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T J Sick

Publications and source records attributed to T J Sick.

At least 73 records · Page 4Linked to original sources
PubMed1987

Seizure-associated pulmonary edema and cerebral oxygenation in the rat.

Cerebral partial pressure of O2 (PO2), relative changes in the ratio of reduced/oxidized cytochrome aa3, blood flow, and the arteriovenous difference in O2 content were measured during seizures with and without pulmonary edema. Seizures were induced with bicuculline (0.2-1.2 mg/kg iv) in rats anesthetized with 70% N2O and paralyzed with curare. Briefer seizures were accompanied by increased cerebral PO2 and increased oxidation of cytochrome aa3. Lung water content and arterial O2 partial pressure (PaO2) remained normal. Longer duration seizures were also accompanied initially by increases in cerebral oxygenation. Within minutes, however, PaO2 fell from a mean of 118 to 51 mmHg, and lung water content increased from 76.2 to 83.6%. Cerebral PO2 fell but most often rose back to or above control levels, while cytochrome aa3 became markedly reduced. Simultaneously, cerebral blood flow increased more than 300% above preseizure values and O2 delivery increased more than O2 consumption. The reductive shift of cytochrome aa3 was greater than that produced by lowering PaO2 to equivalent values in seizure-free rats. The reductive shift of cytochrome aa3, despite increased O2 delivery, may be indicative of derangements in cerebral O2 diffusion or energy metabolism.

Animals↗
PubMed1985

A rapid-scanning spectrophotometer designed for biological tissues in vitro or in vivo.

Rapid and sensitive detection of optical signals from biological materials has been very useful in studies of cell physiology and biochemistry. A rapid-scanning spectrophotometer is described here that has the following advantages: (i) it can be used in transmission or reflection modes, (ii) it can rapidly accumulate spectra and simultaneous kinetic data, (iii) it has high accuracy and sensitivity, and (iv) it can analyze and store large amounts of spectral information. Evaluations described here are aimed toward the measurement of reduction/oxidation shifts of mitochondrial cytochromes in tissues, but the flexibility of the optical components makes this spectrophotometer adaptable to the study of light absorption changes of intrinsic or extrinsic optically active molecules in a variety of light scattering preparations, tissues, and organs in vitro or in vivo.

Animals↗
PubMed1985

A computer-assisted rapid-scanning spectrophotometer with applications to tissues in vitro and in vivo.

A flexible approach is described to acquire, store, retrieve, and manipulate the large volume of data provided by a rapid-scanning spectrophotometer designed for biological preparations. Data can be displayed in spectral and kinetic formats. This spectrophotometer provides a means to simultaneously measure the concentrations of components of light scattering preparations and to record chemical reactions as they occur. Although application of this instrument for the study of reduction/oxidation shifts of mitochondrial respiratory chain components is emphasized, the design is suitable for many spectrophotometric applications.

Animals↗
PubMed1985

Mitochondrial redox responses to cerebral ischaemia produced by four-vessel occlusion in the rat.

Changes in reduction/oxidation (redox) ratios of the initial and terminal members of the mitochondrial respiratory chain (nicotine adenine dinucleotide and cytochrome a,a3) were measured by fluorometry and reflection spectrophotometry in rat cerebral cortex. Three patterns of responses were observed during the transition to global ischaemia produced by electrocoagulation of the vertebral arteries and carotid artery ligation. Most often, arterial occlusion was accompanied by shifts towards reduction of the mitochondrial components followed by partial reoxidation and then further reduction. Less frequently, ischaemia produced reductive shifts of the respiratory chain reactants that rapidly reached maximal values. In some rats, however, arterial, occlusion produced mitochondrial reduction followed by partial or complete reoxidation. ECoG remained suppressed, despite mitochondrial reoxidation, in approximately 1/3 of the latter animals. This study demonstrates that responses to 4-vessel occlusion can vary greatly among animals and suggests that monitoring of signals of ischaemic insult, such as mitochondrial redox status, may offer advantages for assessment of the consequences of ischaemic insult.

Anesthesia, General↗
PubMed1985

Potassium ion homeostasis and mitochondrial redox status of turtle brain during and after ischemia.

To account for the remarkable capacity of turtle brain to survive without oxygen, microelectrode recordings of extracellular potassium activity (K+o) were made in intact brains of normoxic pentobarbital-anesthetized turtles during and after ischemia. Changes in redox status of brain cytochrome a,a3 were recorded simultaneously by reflection spectrophotometry. Cytochrome a,a3 became fully reduced, and K+o rose at a slow rate for approximately 60 min during complete ischemia. When K+o reached 8-12 mM, an inflection point was observed after which K+o rapidly increased to levels above 30 mM. Full recovery of baseline K+o and cytochrome a,a3 redox state occurred only if brain blood flow was restored within 60 min. These data demonstrate that maintenance of ion homeostasis in turtle brain depends on blood flow and continued delivery of systemic substrates and that viability is threatened if ischemia is prolonged beyond 60 min.

Animals↗
PubMed1984

Concepts of brain oxygen sufficiency during seizures.

To resolve conflicting evidence of oxygen sufficiency or insufficiency during seizures, signals of metabolic and circulatory function were monitored in rat cerebral cortex during recurrent seizures. Early seizures were accompanied by increased blood volume, increased tPO2, and oxidative shifts of cytochrome a,a3, indicative of oxygen sufficiency. Later seizures were accompanied by a smaller increment in blood volume, a fall in tPO2, and shifts toward reduction of cytochrome a,a3, suggesting that cerebral oxygen supply became insufficient to meet demand. Responses suggesting oxygen insufficiency occurred during short duration ictal bursts, interictal spikes or electrocortical stimulation at times when longer duration ictal episodes still were accompanied by responses signalling oxygen sufficiency. These data indicate that there is a progressive dissociation of the normally tight couple between neuronal activity, energy demand, and cerebral blood flow during status epilepticus. Systemic derrangements that often accompanied recurrent seizures also contributed to decreased cerebral oxygenation. These factors may cause the neuronal damage reported to follow prolonged status epilepticus.

Animals↗
PubMed1984

Relationships between aerobic and anaerobic energy production in turtle brain in situ.

To define the relationships between brain mitochondrial activity and high-energy intermediates in the turtle, brains were frozen in situ at times determined by the reduction-oxidation status of cytochrome a,a3. Increases in brain lactate indicated that transition to anaerobiosis occurred while oxidative reactions were still ongoing during hypoxia and that the signal for anaerobiosis is not the complete failure of mitochondrial electron transfer. Decreases in creatine phosphate (CrP), ATP, ADP, and AMP demonstrate that their consumption exceeded production during hypoxia. CrP decreased further during the following 120 min of anoxia, but ATP, ADP, and AMP were not significantly altered from control values. These data suggest that ATP is not inhibitory to rate-limiting, key glycolytic enzymes such as phosphofructokinase. Calculations indicate that ATP production declined during anoxia. This study indicates that decreased CrP values, decreased ATP production, and high lactate levels do not preclude ion homeostasis and electrical activity of turtle brain and that this brain is protected against lactate or pH damage during anoxia, in contrast to mammalian brain.

Adenine Nucleotides↗
PubMed1983

Importance of vascular responses in determining cortical oxygenation during recurrent paroxysmal events of varying duration and frequency of repetition.

Cerebral oxygenation initially increases and later decreases in rats subjected to experimental status epilepticus. In this study, we have compared cerebral oxygen supply and vascular changes during paroxysmal events of different durations and at different time intervals to test the hypothesis that oxygen insufficiency is associated more readily with paroxysmal events of greater intensity. Continuous measurements were made of local changes in cortical blood volume, redox levels of cytochrome a, a3, cortical Po2, and systemic arterial blood pressure during recurrent seizures induced by pentylenetetrazol or bicuculline. In contrast to expectations, systemic and cerebral vascular responses and associated increases in cerebral oxygenation were better maintained during long-duration ictal episodes than during short-duration ictal bursts, interictal spikes, or evoked potentials. Short-duration paroxysmal events were often accompanied by decreases in cerebral oxygenation, whereas long-duration events were still accompanied by increases in oxygenation. Ictal bursts occurring with short interburst intervals caused a more rapid failure of vascular responsiveness than those occurring at longer intervals. These relationships of intensity and frequency of repetition of seizures to changes in vascular responses indicate progressive dissociation of the normally tight couple between neuronal activity, energy demand, and cerebral blood flow during status epilepticus.

Animals↗
PubMed1983

Oxidative metabolic responses during recurrent seizures are independent of convulsant, anesthetic, or species.

A transition from sufficient to insufficient cerebral oxygenation has been reported during recurrent seizures, but it was unknown whether this phenomenon was limited to particular species, anesthetics, or convulsant agents. Focal measurements were made of cortical PO2 and redox changes of cytochrome a, a3 in rats and cats anesthetized with sodium pentobarbital, nitrous oxide, or ketamine, or decerebrated. Seizures were induced with pentylenetetrazol, bicuculline, or electroconvulsive shock. Transition from oxygen sufficiency to insufficiency always occurred in association with inadequate vascular responses, regardless of experimental conditions. These results indicate that transition is a general characteristic of experimental status epilepticus.

Anesthetics↗
PubMed1982

Does endogenous norepinephrine regulate potassium homeostasis and metabolism in rat cerebral cortex?

The role of endogenous cerebral norepinephrine (NE) as a modulator of transmembrane cation transport and energy metabolism was evaluated by monitoring extracellular potassium ion activity ([K+[o) in vivo and by measuring cortical Na+,K+-ATPase activity and oxygen consumption in vitro. Ipsilateral cortical NE was depleted by unilateral 6-hydroxydopamine (6-OHDA) lesions of the locus ceruleus (LC). The contralateral cortex was used for control measurements. NE depletion had no effect on resting levels of cortical [K+[o or on the rate of K+ removal from the extracellular space following direct cortical stimulation. There was also no effect of NE depletion on Na+,K+-ATPase activity in cortical homogenates nor on oxygen consumption of cortical slices over a wide range of K+ concentrations. These results indicate tht central NE depletion does not influence movements of cortical K+ either directly through an influence on Na+,K+-ATPase activity or indirectly through effects on oxidative metabolism. It is probable, therefore, that previously described effects of NE on cortical oxidative metabolism are mediated through changes in cerebral perfusion and/or modification of substrate availability in vivo.

Animals↗
PubMed1982

Brain potassium ion homeostasis, anoxia, and metabolic inhibition in turtles and rats.

Microelectrode measurements of tissue oxygen tension (PtO2) and extracellular potassium ion concentration ([K+]o) and dual wavelength spectrophotometric measurements of the reduction/oxidation state of cytochrome aa3 were used to compare the resistance of turtle and rat brain to anoxia in vivo. In both species, respiration with 100% N2 resulted in a decrease of tissue oxygen tension to near 0 mmHg and reduction of cytochrome aa3. However, N2 respiration resulted in only moderate elevation of [K+]o in turtle bran while [K+]o in rat brain was elevated to levels greater than 50 mM. In addition, N2 respiration in turtles had no effect on the rate of recovery of [K+]o, which was elevated by direct electrical stimulation of the brain. Electrocorticographic activity (ECoG) of the turtle brain was only moderately depressed during N2 respiration for up to 4 h whereas the ECoG of rat brain became isoelectric within 1 min. Inhibition of glycolysis with iodoacetate (IAA) resulted in rapid elevation of [K+]o in turtle brain during anoxia, but IAA had little effect on [K+]o during normoxia. These results indicate that the remarkable resistance of the diving turtle to anoxia does not result from continued provision of oxygen to the brain either by redistribution of systemic blood flow or from blood O2 storage. In addition, the turtle brain does not rely on cellular stores of high-energy compounds for maintenance of ionic homeostasis. We conclude that potassium ion homeostasis in the anoxic turtle brain must result from increased glycolytic ATP production and from decreased energy utilization.

Animals↗
PubMed1982

Comparative brain oxygenation and mitochondrial redox activity in turtles and rats.

Comparisons were made between brain oxygenation and cytochrome c oxidase (cytochrome aa3) redox status in turtles (Pseudymys scripta) and rats. Although average brain O2 tension (PtO2) during normoxia was similar in turtle telencephalon and rat parietal cortex, a greater frequency of high and low values of PtO2 occurred in rats, which may indicate a steeper O2 gradient between capillaries and cells. When the fractional inspired O2 concentration (FIO2) was increased, PtO2 was elevated and cytochrome aa3 became more oxidized, whereas decreased FIo2 produced opposite changes in both species. In turtle brain, however, the relationship between PtO2 and cytochrome aa3 redox state was nearly linear over a wide range of PtO2 values. In rats, this relationship was steeper at PtO2 below normoxia and approached a plateau at Pto2 values above normoxia. Turtle brain cytochrome aa3 appeared more reduced in normoxia, which may be due either to lower affinity for O2 or to enhanced substrate supply. These results indicate that differences in resistance to hypoxia/anoxia observed between rats and turtles are probably not due to differences in O2 availability. Rather, it is likely that differences in redox activities of cytochrome aa3 and/or in substrate use play a role in the relative insensitivity of turtle brain to O2 deprivation.

Animals↗
PubMed1981

Local tissue oxygen tension-cytochrome a,a3 redox relationships in rat cerebral cortex in vivo.

Simultaneous measurements were made from rat cerebral cortex, in situ, of focal changes in both tissue oxygen tension (ptO2) and the reduction/oxidation ratio of cytochrome c oxidase (cytochrome a,a3) in order to study relationships between oxygen supply and consumption in small regions of tissue. Local ptO2 was measured with polarographic microelectrodes and the redox state of cytochrome a,a3 with a dual wavelength reflectance spectrophotometer. Increased ptO2, produced by respiration of gas mixtures with elevated O2 and/or CO2 content, was accompanied by increased oxidation of cytochrome a,a3. This confirms that cytochrome oxidase is not fully oxidized in focal brain tissue regions in vivo, as it is in mitochondria isolated in vitro. Decreased ptO2 was accompanied by cytochrome a,a3 reduction. The oxidative changes of cytochrome a,a3 with increases in ptO2 were smaller than the reductive changes associated with decreases in ptO2. Curves relating cytochrome a,a3 redox state to ptO2 were qualitatively alike, regardless of the initial ptO2 value from which they were generated. Thus, the reduction level of cytochrome a,a3 varied with ptO2 on a continuum. This consistent relationship demonstrates that changes in mitochondrial redox state provide an index of relative changes in tissue oxygenation in intact neocortex. The results suggest also that local rates of cerebral oxidative metabolism may not always be constant with changes in local ptO2.

Animals↗
PubMed1981

Oxidative metabolic responses with recurrent seizures in rat cerebral cortex: role of systemic factors.

Simultaneous focal measurements of cerebral oxygen tension and cytochrome a,a3 redox levels were made in rat cortex in order to obtain a direct and continuous assessment of oxidative metabolic changes during serial seizures. Initial seizures evoked by pentylenetetrazol were accompanied by transient increases in tissue pO2 and cytochrome a,a3 oxidation, confirming that oxygen provision is adequate to meet metabolic demand. After some point, subsequent seizures were accompanied by failure of pO2 to increase and failure of cytochrome a,a3 to oxidize, or by decreases in tissue pO2 and shifts in the redox level of cytochrome a,a3 toward reduction, signalling cortical oxygen insufficiency. Whereas early seizures were accompanied by increments in both cerebral blood volume and arterial blood pressure, one or both of these variables failed to increment during later seizures. This was particularly evident following the onset of spontaneously recurring seizures with short intervals between bursts of ECoG activity. These investigations emphasize the importance of systemic factors in determining the cerebral metabolic response to seizures and support the suggestion that neuronal damage in status epilepticus may be the result of derangements of oxidative metabolism.

Animals↗