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Biomedical subjects

E Dóra

Publications and source records attributed to E Dóra.

At least 37 records · Page 2Linked to original sources
PubMed1984

A simple cranial window technique for optical monitoring of cerebrocortical microcirculation and NAD/NADH redox state. Effect of mitochondrial electron transport inhibitors and anoxic anoxia.

Fluorescence of NADH and vascular volume of the brain cortex of chloralose-anesthetized cats were measured by surface fluororeflectometry. A cranial window and superfusion technique was elaborated for the topical inhibition of mitochondrial electron transport in the brain cortex by amytal (inhibits at site I) and cyanide (inhibits at site III). The changes in NAD/NADH redox state and CVV evoked by these electron transport inhibitors were compared with those elicited by anoxic anoxia. Amytal (10(-3)-10(-1) M) and cyanide (10(-5)-10(-2) M) resulted in a concentration-dependent and reversible increase in cortical NAD reduction and vascular volume, but the cerebrocortical vessels were almost completely dilatated long before maximum NAD reduction was reached. Cyanide at 10(-2) M increased cortical NAD reduction and vascular volume as much as anoxic anoxia. Amytal at 10(-1) M induced approximately half of the NAD reduction evoked by 10(-2) M cyanide or anoxic anoxia, but resulted in only slightly less vasodilatation than that following cyanide and anoxic anoxia. Since amytal inhibits mitochondrial electron transport at site I--and cyanide and anoxia at site III--but induces a comparable degree of vasodilatation, it is concluded that cytochrome oxidase cannot be the single molecular oxygen sensor in the brain cortex.

Amobarbital↗
PubMed1984

Effect of the adrenergic beta receptor blocker propranolol on the dilatation of cerebrocortical vessels evoked by arterial hypoxia.

In order to elucidate the importance of adrenergic beta receptors in the regulation of cerebral microcirculation during arterial hypoxia, chloralose anaesthetized cats were treated with propranolol hydrochloride. Arterial hypoxia, lasting for approximately 4 min, was induced by respiring the animals with a gas mixture containing 7% oxygen balanced in nitrogen gas. Arterial hypoxia was induced in the same animals before and during continuous infusion of propranolol (0.05 mg/kg/min into the lingual artery). Cerebrocortical vascular volume ( CVV ) and NADH fluorescence were measured through a cranial window with a microscope fluororeflectometer . Control arterial hypoxia (no treatment) increased CVV and NADH reduction by 22.2 +/- 2% and 20.4 +/- 2.1%, respectively. Following 1 mg/kg propranolol treatment arterial hypoxia of the same severity resulted in only approximately 2/3 of the CVV response obtained during the control arterial hypoxia. Since arterial hypoxia induced similar changes in arterial blood gases, arterial blood pressure, and intracranial pressure in both cases, our results indicate that the cortical vasodilatation occurring during arterial hypoxia is due, at least in part, to the activation of adrenergic beta receptors.

Animals↗
PubMed1983

Effect of topically administered epinephrine, norepinephrine, and acetylcholine on cerebrocortical circulation and the NAD/NADH redox state.

We investigated the effects of topically administered catecholamines and acetylcholine (ACh) on the cerebrocortical microcirculation and NAD/NADH redox state in chloralose-anesthetized cats. NADH fluorescence of the brain cortex and the volume of small intracortical vessels were measured by fluororeflectometry, and in most of the experiments the pial vessels were photographed simultaneously through a cranial window. Cerebrocortical vascular volume (CVV) and the diameter of the pial vessels were decreased, and NADH was oxidized by concentrations of epinephrine and norepinephrine as low as 3 x 10(-8) M. Pial veins constricted approximately twice as much as pial arteries. ACh dilatated pial arteries, slightly constricted pial veins, and increased CVV, but had no effect on the NAD/NADH redox state. Since pial and intracortical vessels were constricted markedly by catecholamines, and since these vascular reactions appeared at a lower concentration than is presumed to occur in the synaptic cleft, our results support the regulating role of these substances in cerebral circulation. NADH oxidation, obtained with catecholamines, was interpreted to be due to enhanced tissue respiration. The finding that ACh dilatated pial arteries and increased CVV, but failed to influence the NAD/NADH redox state, might indicate that the brain cortices of normal animals are bioenergetically nonhypoxic. If cortical microregions where the oxygen tension is close to zero were biochemically hypoxic, NADH oxidation should have occurred during ACh administration.

Acetylcholine↗
PubMed1983

Glycolysis and epilepsy-induced changes in cerebrocortical NAD/NADH redox state.

The effects of topical inhibition of glycolysis on epilepsy-induced changes of cortical vascular volume (CVV) and fluorescence of reduced nicotinamide adenine dinucleotide (NADH) were investigated in chloralose-anaesthetized cats. CVV and NADH fluorescence were measured by a microscope fluororeflectometer. It was found that 30 min of superfusion of the brain cortex with artificial cerebrospinal fluid (CSF) containing 0.5 mM sodium iodoacetate (IAA) resulted in a 16.4 +/- 0.8% increase in CVV, and 6.6 +/- 0.5% in NADH oxidation. IAA did not alter the electrical activity of the brain cortex. Epileptic seizures in the nonsuperfused brain cortex and following 30 min superfusion of the brain cortex with mock CSF resulted in changes (not significantly different) in CVV and NAD/NADH redox state. They increased CVV and NAD reduction by 28-32% and 7-10%, respectively. Following 0.5 mM IAA treatment of the brain cortex, epileptic seizures led to greatly reduced vascular responses and induced NADH oxidation instead of NAD reduction. Since the topical inhibition of glycolysis reversed the direction of NAD/NADH redox responses accompanying epilepsy, it may be suggested that the relative rate of substrate mobilization as compared with the rate of mitochondrial electron transport is the factor that determines the actual change in NAD-NADH ratio during excessive brain activations. However, contrary to the situation in vitro (isolated mitochondria), the NAD/NADH redox state of the intact brain cortex is not shifted toward oxidation but to reduction during increased electrical activity.

Animals↗
PubMed1982

Effect of acute arterial hypo- and hypertension on cerebrocortical NAD/NADH redox state and vascular volume.

The effects of stepwise arterial hypotension (MABP: 80, 60, 40 mm Hg) and moderate arterial hypo- and hypertension (MABP: 80, 150-160 mm Hg) on cerebrocortical vascular volume and NAD/NADH redox state were studied in anaesthetized cats. The vascular volume and NADH fluorescence measurements were performed on closed skull preparations using a microscope fluororeflectometer. To determine the possible role of adrenergic alpha-receptors in the autoregulatory adjustment of cerebrocortical vascular volume, some of the animals were pretreated with intra-arterially infused phenoxybenzamine (1 mg/kg). It was found that longlasting stepwise arterial hypotension leads to a gradual increase in cerebrocortical vascular volume and NADH fluorescence. Though the cerebrocortical arteries dilatated considerably at 80 mm Hg, sustained for 30 min, the NAD/NADH redox state failed to be reoxidized but was shifted to a more reduced state. This finding suggests that some factor other than tissue hypoxia is responsible for the dilatation of cerebrocortical vessels during moderate arterial hypotension. When the arterial blood pressure was restored following stepwise arterial hypotension, the cerebrocortical vascular volume did not decrease and the NAD/NADH redox state remained reduced, showing that the autoregulatory capability of the vessels was lost and the tissue metabolism was irreversibly altered. During a 5-min duration of moderate arterial hypo- and hypertension, biphasic changes were obtained in cerebrocortical vascular volume while the NAD/NADH redox state was shifted to a more reduced and oxidized state. Since the dilatation and the constriction of the cerebrocortical vessels during arterial hypo- and hypertension lagged by 40-80 s behind the redox state alterations, it is suggested that the myogenic mechanism has a minor role in CBF autoregulation. Phenoxybenzamine (PBZ) dilatated the cerebrocortical vessels, indicating the existence of an active alpha-receptor-mediated vasoconstrictory tone. Since the extent of autoregulatory vascular volume changes was not affected by PBZ pretreatment, the involvement of adrenergic alpha-receptors in the autoregulation of CBF can be excluded, at least for cats.

Acute Disease↗
PubMed1980

Shock-induced cytoplasmic NADH fluorescence changes in the living cat brain cortex: effect of dexamethasone.

The effect of dexamethasone administration on cerebrocortical NADH fluorescence, blood flow and blood volume, intracellular oxygen tension and electrocorticogram (ECoG) was studied in anaesthetized cats in two sets of experiments. Haemorrhagic shock was induced by stepwise decrease of mean arterial blood pressure from the control level a to 80, 60 and 40 mmHg. The bleeding was followed by reinfusion of the shed blood. The method of producing shock was identical in the untreated and dexamethasone treated groups. Dexamethasone was administered in the control period. The results are summarized as follows: (a) Dexamethasone, given in pharmacological doses failed to alter blood flow or blood volume, NADH fluorescence and the intracellular oxygen tension in the cerebral cortex of the cat; (b) Haemorrhagic shock resulted in a marked increase of cytoplasmic NADH fluorescence in the untreated group, while these changes were much smaller in the dexamethasone pretreated animals; (c) Dexamethasone pretreatment significantly reduced the extent of shock-induced cortical vasodilatation. In some experiments the brain cortex became ischaemic at 40 mmHg MABP; (d) Dexamethasone pretreatment failed to eliminate the shock-induced decrease in cortical intracellular oxygen tension and the irreversible deterioration of ECoG. It is suggested that the decrease in cortical cytoplasmic NAD reduction and the concomitant lactate acidosis might be involved in the ability of dexamethasone to control oedema during shock and other pathological conditions.

Animals↗
PubMed1979

Mechanism of the cerebrocortical vasodilatation during anoxia.

The possible role of cerebrocortical ion homeostasis, NAD/NADH redox state and of cortical oxygen tension was investigated in the initiation of hypoxic cortical vasodilatation. In addition, changes in cerebrocortical extracellular concentrations of Na+, K+, and Cl- during anoxia were studied. The results were as follows. a) The cerebrocortical reflectance decrease, e.g. cerebral vasodilatation, lagged behind the cortical pO2 decrease by 1-2 sec, but preceded the decrease of arterial blood pressure and ECoG as well as the extracellular Na+, K+, Cl- increases by 20-30 sec. Since the cortical pO2 decreased first and the ion changes lagged behind the onset of vasodilatation by 20-30 sec, it is suggested that the CBF increase in hypoxia is mediated via the cortical pO2 decrease. b) A significant NAD reduction was already present after 20 sec. of nitrogen breathing. Since the ECoG and MABP decreased, and K+ activity increased much later than this, it is presumed that the NAD reduction during the first 30-40 sec of anoxia indicates an increased rate of glycolysis, but not mitochondrial hypoxia. c) In the predepolarization phase a 17% K+, 4% Na+, 5% Cl- increase is probably the result of a reduction of the extracellular spaces caused by water movement and by the migration of Na+ and Cl- from the extracellular to the intracellular space. The large K+, Na+, Cl- changes during terminal depolarization can be interpreted as a result of the failure of the membrane bound Na+ -K+ pump and of the altered ion permeability of the cell membranes.

Action Potentials↗
PubMed1979

Effect of arterial hypoxia on the cerebrocortical redox state, vascular volume, oxygen tension, electrical activity and potassium ion concentration.

The effect of different degrees of arterial hypoxia on cerebrocortical NAD/NADH redox state, reflectance, oxygen tension, extracellular potassium ion concentration, ECoG and arterial blood pressure was investigated in rats. The results may be summarized as follows. a) The decrease of cortical pO2 preceded the dilatation of cortical vessels by 15-20 sec but the changes in cortical extracellular potassium ion concentration, ECoG and arterial blood pressure started later than the vasodilatation. These results give further support to the regulatory role of cortical pO2 decrease in the initiation of cerebrocortical vasodilatation during arterial hypoxia. b) Since the K+ concentration of the brain cortex and the ECoG did not change in mild arterial hypoxia, the significant NAD reduction obtained in this experimental group is likely to be of cytoplasmic origin. The same conclusion applies to the initial periods of severe arterial hypoxia. On the basis of the extent of NAD reduction during various degrees of arterial hypoxia it is concluded that about 30% of the NAD reduction occurring in anoxia is of cytoplasmic origin. c) When the animals were ventilated with a gas mixture containing 4-7% oxygen, the brain cortex became nearly anoxic, partly because of the gradual decrease of arterial blood pressure. Finally, the mechanism of potassium leakage is identical under prolonged severe arterial hypoxaemia and on anoxic terminal depolarization.

Action Potentials↗
PubMed1979

Intracellular oxygen tension and energy metabolism in the cat brain cortex during haemorrhagic shock.

The changes in intracellular oxygen tension and energy metabolism of the cat brain cortex were studied by surface fluororeflectometry during haemorrhagic shock. The results may be summarized as follows. (a) Intracellular oxygen tension, i.e. the maximum cortical NAD reduction obtained during nitrogen gas inhalation decreased gradually during the hypovolaemic phase of shock and finally, the brain cortex became ischaemic. (b) Partial uncoupling of the cerebrocortical mitochondrial respiration and oxidative phosphorylation appeared in the very early period of bleeding, as indicated by the overshot of the cortical NAD/NADH redox state towards oxidation subsequent to the cessation of nitrogen gas inhalation. Partial uncoupling of mitochondrial respiration and oxidative phosphorylation became more pronounced during the later phases of bleeding, finally, the mitochondrial electron transport stopped. In line with these changes the frequency and the amplitude of ECoG decreased gradually and markedly during the hypovolaemic phase of shock. (c) Microcirculation and energy metabolism of the cat brain cortex were severely and irreversibly damaged during the hypovolaemic phase of shock. This was clearly shown by the fact that in the majority of experiments the nitrogen anoxia after reinfusion failed to bring about changes in the cortical NAD/NADH redox state and the ECoG changes occurred during bleeding did not improve after reinfusion. It is concluded that the early disturbances of cerebrocortical energy metabolism play an important role in the development of neural and vascular lesions of the brain that occur during haemorrhagic shock.

Action Potentials↗
PubMed1979

Reactivity of the cerebrocortical vasculature and energy metabolism to direct cortical stimulation in haemorrhagic shock.

Direct electrical stimulation of the cerebral cortex was used to determine the changes of cortical carbohydrate and oxidative metabolism and of vascular reactivity during haemorrhagic shock. The results were as follows. 1. Electrical stimulation of the brain cortex applied in the control period led to a marked vasodilation and NAD reduction that was preceded in part of the experiments by a transient NADH oxidation. It is suggested that the increase in cortical NADH fluorescence observed during direct stimulation is due to the fact that the rate of cytoplasmic NADH production exceeded the rate of mitochondrial NADH oxidation and of the rate of H+-transport from the cytoplasm into the mitochondria. 2. The cerebrocortical vascular and NAD/NADH redox state responses induced by electrical stimulation changed in the early hypovolaemic phase of shock. At this time, electrical stimulation of the brain cortex led to NADH oxidation in the majority of the experiments or in some experiments, the stimulation did not bring about changes in the redox state of the cortex. The total loss of the reactivity to direct stimulation of the cerebrocortical vessels and of energy metabolism preceded the occurrence of cortical ischaemia during the hypovolaemic phase of shock. 3. Since after reinfusion of the shed blood, redox state and vasculature remained unresponsive to stimulation even in those experiments in which the cortical ischaemia improved, it is concluded that the carbohydrate and oxidative metabolism of the brain cortex were already irreversibly damaged in the early phase of hypovolaemic shock.

Action Potentials↗
PubMed1976

Metabolic and electron microscopic studies post mortem in brain mitochondria.

The RCR of malate+glutamate oxidation of isolated rat brain mitochondria decreased with increasing duration of anoxia and it ceased completely in the 12 hour ischemic group. After one hour of ischemic anoxia neither the respiration of mitochondria nor their morphology altered irreversibly. There is a strong correlation between the ultrastructural changes and RCR value of mitochondria, namely the RCR decreased proportionally with increasing number of light type of mitochondria. From our results we can conclude that the dense form seems to be the functional form, while the light mitochondrial structure is a transition to the non functioning homogenous type of brain mitochondria.

Adenosine Diphosphate↗