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Biomedical subjects

W Kuschinsky

Publications and source records attributed to W Kuschinsky.

At least 91 records · Page 5Linked to original sources
PubMed1989

Consequences of chronic K+ depletion for the ionic composition of brain, heart, skeletal muscle and cerebrospinal fluid.

Chronic dietary K+ depletion was induced in rats for up to 90 days. The treatment induced hypokalemia, moderate hypernatremia, and moderate metabolic alkalosis which was partly compensated for by a hyperproteinemic acidosis at an unchanged arterial PCO2. Whereas the K+ content of skeletal muscle was reduced to almost half its regular content, the heart muscle was much less affected and the brain K+ content was minimally reduced or not affected depending on the duration of the K+ depletion. The reduction in muscle tissue K+ content was not fully compensated for by an increase in Na+ content. Cerebrospinal fluid K+ and H+ concentrations were decreased during K+ depletion. This may explain the decreased cerebral blood flow measured during K+ depletion at an unchanged cerebral metabolic rate for glucose.

Animals↗
PubMed1988

Local cerebral glucose utilization of the awake rat during chronic administration of nicotine.

Local cerebral glucose utilization (LCGU) was measured in 45 regions of the rat brain during chronic nicotine infusion using the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose method described by Sokoloff et al. [J. Neurochem., 28 (1977) 897-916]. Osmotic minipumps, filled with L-nicotine, were implanted 14 days before the measurement of LCGU. The infused nicotine dose of 12.5 micrograms/kg/min resulted in a plasma nicotine concentration of 77 +/- 17 and a plasma cotinine concentration of 504 +/- 137 (mean +/- S.E.M.) ng/ml plasma. One day before the LCGU experiment was performed, spontaneous locomotor activity was measured and found to be reduced significantly. Measurement of LCGU showed a significant increase in 6 of the 45 brain structures examined, i.e. globus pallidus, septal nucleus, lateral geniculate body, superior colliculus (superficial grey layer), interpeduncular nucleus and optic chiasm. These results are partly congruent with previous data of our group obtained during acute nicotine infusion, insofar as LCGU was increased in the optic chiasm, the lateral geniculate body, the superior colliculus, and the interpeduncular nucleus. On the other hand, the increased LCGU in the globus pallidus and septal nucleus occurred during chronic infusion only; other structures were not affected by chronic infusion although their LCGU had been raised during acute infusion. It is concluded that chronic nicotine infusion has distinct effects on the functional activity of several brain structures which are partly congruent with those affected during acute nicotine infusion and partly divergent from them.

Animals↗
PubMed1988

Cerebral blood flow, glucose use, and CSF ionic regulation in potassium-depleted rats.

Rats were kept on a low-K+ diet for 25 or 70 days. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 31 different structures of the brain by means of the [14C]iodoantipyrine and [14C]2-deoxy-D-glucose method. After 25 and 70 days of K+ depletion LCBF was decreased significantly in 27 and 30 structures, respectively, the average decrease being 19 and 25%. In contrast, average LCGU was not changed. Cisternal cerebrospinal fluid (CSF) K+ concentration decreased significantly from 2.65 +/- 0.02 mM in controls to 2.55 +/- 0.02 mM and 2.47 +/- 0.02 mM in the two treated groups (P less than 0.01). CSF [HCO3-], pH, and PCO2 were increased in K+-depleted animals. These data show that K+ depletion induces an increase in CSF pH and a decrease in CSF K+ concentration, both of which cause a reduction in cerebral blood flow. The increased CSF PCO2 is secondary to the reduction of blood flow, since brain metabolism and arterial PCO2 remained constant.

Acid-Base Equilibrium↗
PubMed1988

The effect of an acute nicotine infusion on the local cerebral glucose utilization of the awake rat.

The effect of acute infusion of nicotine on local cerebral glucose utilization (LCGU) was studied in discrete regions of the central nervous system of the rat by means of the quantitative autoradiographic (14C)2-deoxy-D-glucose method described by Sokoloff et al. Nicotine was administered in three dosages: 0.5 microgram/kg/min, 1.58 micrograms/kg/min, and 5 micrograms/kg/min. The resulting plasma concentrations of nicotine were 10/39/114 ng/ml plasma. During the experiment blood pressure, heart rate, body temperature, hematocrit, acid-base status, and plasma glucose concentration showed no or minor changes. Nicotine significantly increased LCGU in a dose-dependent manner in the following 9 of 45 examined structures: substantia nigra (compact part), superior colliculus (superficial grey layer), interpeduncular nucleus and cingulate cortex (P less than 0.01); lateral geniculate body, optic chiasm, anteroventral and anteromedial nucleus of thalamus and mamillary body (P less than 0.05). For most of these structures with increased LCGU, other investigators have reported a high regional receptor binding of nicotine (exception: mamillary body and optic chiasm). It is concluded that nicotine has distinct effects on the functional activity of localized brain areas.

Animals↗
PubMed1987

The effect of an acute nicotine infusion on the local cerebral glucose utilization of the awake rat.

The effect of acute infusion of nicotine on local cerebral glucose utilization (LCGU) was studied in discrete regions of the central nervous system of the rat by means of the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose method described by Sokoloff et al. Nicotine was administered in 3 dosages: 0.5 microgram/kg/min, 1.58 micrograms/kg/min and 5 micrograms/kg/min. The resulting plasma concentrations of nicotine were 10/39/114 ng/ml plasma. During the experiment, blood pressure, heart rate, body temperature, hematocrit, acid-base status and plasma glucose concentration showed no--or minor--changes. Nicotine significantly increased LCGU in a dose-dependent manner in the following 9 of 45 examined structures: substantia nigra (compact part), superior colliculus (superficial grey layer), interpeduncular nucleus and cingulate cortex (P less than 0.01); lateral geniculate body, optic chiasm, anteroventral and anteromedial nucleus of thalamus and mamillary body (P less than 0.05). For most of these structures with increased LCGU, other groups have reported a high regional receptor binding of nicotine (exception: mamillary body and optic chiasm). It is concluded that nicotine has distinct effects on the functional activity of localized brain areas.

Animals↗
PubMed1987

Effect of the muscarinic agonist carbachol on pial arteries in vivo after endothelial damage by air embolism.

Reactions of pial arteries to the muscarinic agonist carbachol were tested in vivo in chloralose anesthetized cats before and after endothelial damage. Moderate endothelial damage was induced by arterial air embolism and verified by electron microscopy for the vessels tested. The experiments had three phases; First, the normal reactivity of pial arteries to carbachol (10(-7) to 10(-5) M) was tested using the microapplication technique, then, after air embolism, the reactivity was reinvestigated at the same vessel. Finally, pial arteries were taken out for scanning electron microscopy. The results show carbachol (10(-6) and 10(-5) M) induced significant dilations under control conditions, also after repetition at the same vessel. After air embolism, the reactions to carbachol were abolished. Morphologic data revealed that whereas control pial arteries showed intact endothelium, the embolized vessels revealed various degrees of endothelial alterations. All showed flattening of endothelial nuclei, to a greater or lesser degree, and in many cases, the endothelium had a wrinkled appearance; several arteries showed severe degradation of the intercellular junctions. It is concluded that (a) carbachol-induced muscarinic vasodilatation of pial arteries in vivo can be abolished after a morphologically verified endothelial lesion--thus confirming in vitro studies in larger arteries and (b) disturbed vascular function does not require rubbing of the endothelium, but occurs already with moderate endothelial damage.

Animals↗
PubMed1987

Moderate hypoxia: reactivity of pial arteries and local effect of theophylline.

The reactivity of pial arteries to the perivascular microapplication of artificial cerebrospinal fluids with mounting concentrations of adenosine (10(-11)-10(-3) M), K+ (0-10 mM), and H+ (pH 5.1-7.6) was determined in chloralose-anesthetized ventilated cats during normoxic control conditions and during moderate normocapnic arterial hypoxia (arterial Po2 47 Torr). Hypoxia induced a significant mean pial arterial dilatation of 18-29% in the various types of experiments. The pial arterial reactivity to each of the tested factors remained unchanged during hypoxia compared with normoxia. The hypoxic vasodilatation could not be reduced by the perivascular microapplication of theophylline (10(-5) and 5 X 10(-5) M). Systemic theophylline (50-75 mumol/kg, iv), regardless of whether given during or before hypoxia, did not attenuate the hypoxic vasodilatation, although it blocked dilatations induced by the perivascular microapplication of adenosine during normoxia. The present study shows that 1) local metabolic factors are vasoactive during moderate hypoxia; therefore they could mediate the hypoxic dilatation of brain vessels; 2) systemic theophylline can block vascular adenosine receptors; 3) since local theophylline had no effect on the hypoxic dilatation of pial arteries, adenosine may not be the main causative factor for the hypoxic hyperemia.

Adenosine↗
PubMed1986

pH-microclimate at the luminal surface of the intestinal mucosa of guinea pig and rat.

Segments of guinea pig jejunum, proximal and distal colon and of rat jejunum were superfused either in vivo or in vitro with different electrolyte solutions. The pH in the bulk phase solution and at the surface of the epithelium was measured with two different types of glass pH-microelectrodes, a pointed tip (Hinke-type) and a flat membrane electrode (Dubuisson-type); both types of electrodes gave the same results. The existence of a pH-microclimate at the surface of the mucosa was demonstrated under both in vivo and in vitro conditions. In vivo the pH-microclimate was stable and virtually independent of changes in the luminal bulk phase pH. When the bulk phase pH of the guinea pig colon was changed between pH 5 and pH 8.6, the mean pH in the microclimate was 7.08 +/- 0.15 (n = 163) in the proximal colon and 6.91 +/- 0.14 (n = 75) in the distal colon. In the guinea pig jejunum pH in the microclimate was 7.37 +/- 0.21 (n = 10) while the luminal pH was 7.27 +/- 0.10. Under in vitro conditions, the pH in the microclimate was more acidic (guinea pig jejunum delta pH 0.93, rat jejunum delta pH 0.40, guinea pig proximal colon delta pH 0.22). Addition of glucose (10 mM) or short-chain fatty acids (80-90 mM) to the luminal solution or replacement of sodium by lithium did not influence the pH in the microclimate significantly. Also the addition of acetazolamide, amiloride, SITS or sodium deoxycholate to the luminal solution, did not affect the pH in the microclimate in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of gamma-hydroxybutyrate on the reactivity of pial arteries before and after ischemia.

The effect of gamma-hydroxybutyrate (GHB) on the reactivity of pial arteries to local metabolic factors was tested in chloralose-anesthetized cats before or after a period of transient ischemia induced by air embolism. The vascular reactions were determined during the perivascular microapplication of artificial CSFs with increasing concentrations of adenosine (10(-11)-10(-3) M), H+ (pH 5.1-7.6), or K+ (0-10 mM). During nonischemic conditions the pial arterial reactivity to adenosine and H+, but not to K+, was significantly increased by GHB (250 mg/kg i.v.) when compared with the control reactivity. After cerebral ischemia the reactivity to adenosine was abolished with and without the administration of GHB prior to air embolism. The reactivity to K+ was partly preserved but not increased by GHB when compared with previous results without GHB. In contrast GHB improved the postischemic reactivity to perivascular H+ that had been found to be abolished in previous experiments without GHB. The perivascular microapplication of GHB showed no influence of GHB on the vascular diameter. An important finding of the present study is the demonstration of an increase in cerebrovascular reactivity, which may give scope for therapeutic improvement of the regulation of CBF in pathophysiological conditions.

Adenosine↗
PubMed1986

Interdependency of local capillary density, blood flow, and metabolism in rat brains.

Previous investigations have established a strong correlation between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). In the present study the relationship between density of perfused brain capillaries and LCBF or LCGU was investigated in conscious and anesthetized rats. Perfused capillaries were stained by labeling the plasma with the gamma globulin-coupled fluorochromes, fluorescein isothiocyanate (FITC) and lissamine-rhodamine B 200 (RB 200). The density of perfused capillaries was determined in 12 different brain structures by fluorescence microscopy of embedded brain sections following coronal sectioning in a cryostat. Significant differences were found among brain structures investigated; the lowest density of perfused capillaries was found in the white matter (e.g., corpus callosum 162 fragments/mm2), whereas the highest values were determined in the structures of the auditory system (e.g., inferior colliculus 810 fragments/mm2). LCBF and LCGU were measured in two separate groups of rats using standard autoradiographic methods. In all three experimental groups, the same structures were identified and measured with a high degree of accuracy and local resolution. Density of perfused capillaries correlated well with LCBF (r = 0.93) and even better with LCGU (r = 0.97). In addition to the relationship between LCGU and LCBF established by earlier studies, these data show the intimate interrelationship between LCGU, density of perfused capillaries, and LCBF.

Animals↗
PubMed1985

Influence of gamma-hydroxybutyrate on the relationship between local cerebral glucose utilization and local cerebral blood flow in the rat brain.

The relationship between local cerebral glucose utilization (LCGU) and local CBF (LCBF) was examined during the action of gamma-hydroxybutyrate (GHB) (900 mg/kg i.v.) in conscious rats. GHB induced discrepant effects on blood flow and metabolism. LCGU was markedly depressed in all structures examined, whereas LCBF was differently affected in that no related changes were observed. Global glucose utilization was markedly depressed (-51%), whereas global blood flow was not significantly altered. The marked dissociation between the changes in global glucose utilization and global blood flow induced by GHB is reflected only to a minor degree in the local values inasmuch as the correlation between LCGU and LCBF was only slightly weakened and its heterogeneity was increased.

Animals↗
PubMed1983

The effects of intravenous norepinephrine on the local coupling between glucose utilization and blood flow in the rat brain.

Norepinephrine was infused intravenously in two groups of normal, awake rats. In one group local cerebral glucose utilization (LCGU) was measured by the deoxyglucose method (Sokoloff et al. 1977b); in the other group local cerebral blood flow (LCBF) was determined by the iodoantipyrine method (Sakurada et al. 1978). The experiments were performed during a stable state in which the heart rate was reduced between 36% (LCGU experiments) and 27% (LCBF experiments). Norepinephrine infusion reduced LCGU in all 39 structures measured between - 18 and - 37% from control values obtained in a group of normal non-infused rats. The decrease in LCGU was significant (P less than 0.05) in 38 of the 39 structures tested. LCBF was increased but not statistically significantly in most of the structures examined. When the LCGU values of the various structures during norepinephrine infusion were correlated with their corresponding LCBF values, a tight correlation (r = 0.94) was found indicating a close coupling between LCGU and LCBF during norepinephrine infusion. When compared to the relationship between LCGU and LCBF in a normal, non-infused control group, the slope of the regression line was increased significantly (P less than 0.01) by the norepinephrine infusion, indicating a resetting of the coupling mechanism. This means that, at a given metabolic rate, a higher blood flow is needed to perfuse a brain structure during norepinephrine infusion than during control conditions.

Animals↗
PubMed1981

Local cerebral glucose utilization and blood flow during metabolic acidosis.

The relationship between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) was studied in two groups of normal conscious rats. LCGU was measured by the [14C]deoxyglucose technique and LCBF by the [14C]iodoantipyrine technique. When the LCGU of 39 brain structures was correlated with their respective values of LCBF an excellent correlation (r = 0.96) was obtained between LCGU and LCBF, demonstrating a tight coupling at a local level. Chronic metabolic acidosis was induced in two other groups of rats by adding 0.35 M NH4Cl to the drinking water for 5-6 days. This resulted in a significant (P less than 0.01) reduction in overall cerebral glucose utilization (-29%) and a nonsignificant reduction in overall cerebral blood flow (-8%). This dissociation between the overall cerebral glucose utilization and blood flow during metabolic acidosis cannot be taken as an indicator of uncoupling because the values for LCGU were still well correlated (r = 0.95) with the values for LCBF, indicating a resetting of the coupling mechanism to a new level.

Acidosis↗
PubMed1979

Unimportance of perivascular H+ AND K+ activities for the adjustment of pial arterial diameter during changes of arterial blood pressure in cats.

The role of perivascular H+ and K+ in the adjustment of pial arterial diameter during changes in arterial blood pressure was investigated in chloralose anesthetized cats. Blood pressure was reduced by i.v. mecamylamine or pentolinium and was increased by i.v. hypertensin. Pial arterioles and arteries with a control diameter ranging from 37--218 microns at a spontaneous mean arterial blood pressure of 128 +/- 16 (SD) mm Hg were studied. Vascular diameter as measured by TV image splitting showed the typical reactions, i.e. constriction during increase (up to 200 mm Hg) and dilation during decrease in blood pressure (down to 60 mm Hg). Perivascular H+ and K+ activities were measured using pH microelectrodes (Hinke type) and K+ ion exchanger microelectrodes, respectively. Under control conditions perivascular pH was 7.25 +/- 0.11 (SD) and K+ activity was 2.46 +/- 0.65 (SD) mM, respectively. During changes in blood pressure the vascular reactions of pial arteries were not accompanied by significant alterations in perivascular H+ or K+ activity. From these data it can be concluded that mechanisms other than those which are mediated by H+ or K+ are involved in the adjustment of pial arterial diameter during changes in arterial blood pressure.

Angiotensin II↗