Brain blood flow and blood pressure during hypoxia in the epaulette shark Hemiscyllium ocellatum, a hypoxia-tolerant elasmobranch.
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The key to surviving hypoxia is to protect the brain from energy depletion. The epaulette shark (Hemiscyllium ocellatum) is an elasmobranch able to resist energy depletion and to survive hypoxia. Using epi-illumination microscopy in vivo to observe cerebral blood flow velocity on the brain surface, we show that cerebral blood flow in the epaulette shark is unaffected by 2 h of severe hypoxia (0.35 mg O2 l-1 in the respiratory water, 24 C). Thus, the epaulette shark differs from other hypoxia- and anoxia-tolerant species studied: there is no adenosine-mediated increase in cerebral blood flow such as that occurring in freshwater turtles and cyprinid fish. However, blood pressure showed a 50 % decrease in the epaulette shark during hypoxia, indicating that a compensatory cerebral vasodilatation occurs to maintain cerebral blood flow. We observed an increase in cerebral blood flow velocity when superfusing the normoxic brain with adenosine (making sharks the oldest vertebrate group in which this mechanism has been found). The adenosine-induced increase in cerebral blood flow velocity was reduced by the adenosine receptor antagonist aminophylline. Aminophylline had no effect upon the maintenance of cerebral blood flow during hypoxia, however, indicating that adenosine is not involved in maintaining cerebral blood flow in the epaulette shark during hypoxic hypotension. (+info)
Randomised controlled trial of aminophylline for severe acute asthma.
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OBJECTIVES: To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously. STUDY DESIGN: Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol. RESULTS: The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group. CONCLUSIONS: Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment. (+info)
Pharmacokinetics of theophylline metabolites in 8 Chinese patients.
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AIM: To study theophylline metabolites pharmacokinetics in patients after a therapeutic dose. METHODS: Eight adult patients with mild bronchial asthma and normal liver function were infused aminophylline intravenously (6.6 mumol.kg-1). The plasma concentrations of theophylline and its 4 metabolites: 1,3-dimethyluric acid (DMUA), 3-methylxanthine (3-MX), 1-methyluric acid (MUA), and the intermediate 1-methylxanthine (1-MX) were monitored by HPLC throughout 24 h. RESULTS: The plasma concentration of DMUA was the highest one among the 4 metabolites. 3-MX showed the slowest elimination rate. The plasma concentration of 1-MX throughout a 24-h period showed that there was a picking up of 1-MX (from 0.04 mumol.L-1 to 1.05 mumol.L-1) in the next morning. CONCLUSION: The formation of DMUA was the main metabolites. During night there was an accumulation of 1-MX. (+info)
Aminophylline alters the core temperature response to acute hypoxemia in newborn and older guinea pigs.
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In newborns and adults of a number of species, exposure to acute hypoxemia produces a "regulated" decrease in core temperature, the mechanism of which is unknown. The present experiments were carried out on chronically instrumented newborn (5-10 days of age; n = 27) and older (25-30 days of age; n = 23) guinea pigs to test the hypothesis that adenosine mediates this regulated decrease in core temperature. During an experiment, core temperature was measured by biotelemetry from animals studied in a thermocline during a control period of normoxemia, an experimental period of normoxemia or acute hypoxemia (fraction of inspired oxygen 0.10), and during a recovery period of normoxemia after an intraperitoneal injection of 10 mg/kg aminophylline (i.e., a nonspecific adenosine antagonist) or vehicle. Core temperature decreased significantly during hypoxemia after vehicle in both newborn and older guinea pigs. After aminophylline, however, newborn guinea pigs failed to significantly decrease their core temperature, whereas older guinea pigs exhibited an attenuated yet significant core temperature decrease during hypoxemia. Our data support the hypothesis that adenosine plays an age-dependent role in mediating the regulated decrease in core temperature that occurs in newborn and older guinea pigs during acute hypoxemia. (+info)
Adenosine contributes to hypoxia-induced forearm vasodilation in humans.
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In humans, hypoxia leads to increased sympathetic neural outflow to skeletal muscle. However, blood flow increases in the forearm. The mechanism of hypoxia-induced vasodilation is unknown. To test whether hypoxia-induced vasodilation is cholinergically mediated or is due to local release of adenosine, normal subjects were studied before and during acute hypoxia (inspired O(2) 10.5%; approximately 20 min). In experiment I, aminophylline (50-200 microg. min(-1). 100 ml forearm tissue(-1)) was infused into the brachial artery to block adenosine receptors (n = 9). In experiment II, cholinergic vasodilation was blocked by atropine (0.4 mg over 4 min) infused into the brachial artery (n = 8). The responses of forearm blood flow (plethysmography) and forearm vascular resistance to hypoxia in the infused and opposite (control) forearms were compared. During hypoxia (arterial O(2) saturation 77 +/- 2%), minute ventilation and heart rate increased while arterial pressure remained unchanged; forearm blood flow rose by 35 +/- 6% in the control forearm but only by 5 +/- 8% in the aminophylline-treated forearm (P < 0.02). Accordingly, forearm vascular resistance decreased by 29 +/- 5% in the control forearm but only by 9 +/- 6% in the aminophylline-treated forearm (P < 0.02). Atropine did not attenuate forearm vasodilation during hypoxia. These data suggest that adenosine contributes to hypoxia-induced vasodilation, whereas cholinergic vasodilation does not play a role. (+info)
Mutability of different genetic loci in mammalian cells by metabolically activated carcinogenic polycyclic hydrocarbons.
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The relationship between carcinogenesis and mutagenesis in mammalian cells has been determined with 10 polycyclic hydrocarbons with different degrees of carcinogenicity. Mutagenesis was determined in Chinese hamster cells with genetic markers that affect the surface membrane, nucleic-acid synthesis, and protein synthesis. The mutations were characterized by resistance to ouabain, 8-azaguanine, and temperature. Mutagenesis by the carcinogens required metabolic activation and this was provided by the presence of lethally irradiated metabolizing cells. The degree of carcinogenicity was related to the degree of mutagenicity for all three genetic markers. The most potent carcinogen, 7,12-dimethylbenz[a]anthracene, gave the highest mutagenicity and mutagenicity was obtained with 0.01 mug/ml. Treatment of the cells with aminophylline, which increases polycyclic hydrocarbon metabolism, increased mutagenesis by the carcinogens. It is suggested that such an experimental system with these and other mammalian cells should be useful as a sensitive assay for hazardous environmental chemicals. (+info)
Pharmacological properties of some xanthone derivatives.
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A series of aminoalkanolic derivatives of xanthone were examined in some experimental models of epilepsia, i.e., pilocarpine, aminophylline and pentetrazole-induced seizures. A final objective of this research was to examine the action of these compounds on the central nervous system, namely on spontaneous locomotor activity, amphetamine-induced hyperactivity and narcotic sleep induced by hexobarbital, as well as their influence on the gamma-aminobutyric acid (GABA) level and glutamic acid decarboxylase (GAD) activity in mice brain. The most interesting were the pharmacological results of (R)-2-N-methylamino-1-butanol derivative of 7-chloro-2-methylxanthone [Id], which displayed protective activity against the seizures induced by maximum electroshock and pentetrazole induced seizures; moreover, this compound had a relatively low toxicity and did not exhibit a neurotoxic effect. The influence on the locomotor activity as well as on the amphetamine-induced locomotor hyperactivity in mice was also seen for Id. Compound Id did not decrease the GABA level in mice brain. (+info)
Metabolic and respiratory effects of theophylline in the preterm infant.
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BACKGROUND: Methylxanthines are often administered to preterm infants for the treatment of apnoea. AIMS: To study the effects of theophylline on energy metabolism, physical activity, and lung mechanics in preterm infants. METHODS: Indirect calorimetry was performed for six hours before and after administration of a bolus of theophylline (5 mg/kg) in 18 preterm infants while physical activity was recorded with a video camera. Lung mechanics measurements were performed at baseline and 12 and 24 hours after theophylline treatment. RESULTS: Theophylline increased mean (SEM) energy expenditure by 15 (5) kJ/kg/day and augmented carbohydrate utilisation from 6.8 to 8.0 g/kg/day, but fat oxidation was unchanged. After theophylline treatment, preterm infants had faster respiration, lower transcutaneous CO2, and improved static respiratory compliance without increased physical activity. CONCLUSIONS: A bolus of 5 mg/kg theophylline increased energy expenditure independently of physical activity, increased carbohydrate utilisation, and improved respiratory compliance. The increased energy expenditure could be detrimental to the growth of the preterm infant. (+info)