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Biomedical subjects

S Høgskilde

Publications and source records attributed to S Høgskilde.

11 recordsLinked to original sources
PubMed1994

Effects of eltanolone on cerebral blood flow and metabolism in healthy volunteers.

BACKGROUND: Eltanolone is a new steroid anesthetic agent that may prove to be useful in clinical practice. The aim of the present study was to evaluate the effects of eltanolone on cerebral blood flow (CBF) and metabolism in healthy volunteers. METHODS: In a randomized cross-over study, eight subjects received intravenous eltanolone 0.6 mg/kg or its vehicle. CBF was measured with the intravenous xenon 133 technique before and 2 and 30 min after administration of eltanolone or vehicle. Cerebral metabolic rate for oxygen (CMRO2) was calculated as the product of the measured cerebral arteriovenous oxygen content difference and the blood flow. RESULTS: CBF decreased from a baseline value of 64 +/- 4 (mean +/- SD) to 42 +/- 6 ml.100 g-1.min-1 at 2 min after administration of eltanolone and only 4% after vehicle. Cerebral oxygen consumption was 4.1 +/- 0.4 ml.100 g-1.min-1 at baseline and decreased to 2.7 +/- 0.6 at 2 min after eltanolone, whereas metabolism did not change significantly after administration of vehicle. At 30 min CBF and Cerebral metabolic rate for oxygen were 16 and 10% less than baseline values, respectively. Coupling between CBF and Cerebral metabolic rate for oxygen was preserved at all measurements. After administration of eltanolone a significant decrease in mean arterial blood pressure of 6 mmHg and a period of hypoventilation were observed. This did not occur after injection of vehicle. CONCLUSIONS: Eltanolone was shown to reduce cerebral oxygen consumption and blood flow in healthy volunteers. Coupling between metabolism and flow was preserved.

Adult↗
PubMed1994

Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans.

Eltanolone, a new intravenous steroid anaesthetic agent was administered intravenously in a dose of 0.6 mg.kg-1 over 45 s to eight healthy male volunteers to evaluate some of its pharmacokinetic and pharmacodynamic effects. Drug concentration-time data were analysed by PCNONLIN, a non-linear regression programme, showing data consistent with a three-compartment model with initial distribution half-life t1/2 lambda 1 between 0.3 and 2 min, intermediate distribution half-life t1/2 lambda 2 between 12 and 29 min and terminal half-life t1/2 lambda z between 72 and 212 min. The total body clearance of eltanolone was rapid and with individual values in the range 1.6-2.3 l.h-1.kg-1. Eltanolone was initially distributed into a relatively large central compartment V1 between 0.09 and 0.98 l.kg-1 and then extensively further distributed (Vss between 1.80 and 5.44 l.kg-1 and V between 4.87 and 11.87 l.kg-1). The excretion of unchanged of eltanolone in urine was very small, the renal clearance was less than 0.5% of the total clearance. Induction of anaesthesia was trouble free with onset and duration of anaesthesia between 1-2 min and 6-13 min, respectively. There was slight respiratory depression, a small transient increase in heart rate, and a maximum reduction in arterial blood pressure of 23%, as compared with the resting level. Pain on injection and venous sequelae were not seen. Involuntary movements were seen in one subject. We conclude that eltanolone has a favourable pharmacokinetic profile with relatively rapid half-lives, large distribution volumes and rapid total body clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Cardiovascular effects of pregnanolone emulsion: an experimental study in artificially ventilated dogs.

The acute cardiovascular effects of pregnanolone emulsion, a new steroid preparation for intravenous anaesthesia, were investigated in artificially ventilated dogs. The anaesthetic was administered as repeated intravenous bolus injections, doubling the dosage with each injection. The plasma concentration of pregnanolone, and the haemodynamic, respiratory and metabolic variables were determined after each injection. Cardiac output and heart rate increased from the first bolus dose of the anaesthetic (0.5 mg/kg), which produced anaesthesia lasting 10 to 15 min. Both continued to increase after administration of 1.0, 2.0 and 4 mg/kg, whereas reductions of systemic arterial pressure and estimated myocardial contractility were observed only at the two highest dosages. A decrease in vascular resistance was calculated in the systemic circulation, whereas vascular resistance increased in the pulmonary circulation. A state of circulatory shock followed administration 8, 16 and 32 mg/kg of the anaesthetic.

Anesthesia, Intravenous↗
PubMed1991

Dopamine and dobutamine reduce myocardial d-propoxyphene content in experimentally intoxicated rats.

The effect of sympathomimetic intervention with dopamine or dobutamine on the myocardial uptake of d-propoxyphene was investigated experimentally in rats. The d-propoxyphene (19 mg kg-1 h-1) was continuously infused, intravenously, over 45 min. After 20 min of infusion the rats were given either dopamine (12.5 micrograms kg-1 min-1 or 25 micrograms kg-1 min-1), dobutamine (25 micrograms kg-1 min-1 or 45 micrograms kg-1 min-1) or normal saline (control). Each group consisted of eight rats. The myocardial d-propoxyphene content was significantly lower in the two groups given dopamine and in the group given dobutamine 45 micrograms kg-1 min-1 than in the control group (P less than 0.05). This finding indicates the benefit of early sympathomimetic intervention with either dopamine or dobutamine in d-propoxyphene intoxication.

Animals↗
PubMed1990

Pregnanolone emulsion. A preliminary pharmacokinetic and pharmacodynamic study of a new intravenous anaesthetic agent.

Pregnanolone emulsion, a new steroid anaesthetic agent, was administered intravenously as bolus doses to six young healthy male volunteers in a preliminary pharmacokinetic and pharmacodynamic study. The plasma concentration-time curves fitted a two-compartment model. The elimination half-life was between 0.9 and 1.4 hours, volume of central compartment between 0.95 and 2.10 litres/kg, volume of distribution between 3.75 and 5.58 litres/kg and total body clearance between 1.80 and 3.07 (litres/hour)/kg. The excretion in urine of unchanged pregnanolone was less than 0.1%. The pharmacodynamic properties were found to be similar to those of Althesin, with immediate induction of anaesthesia of short duration. The anaesthetic affected haemodynamics only slightly; minor depression of ventilation, with an increase in PaCO2, occurred in several of the subjects. Excitation of short duration occurred in one subject during induction of sleep and slight involuntary muscle movements in another subject during sleep. It is impossible to draw any clear conclusions of the clinical efficacy and tolerance from this limited normal subject trial, but pregnanolone emulsion seems worthy of further clinical trial.

Anesthesia Recovery Period↗
PubMed1988

Anticonvulsive properties of pregnanolone emulsion compared with althesin and thiopentone in mice.

The anticonvulsive properties of pregnanolone (as an emulsion) were evaluated in mice and compared with similar properties of Althesin and thiopentone. Pregnanolone emulsion was found to antagonize convulsions induced by the GABA antagonists pentetrazole, bicuculline and picrotoxin and by the specific glycine receptor antagonist, strychnine. The drug was effective in all four convulsive tests at subanaesthetic doses with maximal activity appearing within less than 1 min. The anticonvulsive therapeutic indices of pregnanolone emulsion were superior when compared with the therapeutic indices of Althesin and thiopentone in all four tests. Pregnanolone emulsion might be a useful alternative drug in the management of convulsive states resistant to conventional therapy.

Alfaxalone Alfadolone Mixture↗
PubMed1987

Pregnanolone emulsion. A new steroid preparation for intravenous anaesthesia: an experimental study in mice.

The anaesthetic activity of pregnanolone (a metabolite of progesterone) in emulsion formulation administered intravenously to male mice was compared with that of Althesin. The loss of righting reflex for 15 seconds was used to estimate the anaesthetic effect. The mean anaesthetic dose (AD50) for the pregnanolone emulsion was 5.25 mg/kg and for Althesin, 2.8 mg/kg. The mean lethal dose (LD50) was 44 mg/kg for pregnanolone and 54 mg/kg for Althesin. The sleeping time after pregnanolone was 2.5-3.5 times longer than after Althesin in dosages above 7.5 mg/kg. No signs of pain or local reaction from injection were observed for either of the drugs. The onset of action was fast for both drugs, with only minor signs of excitation, and recovery was rapid and without excitation. The results indicate that the anaesthetic properties of pregnanolone emulsion are very similar to those of Althesin. Further studies will show whether it can fill the major vacuum left in anaesthetic practice after the withdrawal of Althesin.

Alfaxalone Alfadolone Mixture↗
PubMed1987

Anaesthetic properties of pregnanolone emulsion. A comparison with alphaxolone/alphadolone, propofol, thiopentone and midazolam in a rat model.

The anaesthetic properties of pregnanolone emulsion, a new steroid preparation for intravenous administration, were evaluated in rats and compared to those of Althesin, propofol, thiopentone and midazolam. The therapeutic index was found to be 50% higher than that of Althesin and 6-8 times higher than those of propofol, thiopentone and midazolam. Induction with pregnanolone emulsion was reliable and fast, with only minor excitatory side effects, although induction time was longer compared to Althesin, propofol and thiopentone. Movement of unstimulated rats during sleep was similar to that seen with Althesin but movement on painful stimulation was less than with propofol and thiopentone. Recovery was rapid and smooth, and the proportion of sleeping time to recovery time was higher than found for the other four anaesthetics. No cumulative effects were seen on repeated administration and there were no venous sequelae. The results indicate that pregnanolone emulsion may provide a short-acting, less cumulative and less toxic alternative to existing intravenous anaesthetic agents.

Alfaxalone Alfadolone Mixture↗
PubMed1987

The anticonvulsive activity and toxicity of diazepam in three different formulations. An experimental study in mice.

The anticonvulsive activity (ED50), acute toxicity (LD50), and minimal neurotoxicity (TD50) of diazepam in an emulsion form (Diazemuls) were compared with two different water-based diazepam solutions (Valium and Stesolid). The diazepam preparations were administered intravenously to male mice. After determination of time of peak drug activity, the ED50's were established against pentetrazol-induced convulsions, at peak drug activity. The most important difference between the three diazepam preparations was a significantly higher LD50 of diazemuls (275 mg/kg) compared to valium (49 mg/kg) and stesolid (51 mg/kg). ED50 was: diazemuls 0.24 mg/kg, valium 0.14 mg/kg and stesolid 0.10 mg/kg. The therapeutic indices (LD50/ED50) were thus calculated to be 1146 for diazemuls, 350 for valium and 510 for stesolid. Time of peak drug activity and TD50 were equal for all three drugs. No signs of pain on injection or necrosis were observed following diazemuls, whereas this was common after valium and stesolid.

Animals↗
PubMed1987

Intravenous infusion of Diazemuls in the control of status-like epileptic seizures of different etiology.

This report concerns three patients in whom continuous intravenous infusion of Diazemuls (diazepam dissolved in soya bean oil and emulsified) diluted in 5.5% glucose was used for the controlling of epileptic seizures (status). Diazemuls infusion was effective in one patient with complex partial status epilepticus; in another patient with convulsion secondary to a brain stem infarct, the convulsions were abolished; while only reduced jerking was achieved in the third patient suffering from myoclonic jerks caused by anoxic brain damage. Infusion time ranged from 15 to 33 h. The serum concentrations of diazepam obtained during the infusions were higher than recommended in the literature for treatment of status epilepticus, but could not be correlated to either clinical efficacy or infusion rate.

Aged↗