered to < 3% and the animals were then left undisturbed in a rat restrainer while breathing room air. RESULTS. The animals showed no signs of disturbed behaviour patterns, distress, or adverse reactions. There were no significant changes in cardiac index and oxygen delivery during the investigation period of 4 h. A marked increase in mean arterial pressure (MABP) and systemic vascular resistance (SVR) of 30% was observed while stroke volume remained unchanged. Blood gases, acid-base status, and plasma glucose showed no major changes. Plasma oncotic pressure increased during the investigation period. CONCLUSIONS. The results indicate that there is adequate oxygenation and sufficient systemic oxygen delivery in conscious and drug-free rats after isovolaemic haemodilution with upbHb to a final haematocrit of < 3%. In contrast to previous haemodilution studies, which have tested non-oxygen-carrying solutions, no changes in cardiac index were observed. The cause of the increase in MAP and SVR remains to be established.

Animals↗

PubMed1993

Changes in local cerebral glucose utilization in the awake rat during acute and chronic administration of ethanol.

Local cerebral glucose utilization (LCGU) was measured in 51 structures of the rat brain after acute and/or chronic oral administration of ethanol using the quantitative autoradiographic 2-deoxyglucose method. In the acute experiments, ethanol (3.2 g/kg) was administered via a gastric tube 110 min before the 2-deoxy-D-[1-14C]glucose. The chronic pretreatment was performed using increasing concentrations of ethanol in the drinking water for a period of 20-24 days. The most striking effects on LCGU were seen in the inferior colliculus. Acute and acute plus chronic treatment with ethanol significantly decreased LCGU by 33% and 37%, respectively, whereas chronic treatment significantly increased LCGU by 25%. In general, acute administration of ethanol decreased LCGU in 16 brain structures, particularly of the auditory system. Chronic treatment, besides its effect on the inferior colliculus, only decreased LCGU in the internal capsule. Chronic plus acute administration of ethanol decreased LCGU significantly in 22 structures. It is concluded that an acute oral administration of ethanol has distinct and mainly depressive effects on the functional activity of several brain areas. Chronic administration is less effective.

Administration, Oral↗

PubMed1992

Fluorescence labeling of the capillary network in rat brains.

To assess the reliability of fluorescence methods for a quantitative staining of brain capillaries, three different immunohistochemical fluorescent markers were used in the rat brain. Staining of the basement membrane by antibodies directed against fibronectin was compared, in the same brain section, with simultaneous staining of the vascular endothelium constituents nonmuscle myosin or von Willebrand factor (factor VIII). These stainings all resulted in identical patterns, which demonstrates their suitability for capillary staining in the brain. It has been claimed that fixation of the tissue results in the appearance of spurious capillary spots. Such a fixation artifact could be excluded using nonmuscle myosin staining. These results validate the methods of quantitative fluorescent microscopical staining of capillary morphology in the brain and therefore support our concept of a continuous perfusion of all capillaries in the brains of conscious rats.

Acetone↗

PubMed1992

Capillary circulation in the brain.

A close relationship exists between the local capillary density in different brain structures and their local blood flow and metabolism. Capillary density appears to have developed depending on local functional demands. Investigation of single capillary perfusion has shown that all capillaries are perfused with plasma in the brain at any time point. Theories of capillary cycling and capillary recruitment have been based on experimental artifacts. Indirect evidence exists for a heterogeneity of perfusion under normal conditions, especially with respect to erythrocyte flow. The capillary diffusion capacity depends on, among other things, the available capillary surface area, which would increase with recruitment of capillaries. In the case of capillary perfusion heterogeneity, the capillary diffusion capacity may also be increased by homogenization of the perfusion rate (slowly perfused capillaries becoming faster perfused). This could give a physiological impression of an "apparent" increase in the capillary surface area. It is recommended that the terms "capillary cycling" and "recruitment" should be used in conjunction with more specific explanations, like "recruitment of erythrocytes" and "recruitment of previously nonperfused capillaries".

Animals↗

PubMed1991

Effects of nicotine withdrawal on the local cerebral glucose utilization in conscious rats.

Chronic infusion of nicotine has been shown to result (1) in an increase in nicotine binding sites in the brain and (2) in a distinct pattern of increases in local cerebral metabolic rate for glucose (CMRglc). The present study addresses two questions: (1) whether a one-day withdrawal of nicotine after a two-week exposure is long enough to restore local CMRglc to the preinfusion values and (2) whether an acute nicotine infusion after one day's withdrawal would influence local CMRglc. Chronic infusion of L-nicotine (12.5 micrograms/kg/min) was performed by osmotic minipumps. Local CMRglc was measured using the quantitative 2-deoxyglucose method in conscious rats. The following results were obtained: (1) a one-day withdrawal of nicotine after a two-week chronic infusion restores local CMRglc to a pattern which is close to the control pattern obtained without any nicotine infusion, and (2) an acute infusion of nicotine after a one-day withdrawal of a chronic nicotine infusion induces distinct increases in local CMRglc of several brain structures; these are essentially identical with structures which are activated during an acute nicotine infusion in otherwise untreated rats (no chronic infusion). The data indicate: (1) The main effects of chronic nicotine infusion on local CMRglc have disappeared after one day of nicotine withdrawal. (2) An acute load of nicotine in such nicotine-withdrawal rats has effects on local CMRglc which resemble those found in previously untreated rats during an acute nicotine infusion. (3) In contrast to most binding studies which have shown persisting increases in nicotine binding sites after one day's withdrawal of chronic nicotine, local CMRglc is restored to control values and can be again activated by an acute nicotine infusion.

Animals↗

PubMed1991

The influence of nicotine on local cerebral blood flow in rats.

Local cerebral blood flow (LCBF) was measured in conscious rats during an acute nicotine infusion. LCBF was measured using the autoradiographic iodoantipyrine method. LCBF was unchanged in most brain structures during nicotine infusion compared to controls. Significant (P less than 0.05) increases were found in 3 structures (lateral geniculate body, superior colliculus, anteroventral nucleus of the thalamus). These structures have already shown increases in local glucose utilization in a previous study [2]. The observed increases in LCBF are interpreted to be secondary to metabolic activation by nicotine indicating the lack of a direct action of nicotine on cerebral blood vessels.

Animals↗

PubMed1991

Coupling of function, metabolism, and blood flow in the brain.

Functional activity, metabolism and blood flow are locally heterogeneous in the brain, but tightly coupled. This adjustment occurs in two different ways: 1. Short-term, dynamic coupling mediated by local vasoactive factors that ensure second-to-second regulation. 2. Long-term, static coupling apparently mediated by capillary density and developed in response to local functional and metabolic activity. Recognizing these two mechanisms permits one to distinguish apparent from real uncoupling. It allows the conclusion that there is no indication of an uncoupling of metabolism and blood flow during physiological conditions.

Animals↗

PubMed1991

Regional density of perfused capillaries and cerebral blood flow in untreated short-term and long-term streptozotocin diabetes.

The regional density of perfused cerebral capillaries (rDPC) and regional cerebral blood flow (rCBF) were measured in 12 selected brain regions in rats after 3 and 20 weeks of streptozotocin-induced diabetes and in control groups. After 3 weeks of diabetes, both rCBF and rDPC were unchanged in the diabetic group compared to the control group. A diabetes duration of 20 weeks causing bilateral cataracts induced a significant (p less than 0.05) reduction in rCBF in two structures in the visual system compared to the control group (visual cortex: 105 versus 129 ml 100 g-1 min-1; lateral geniculate body: 106 versus 128 ml 100 g-1 min-1) and in the pontine reticular nucleus (82 versus 128 ml 100 g min-1), whereas rDPC remained unchanged. A highly significant correlation between rCBF and rDPC was found in both control groups (r = 0.8, p less than 0.005) whereas the correlation was more scattered in the diabetic groups (r = 0.6, p less than 0.05). The present results show that during chronic diabetes, a reduction of rCBF does not affect the number of perfused capillaries.

Animals↗

PubMed1991

Dynamics of capillary perfusion in the brain.

The present study investigates the question of capillary recruitment and reserve capillaries in the brains of awake rats. Perfused capillaries were marked by intravenous globulin-coupled fluorescein isothiocyanate (FITC) and cerebral blood flow was measured autoradiographically. During hypercapnia, the density of perfused capillaries was unchanged compared to normocapnia, although blood flow was markedly increased. This shows the lack of capillary recruitment in the brain during the high flow that occurs during hypercapnia. In additional studies using fluorescent staining both of morphologically existing and of perfused capillaries, perfusion of all capillaries during normal, normocapnic conditions was found. These experiments show the lack of any capillary reserve in the rat brain.

Animals↗

PubMed1991

Physiology of cerebral blood flow and metabolism.

At a normal blood flow and oxygen consumption, the brain uses exclusively glucose as metabolic substrate. Coupling between blood flow and metabolism takes place on a local level. This adjustment occurs in two different ways: 1. Short-term, dynamic coupling mediated by local vasoactive factors that ensure second-to-second regulation. Such reactions appear to be partly dependent on the vascular endothelium. 2. Long-term, static coupling apparently mediated by capillary density and developed in response to local functional and metabolic activity. Recognizing these two mechanisms permits the distinction of apparent uncoupling during physiological conditions from real uncoupling during brain ischemia.

Animals↗

PubMed1990

Glucose utilization, blood flow and capillary density in the ventrolateral medulla of the rat.

A specific population of neurons in the ventrolateral medulla (VLM) acts as the main integration center for the regulation of the sympathetic outflow to the cardiovascular system. In order to investigate whether this nucleus can be distinguished from its surroundings in the reticular formation of the medulla with respect to functional and morphological variables, the present study investigates several of such variables in this area on a quantitative basis. Local medullary glucose utilization was measured by the 2-[14C]deoxyglucose method; local medullary blood flow was quantified using iodo[14C]-antipyrine, and the local density of perfused capillaries was calculated by counting the number of intravascular fluorescent spots in brain sections after i.v. infusion of a globulin-coupled fluorescent dye. The values obtained from the VLM were compared with the respective values found in a reference area of the same brain section (gigantocellular nucleus). The values for glucose utilization, blood flow and capillary density were significantly (P less than 0.05) higher in the VLM than in the reference area (gigantocellular nucleus). This difference was 44.7% for glucose utilization, 34.1% for blood flow and 19.7% for capillary density. These data support the hypothesis that neurons in the VLM are specifically well supplied for being directly regulated in their activity by the PCO2 and pH in the arterial blood.

Animals↗

PubMed1990

Effect of gamma-hydroxybutyrate on local and global glucose metabolism in the anesthetized cat brain.

This study addresses three topics in the chloralose-anesthetized cat: (a) distribution of local CMRglc: values ranging from 5 to 109 mumols/100 g/min were found in 37 brain structures and the mean CMRglc over all examined structures was 30.6 mumols/100 g/min; (b) effect of gamma-hydroxybutyrate (GHB, 250 mg/kg i.v.) on local CMRglc, which was significantly (p less than 0.05) depressed in 16 of 37 structures, most prominently in the auditory system, and the mean CMRglc over all structures after GHB was 20.4 mumols/100 g/min; and (c) global values of CMRglc, CMRO2, and CBF before and after GHB: in these experiments, a modified Kety-Schmidt technique was employed measuring saturation/desaturation of inhaled H2 and concentrations of glucose and oxygen in aortic and sagittal sinus blood. CBF and CMRO2 were not altered after GHB, whereas CMRglc was significantly decreased from 35.7 to 28.8 mumols/100 g/min. The values of CMRglc obtained with both techniques (autoradiography and the Kety-Schmidt technique) are concordant, especially when considering the different sampling areas of both methods. The main finding of the present study is a reduction in cerebral glucose consumption after GHB, irrespective of the technique of measurement. This reduction occurs at an unchanged CMRO2 and CBF.

Animals↗

PubMed1990

Congruence of total and perfused capillary network in rat brains.

In awake normocapnic rats, the density of the total and of the perfused capillary network was determined in 10 brain areas. The density of perfused capillaries was measured by using fluorescein isothiocyanate (FITC) globulin or Evans blue as intravenous marker and by fluorescent microscopy. The density of morphologically existing capillaries was determined according to either the histochemical alkaline phosphatase method or a newly developed immunohistochemical fluorescent method that allows marking of the capillary wall constituent fibronectin with a primary antibody directed against fibronectin. This antibody is made visible by a second FITC-coupled antibody (indirect immunofluorescence). Comparison of perfused and existing capillary counts revealed high congruence when fluorescent results were compared. In contrast, the alkaline phosphatase technique yielded capillary counts that were consistently 30% lower than the fibronectin and the FITC globulin counts. The identity of the perfused and the morphologically existing capillary network could be confirmed by a newly developed double-staining technique. First, the perfused capillaries were quantified by intravascular Evans blue. Then, the existing capillaries were relocated in the same measuring field by the fibronectin technique. Such double staining resulted in identical capillary counts in 97% of all cases. The following conclusions have been reached: 1) Fluorescent methods show a perfusion of virtually all capillaries in the brain of the awake normocapnic rat. 2) The alkaline phosphatase technique appears to underestimate the capillary density in the rat brain.

Acid-Base Equilibrium↗

PubMed1989

Lack of capillary recruitment in the brains of awake rats during hypercapnia.

The present study investigates the question of whether increases in CBF induced by hypercapnia in awake rats are accompanied by increases in the number of perfused capillaries. For the detection of perfused capillaries, gamma-globulin-coupled fluorescein isothiocyanate was injected intravenously. In 10 brain structures the density of perfused capillaries per square millimeter was determined from coronal sections using a highly sensitive fluorescent microscopical method that, in contrast to others, avoided air drying of the frozen brain sections. The results showed an inhomogeneous local distribution of the density of perfused capillaries during normo- and hypercapnia. The density of perfused capillaries was unchanged during hypercapnia compared with normocapnia, although blood flow was markedly increased. It is concluded that a capillary recruitment does not exist in the brain during the high-flow situation of hypercapnia.

Animals↗

PubMed1989

Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis.

Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-[14C]antipyrine and 2-[14C]deoxy-D-glucose method. The treatment induced moderate [15 days, base excess (BE) 16 mM] to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis.

Alkalosis↗