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Biomedical subjects

S Rehncrona

Publications and source records attributed to S Rehncrona.

At least 55 records · Page 3Linked to original sources
PubMed1981

Brain lactic acidosis and ischemic cell damage: 2. Histopathology.

The influence of severe tissue lactic acidosis during incomplete brain ischemia (30 min) on cortex morphology was studied in fasted rats. Production of lactate in the ischemic tissue was varied by preischemic infusions (i.v.) of either a saline or a glucose solution. The brains were fixed by perfusion with glutaraldehyde at 0, 5, or 90 min of recirculation. In saline-infused animals (tissue lactate about 15 mumol g-1), changes observed at 0 and 5 min of recirculation were strikingly discrete: slight condensation of nuclear chromatin, mild to moderate mitochondrial swelling, and only slight astrocyte edema. These changes had virtually disappeared after 90 min recirculation and, at this time, only discrete ribosomal changes were observed. In contrast, glucose-infused rats (tissue lactate about 35 mumol g-1) showed severe changes: marked clumping of nuclear chromatin and cell sap in all cells was already evident at 0 and 5 min recirculation, while mitochondrial swelling was mild to moderate. Although tissue fixation was inadequate at 90 min, the ultrastructural appearance indicated extensive damage. It is concluded that excessive tissue lactic acidosis during brain ischemia exaggerates structural alterations and leads to irreversible cellular damage. A tentative explanation is offered for the paucity (less than 0.2%) of condensed neurons with grossly swollen mitochondria, previously considered a hallmark of ischemic cell injury.

Acidosis↗
PubMed1981

Free fatty acids in the rat brain in moderate and severe hypoxia.

The effects of mild, moderate, and severe hypoxia on cerebral cortical concentrations of free fatty acids (FFAs) were investigated in artificially ventilated rats under nitrous oxide anaesthesia. No change occurred during either mild (arterial PO2 35-40 mm Hg) or moderate (PO2 25-30 mm Hg) hypoxia. The effects of severe hypoxia (PO2 about 20 mm Hg) combined with hypotension (mean arterial blood pressure 80-85 mm Hg) varied with the EEG pattern and the tissue energy state. Thus, a major increase in total as well as in individual FFAs occurred first when EEG was severely depressed (almost isoelectric) and energy homeostasis disrupted. On a relative basis the greatest change occurred in free arachidonic acid. It is concluded tha hypoxia is associated with an increase in the concentrations of FFAs in brain tissue, provided that tissue oxygen deficiency is severe enough to cause tissue energy failure. However, an increase in FFAs does not invariably accompany minor reductions in the adenylate energy charge (EC) of the tissue.

Adenine Nucleotides↗
PubMed1980

The increase in extracellular potassium concentration in the ischemic brain in relation to the preischemic functional activity and cerebral metabolic rate.

The course of ischemic increase of extracellular potassium concentration ([K+]e) was studied in rat cerebral cortex with potassium selective microelectrodes and correlated to the preischemic functional and metabolic state. Complete cerebral ischemia was induced in artificially ventilated rats by cardiac arrest. Seven different functional states including conditions with cerebral hypermetabolism (seizures, amphetamine intoxication, hyperthermia) and hypometabolism (barbiturate anesthesia, hypothermia) were chosen in order to cover a wide range of cerebral metabolic rates (CMRO2 : 28.7--2.4 ml O2/(100 g)/min). The ischemic increase of [K+]e was delayed in conditions with low CMRO2 and accelerated in conditions with high CMRO2; the time interval to the terminal steep rise in extracellular potassium concentration varied within the extremes of 35 +/- 5 and 365 +/- 12 sec (means +/- S.E.M.), the control state (N2O-analgesia) being 116 +/- 5 sec. In groups with high CMRO2 electrocortical activity ceased within 15 sec and in groups with low CMRO2 within 22 sec. The rates of the ischemic [K+]e increase, measured as rate of change in the potassium electrode potential (mV/sec), remained high in conditions with high preischemic CMRO2 and low in conditions with low CMRO2, indicating a remaining influence of the preischemic metabolism on membrane ion permeability. These results support previous metabolic data indicating that the rate of consumption of high energy phosphates during ischemia mirrors the preischemic cerebral metabolic rate. Phenobarbital anesthesia did not change the initial rate of [K+]e increase but reduced the rate of [K+]e increase later during ischemia, suggesting a special effect of barbiturates on partly depolarized membranes.

Adenosine Triphosphate↗
PubMed1980

Neuronal cell damage in the brain: possible involvement of oxidative mechanisms.

Neuronal lesions in the brain occur in conditions associated with a reduced supply of oxygen (hypoxia and ischemia) and glucose (hypoglycemia) as well as in those associated with a pathologically enhanced neuronal activity (status epilepticus). In only two of these conditions (hypoxia and ischemia) are the lesions correlated to cellular oxygen lack, and gross energy failure is absent in one condition (status epilepticus). Although anaerobic mechanisms seem responsible for the cell injury in hypoxia and ischemia, oxidative mechanisms could operate in hypoglycemia and status epilepticus. Since the supply of oxygen has not ceased altogether in hypoxia and incomplete ischemia, and since reoxygenation/recirculation leads to a transient increase in tissue oxygen tensions, one cannot exclude the possibility that oxidative mechanisms contribute to the final damage following all types of cellular oxygen lack. We have failed to obtain evidence that peroxidative degradation of cellular constituents occurs in hypoglycemia and status epilepticus. Thus, there is neither a perturbation of the redox state of the glutathione pool of the tissue nor a measurable degradation of polyenoic phospholipid-bound fatty acids. It is emphasized that the cascade of events triggered by an accumulation of free polyenoic fatty acids, mainly arachidonic acid, may contribute to cell lesions by leading to cell edema and/or microcirculatory changes. During seizures, such an accumulation occurs even though energy failure is moderate and it may conceivably contribute to cell damage. In general, though, mechanisms of cell damage in the brain remain partly elusive.

Animals↗
PubMed1980

Barbiturates as protective agents in brain ischemia and as free radical scavengers in vitro.

Barbiturates protect the brain in several types of ischemia. The exact mechanism(s) by which they afford protection are unknown. Interest has been focused for the most part on their effects as metabolic depressants, but a slowing energy consumption rate in the ischemic brain cannot explain protection in all ischemic situations. Other propositions for the protective mechanisms of barbiturates include alterations in blood flow distribution, membrane stabilization as well as antioxidant and free radical scavenging properties. We have studied the inhibitory effects of various barbiturates on iron- and ascorbic acid-stimulated lipid peroxidation in brain tissue in vitro. While thiopental was highly efficient, other barbiturates had no (phenobarbital, pentobarbital) or only minor (methohexital) inhibitory effects. The findings were confirmed by studies of the scavenging properties of these barbiturates with a different system (1,1 diphenyl-2-picryl hydrazyl). Since all tested barbiturates protect in brain ischemia in vivo, our results do not support the hypothesis that they protect by acting as free radical scavengers.

Animals↗
PubMed1980

Reversible ischemia of the brain: biochemical factors influencing restitution.

Biochemical factors of potential importance for the development of irreversible brain cell damage in reversible ischemia may, at least theoretically, not only involve anaerobic events but also oxidative reactions. If so, such reactions should be expected to occur either if oxygen delivery to the tissue during ischemia is not totally abolished, i.e. as in incomplete ischemia, or during the recirculation phase. Several investigations have shown that pronounced incomplete brain ischemia is more deleterious than complete ischemia. The persistence of some circulation in the former situation may a) allow oxidative reactions to continue at a slow rate b) lead to excessive tissue lactic acidosis by continued supply of substrate for anaerobic glycolysis. Our studies concerning brain tissue concentrations of reduced and oxidized glutathione, fatty acids and phospholipids in reversible, pronounced, incomplete and complete ischemia fail to support the hypothesis that oxidative damage is an important factor for the development of irreversible neuronal damage. On the other hand, our studies have shown that the degree to which lactate accumulates during ischemia is critical for restitution.

Aerobiosis↗
PubMed1979

Influence of chlormethiazole on cerebral blood flow and oxygen consumption in the rat, and its effect on the recovery of cortical energy metabolism after pronounced, incomplete ischaemia.

The influence of an anaesthetic dose of chlormethiazole (Hemineurin) on blood flow (CBF) and oxygen consumption (CMRO2) in the rat brain was investigated. In spontaneously breathing animals a dose of 160 mg . kg-1 of chlormethiazole, infused i.v., induced a state close to surgical anaesthesia. In paralyzed animals, the same dose decreased CBF and CMRO2 to about 60% of control, an effect similar to that observed after an anaesthetic dose of phenobarbitone. Neither a protective nor a detrimental effect of chlormethiazole could be demonstrated when the drug was given during reversible and pronounced, incomplete ischaemia, as evaluated from the postischaemic tissue concentrations of labile phosphates (PCr, ATP, ADP, AMP) and of lactate and pyruvate. It is concluded that protection in this situation (as earlier shown with phenobarbitone) must, at least partly, be related to other mechanisms than a depression of metabolism.

Anesthesia, General↗
PubMed1979

Local versus regional cerebral blood flow in the rat at high (hypoxia) and low (phenobarbital anesthesia) flow rates.

Local cerebral blood flow (CBF) was measured in rats, using an autoradiographic technique with 14C-iodoantipyrine as diffusible tracer, in situations with low, normal and high flow rates (phenobarbital anesthesia, analgesia with 75% N2O, and hypoxia, respectively). A comparison of the results with previous data obtained in conscious rats (Sakurada et al. 1978) demonstrates that 75% N2O moderately reduces local CBF in some, but not all, cortical and subcortical areas, that phenobarbital anesthesia reduces local CBF to between 30 and 65% of (conscious) control, and that pronounced hypoxia (arterial P02 about 25 mmHg) increases local CBF 3- to 4-fold. A comparison of the values obtained for cortical structures with those previously measured with a technique based on the Fick principle shows that the autoradiographic technique gives similar values at low and normal flow rates but that it moderately underestimates CBF at high flow rates, probably due to diffusion limitation.

Anesthesia, General↗
PubMed1979

Cerebral energy state, mitochondrial function, and redox state measurements in transient ischemia.

Earlier results are reviewed suggesting that transient pronounced, incomplete cerebral ischemia could be more deleterious for the recovery of brain tissue energy state than a complete interruption of the blood flow. Measurements of respiratory function of brain mitochondria, isolated after 30 min of either complete or incomplete ischemia, demonstrated a similar inhibition of respiratory activity and maximal phosphorylation rates in both situations. This inhibition was totally normalized during recirculation after complete ischemia while a further deterioration was found after incomplete ischemia. The in vivo alterations of the cortical tissue distribution of redox states during transient, incomplete ischemia (15--60 min) were measured using a flying spot fluorometer, which gives a real-time and on-line display of the tissue distribution of NADH and oxidized flavoprotein. A reoxidation in both systems was demonstrated during the recirculation period and the distribution of redox states showed no further heterogeneity in the postischemic period as compared to the preischemic distribution. It is concluded that reoxygenation of the brain tissue is possible even after long periods of incomplete ischemia. The normal distribution of redox states during recirculation suggests that mechanisms other than an impaired or inhomogeneous oxygen delivery during the postischemic period are responsible for the failure in recovery of mitochondrial function and tissue energy state.

Animals↗