Antihypoxic Drugs Research Articles

Metabolic correction of polyorgan failure in the early stage of traumatic toxicosis

The development of hepatorenal syndrome and endotoxicosis in severe compression trauma is revewed in the article. The main attention is paid to prevention of organ pathology in traumatic toxicosis by means of antihypoxic drugs. The perspectives of succinate-containing antihypoxants for the correction of functional and metabolic activity of the liver in traumatic toxicosis are observed.

Effects of Chinese herbal monomers on oxidative phosphorylation and membrane potential in cerebral mitochondria isolated from hypoxia-exposed rats in vitro.

Mitochondrial dysfunction is the key pathogenic mechanism of cerebral injury induced by high-altitude hypoxia. Some Chinese herbal monomers may exert anti-hypoxic effects through enhancing the efficiency of oxidative phosphorylation. In this study, effects of 10 kinds of Chinese herbal monomers on mitochondrial respiration and membrane potential of cerebral mitochondria isolated from hypoxia-exposed rats in vitro were investigated to screen anti-hypoxic drugs. Rats were exposed to a low-pressure environment of 405.35 mm Hg (54.04 kPa) for 3 days to establish high-altitude hypoxic models. Cerebral mitochondria were isolated and treated with different concentrations of Chinese herbal monomers (sinomenine, silymarin, glycyrrhizic acid, baicalin, quercetin, ginkgolide B, saffron, piperine, ginsenoside Rg1 and oxymatrine) for 5 minutes in vitro. Mitochondrial oxygen consumption and membrane potential were measured using a Clark oxygen electrode and the rhodamine 123 fluorescence analysis method, respectively. Hypoxic exposure significantly decreased the state 3 respiratory rate, respiratory control rate and mitochondrial membrane potential, and significantly increased the state 4 respiratory rate. Treatment with saffron, ginsenoside Rg1 and oxymatrine increased the respiratory control rate in cerebral mitochondria isolated from hypoxia-exposed rats in dose-dependent manners in vitro, while ginsenoside Rg1, piperine and oxymatrine significantly increased the mitochondrial membrane potential in cerebral mitochondria from hypoxia-exposed rats. The Chinese herbal monomers saffron, ginsenoside Rg1, piperine and oxymatrine could thus improve cerebral mitochondrial disorders in oxidative phosphorylation induced by hypobaric hypoxia exposure in vitro.

Acceptability of blood and blood substitutes

Alternatives to donor blood have been developed in part to meet increasing demand. However, new biotechnologies are often associated with increased perceptions of risk and low acceptance. This paper reviews developments of alternatives and presents data, from a field-based experiment in the UK and Holland, on the risks and acceptance of donor blood and alternatives (chemical, genetically modified and bovine). UK groups perceived all substitutes as riskier than the Dutch. There is a negative association between perceived risk and acceptability. Solutions to increasing acceptance are discussed in terms of implicit attitudes, product naming and emotional responses.

Disturbances in energy metabolism during traumatic shock and their pharmacological correction.

In compression traumatic shock caused by mechanical crushing of the lower limbs and eventuating in death of 80% animals, hemodynamic disorders by the end of day 1 lead to the development of energy deficiency most pronounced in skeletal muscles and less pronounced in the liver and kidneys. Energy production in the brain and heart was not impaired. Inhibition of ATP synthesis correlated with decreased SOD activity in organs, but not always with activation of lipid peroxidation, which can occur without concomitant disorders in energy metabolism (in the heart and brain). Therapy with succinate-containing hydroxypyridine derivative decreased animal mortality to 10%; this treatment did not modify hemodynamic parameters, but normalized energy metabolism in organs and activity of the antioxidant and prooxidant systems. These findings suggest that tissue (bioenergetic) hypoxia plays an important role in the pathogenesis of compression traumatic shock and that antihypoxic drugs are essential components of therapy of this condition.

Cerebroprotective drugs shorten the hypoxia-induced onset of electrical silence in unanesthetized rats

Pharmacological agents that delay the hypoxic arrest of neuronal electrical activity, as indicated by the suppression of electroencephalogram (EEG), have previously been thought to increase brain resistance to oxygen insufficiency. On the other hand, acceleration of the EEG suppression may offer some protection against severe hypoxia by reducing neuronal energy spending on electrogenesis. In unanesthetized rats we examined the effects of several antihypoxic drugs on the time of appearance of isoelectric EEG (tiEEG), caused by normobaric hypoxia. In addition, alterations in cerebral blood flow induced by hypoxia and by some drugs were monitored using polarographic techniques to determine if cerebrocirculatory changes play a significant role in the drug effects on tiEEG. We also assessed drug effects on behavioral recovery after hypoxia by measuring the latency of restoration of the head-withdrawal reflex upon vibrissae stimulation. Pentobarbital (30 and 60mgkg−1 i.p.), chloralhydrate (400 mgkg−1i.p.) flunarizine (50–100 mgkg−1p.o.), hydergine (3–50mgkg−1 p.o.), nicergoline (50 mgkg−1and 85mgkg−1 p.o.), sabeluzole (3 and 7.5 mgkg−1i.p.) and vincamine (80 mgkg−1p.o.) reduced tiEEG (mean 27.1 ± 3.3 min prior to drugs). In contrast, idebenone (29–85 mgkg−1p.o.) and vinpocetine (29–85mgkg−1 p.o.) had no significant effects on tiEEG. The divergent effects on cerebral blood flow suggest an insignificant role for cerebrocirculatory changes in the drug-induced reduction of tiEEG during severe hypoxia. The drug effects on recovery of the head-withdrawal reflex (mean 4.2 ± 1.3 min prior to drugs) varied from a delay (sabeluzole) to acceleration (flunarizine) with no correlation to the effects on tiEEG, suggesting that EEG criteria alone may not predict the course of functional recovery.

Efficacy of antihypoxic drugs reducing the affinity of hemoglobin for oxygen in acute cerebral ischemia

Efficacy of antihypoxic drugs reducing the affinity of hemoglobin for oxygen in acute cerebral ischemia

Recovery of normobaric hypoxia-lowered skin conductance repsonse (SCR) in mice: SCR-hypoxia test, an animal model for testing drugs against brain hypoxia

Marcy,Rene, Marie-Anne Quermonne, Josette Raoul and Bounsay Nammathao: Recovery of normobaric hypoxia-lowered skin conductance response (SCR) in mice: SCR-hypoxia test, an animal model for testing drugs against brain hypoxia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1987, 11 : 35–43. 1. 1. SCR-hypoxia test is based on the possible recovery by treatments tested of the SCR depressed through hypoxia. 2. 2. All drugs were administered intraperitoneally to male and female Swiss Orl mice randomized into groups of 10. SCR is measured with a palmar skin conductance-meter, in response to a photostimulus. This apparatus takes place in a cell allowing working in a definite hypoxic atmosphere, at a normal pressure. 3. 3. 15 drugs clinically used in various pathological states related to hypoxia are tested. SCR magnitude is recovered by the “antihypoxic” drugs. 4. 4. Specificity, sensitivity and quantifying value of the test are discussed leading to propose the SCR-hypoxia test in the design of new potentially antihypoxic drugs.