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Biomedical subjects

M R Murphy

Publications and source records attributed to M R Murphy.

104 records · Page 6Linked to original sources

Tissue redistribution of fentanyl and termination of its effects in rats.

The kinetics of fentanyl elimination from plasma suggest its rapid and extensive uptake by tissues. The authors determined the relationships between tissue and plasma concentrations of fentanyl. Six rats injected iv with 3H-fentanyl citrate (50 micrograms/kg) were sacrificed at each of the following times: 1.5, 5, 15, 30, 60, 120, and 240 min after injection. Tissues were analyzed for unchanged 3H-fentanyl citrate and for total 3H-radioactivity. Fentanyl effects were evident 10 s after injection; recovery began at 5 min and was complete within 60 min. Fentanyl concentrations in brain, heart, and lung equilibrated with that in plasma before 1.5 min and declined at the same rate (t 1/2 alpha = 8 min, t 1/2 beta = 45 min). Fentanyl uptake by muscle and fat was slower and equilibration with plasma occurred by 120 min. Muscle accumulated 56 per cent of the dose within 5 min by which time brain fentanyl levels had declined by 90 per cent. Only 6 per cent of the dose was in fat at 5 min but this increased to a maximum of 17 per cent at 30 min. Fentanyl was extensively metabolized; metabolites represented 25 per cent of body 3H-radioactivity at 15 min, and 80 per cent at 4 h. The authors conclude that the short duration of fentanyl effect is due to its rapid redistribution from sites of action in the brain to sites of storage (muscle and fat) and biotransformation (liver). The elimination of fentanyl from the body is governed by its reuptake from storage sites and its metabolism in the liver. Most of the dose is ultimately excreted in the form of fentanyl metabolites in urine.

Adipose Tissue↗

Pharmacokinetics of 3H-fentanyl in the dog anesthetized with enflurane.

Fentanyl is often used as an anesthetic supplement for short procedures because it has a rapid onset and brief duration of action. However, persistence of ventilatory depression several hours following the last dose has been seen. The authors studied the pharmacokinetics of fentanyl in the dog to find an explanation for the occasionally prolonged duration of action. 3H-fentanyl citrate, 10 or 100 microgram/kg, was injected intravenously in dogs anesthetized with enflurane-O2. Arterial plasma and urine were analyzed for unchanged 3H-fentanyl and for total 3H radioactivity. Kinetic indices were derived by nonlinear least-squares analysis of log concentration (ng/ml) vs. time relationships. Initially, the elimination of fentanyl from plasma was very rapid, and 98 per cent of the amount administered was removed from plasma in the first 5 min after an intravenous injection. However, the terminal elimination phase was prolonged (t1/2 = 199 +/- 17 min). The apparent volume of distribution was large (9.81/kg) and independent of dose. Repetitive doses produced an accumulation of fentanyl. 3H-labelled metabolites of fentanyl were present in the earliest samples of plasma, and accounted for the major portion of the total 3H radioactivity in both plasma and urine. Urine collected for six hours contained 36 per cent of the total 3H radioactivity administered, but only 4 per cent of fentanyl administered was excreted as unchanged fentanyl. The authors conclude that most of a single dose of fentanyl is rapidly eliminated from the body by biotransformation and leads to accumulation of the drug when administered in very large or repeated doses. Under these circumstances the slow release of drug from tissues results in persistent plasma levels of fentanyl and a prolonged duration of action.

Anesthesia, Inhalation↗

Diurnal rhythms of visual accommodation and blink responses: implication for flight-deck visual standards.

The major purpose of this study was to determine whether 24-h variations in accommodation responses occur and, if they do, whether they should be considered in setting visual standards for flight-deck tasks. A recently developed servo-controlled optometer and focus stimulator were used to obtain monocular accommodation response data on four college-age subjects. No 24-h rhythm in accommodation was shown. Heart rate and blink rate also were measured and periodicity analysis showed a mean 24-h rhythm for both; however, blink rate periodograms were significant (p less than or equal to 0.003) for only two of the four subjects. Thus, with the qualifications that college students were tested instead of pilots and that they performed monocular laboratory tasks imstead of binocular flight-deck task, it is concluded that 24-h rhythms in accommodation responses need not be considered in setting visual standards for flight-deck task.

Accommodation, Ocular↗

Olfactory stimulation and olfactory bulb removal: effects on territorial aggression in male Syrian golden hamsters.

The Syrian golden hamster exhibits territorial aggression in a laboratory setting, attacking much more when in the home cage than in the cage of another hamster. In expt. 1 it was found that female hamster vaginal discharge (FHVD) greatly inhibits the territorial aggression of males. In expt. 2 it was found that hamster territorial aggression is almost completely eliminated by bilateral olfactory bulbectomy but is unaffected by unilateral olfactory bulbectomy. However, bilateral olfactory bulbectomized (BOB) hamsters fought back normally if attacked first. Blinding increased the territorial aggression of male hamsters. In expt. 3 a peripheral means of impairing olfaction was used. The results suggest that it is the olfactory impairment, rather than the loss of some hypothetical non-sensory functions of the olfactory bulbs, that causes the elimination of territorial aggression after olfactory bulbectomy. Because of the extensive secondary and tertiary olfactory projections to the limbic forebrain and hypothalamus, and because most laboratory mammals are macro-osmatic, the nature and degree of olfactory control should be an important consideration in studies on the neural basis of social behavior.

Aggression↗

Number of histocompatibility loci in Syrian hamsters.

Syrian hamsters descended from animals captured in the summer of 1971 have been utilized to obtain some estimate of the number of histocompatibility loci in this species. The survival of skin grafts on two F2 populations derived from these animals and two isogenic stocks indicates considerably more histocompatibility loci than previously reported.

Animals↗

Olfactory bulb removal eliminates mating behavior in the male golden hamster.

Mating behavior in sexually naive and sexually experienced male golden hamsters was totally eliminated by removing their olfactory bulbs. In contrast, the mating behavior in blinded, unilaterally bulbectomized, and sham-operated controls was essentially normal. Testosterone injections restored normal sexual behavior in castrated controls but had no effect on the bilaterally bulbectomized animals.

Animals↗