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R F Hellon

Publications and source records attributed to R F Hellon.

66 records · Page 4Linked to original sources

Observations on the mechanism of salicylate-induced antipyresis.

1. Fever has been produced in conscious rabbits, first, by injection of leucocyte pyrogen into the lateral cerebral ventricle and, second, by local cooling of the hypothalamus.2. Both intravenous and intraventricular salicylate produce antipyresis during an established fever due to intraventricular leucocyte pyrogen. This is incompatible with the hypothesis that salicylate acts by interfering with the passage of leucocyte pyrogen from the circulation into the hypothalamus.3. Intravenous sodium salicylate has no effect on the fever due to local cooling of the hypothalamus. This suggests that salicylates do not act on central or peripheral efferent pathways involved in thermoregulation.

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Temperature effects produced in dogs and monkeys by injections of monoamines and related substances into the third ventricle.

1. In dogs the effects on rectal temperature of noradrenaline, adrenaline, 5-hydroxytryptamine (5-HT) and of the monoamine oxidase inhibitor tranylcypromine were studied following their injection into the third ventricle through a chronically implanted cannula. Tranylcypromine was given also by the intraperitoneal route.2. The hypothermic effect of the catecholamines and the hyperthermic effect of 5-HT previously demonstrated in anaesthetized dogs were obtained also in an unanaesthetized dog, but 5-HT was effective only in doses under 20 mug.3. Tranylcypromine (1 mg) injected into the third ventricle of dogs anaesthetized with pentobarbitone sodium produced shivering and a rise in temperature.4. Tranylcypromine (10 mg/kg) injected intraperitoneally caused a rise in temperature in the unanaesthetized dog. For a time shivering and panting, two effects which produce opposite change in temperature, were observed together. When injected shortly before an intraperitoneal injection of an anaesthetizing dose of pentobarbitone sodium, tranylcypromine not only prevented the fall in temperature which is normally produced by the anaesthetic but caused a greater and longer lasting rise than when given alone.5. The intraperitoneal injections of tranylcypromine produced profuse salivation, a peripheral effect which persisted after acute denervation and which was not abolished by atropine or tolazoline.6. In rhesus monkeys anaesthetized with intraperitoneal pentobarbitone sodium, noradrenaline, adrenaline, 5-HT and 5-hydroxytryptophan (5-HTP) were injected into the cannulated third ventricle. The catecholamines caused a fall in rectal temperature. No evidence was obtained that the fall resulted from a rise in hypothalamic temperature. The injections of 5-HT or of its precursor 5-HTP raised rectal temperature. Monkeys thus respond to the monoamines injected intraventricularly, in the same way as cats and dogs, and unlike rabbits, sheep, goats, oxen and rats.

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Thermal stimulation of hypothalamic neurones in unanaesthetized rabbits.

1. A technique has been devised for recording unit activity in the anterior hypothalamus of conscious rabbits during the controlled displacement of local temperature by 1-2 degrees C. The region at 1 and 2 mm from the mid line was explored.2. All the units studied showed spontaneous activity before thermal stimulation with a mean rate of 9 impulses/sec (range 1/16 sec to 65/sec).3. Twenty-seven (10%) of the recorded neurones showed a change in firing rate which could be related to the temperature changes. Twenty-one of the cells were ;warm-sensitive' and were excited when temperature was raised or inhibited when it was lowered. The other six units were ;cold-sensitive' and showed the opposite type of response.4. Apart from this directional grouping, it was possible to classify the responses into four categories: A, five cells whose firing rate was always proportional to local temperature over a range from 2 degrees C below to 2 degrees C above body temperature; B, six cells whose average level of firing changed during the period of observation, but whose sensitivity to temperature was not affected; C, eight cells which showed a threshold and were only affected by temperature above or below a certain level; D, four cells whose changes in frequency either led or lagged behind the temperature changes.5. The positions of these sensitive units in the hypothalamus did not show any apparent pattern, except that 75% of them were found 1 mm lateral to the mid line; the remaining 25% were 2 mm lateral.

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Effects on temperature of monoamines injected into the cerebral ventricles of anaesthetized dogs.

1. In dogs anaesthetized with pentobarbitone sodium an injection of adrenaline or noradrenaline into the cerebral ventricles through a cannula implanted into the left lateral ventricle caused a fall in rectal temperature as a result of cessation of shivering, loss of muscle tone, and skin vasodilatation. 5-Hydroxytryptamine (5-HT) similarly applied caused shivering and a rise in rectal temperature.2. The hypothalamus of the dog thus appears to react to the three monoamines in the same way as in the cat, and not as in the rabbit and sheep.

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Is prostaglandin E the neural mediator of the febrile response? The case against a proven obligatory role.

We have reviewed the evidence in favor of a prostaglandin mediator of the thermal responses in fever and found that PGE injected into the hypothalamus does not always cause fever, that cerebrospinal fluid concentrations of PGE are not reliable reflections of hypothalamic events, and that antipyretic drugs may act in ways other than inhibiting PGE synthesis. Fever is not blocked by prostaglandin antagonists, nor by ablation of PGE-sensitive areas of the brain. There is poor correlation between the effects of pyrogens and of PGE on cerebral neurons. There is evidence that at least one prostanoid other than prostaglandin is a mediator of fever, but the prostanoid has not been identified yet. We conclude that PGE may contribute to the neural responses in fever but is not essential.

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Are single-unit recordings useful in understanding thermoregulation?

The data which have emerged from single-unit recordings of thermally sensitive neurons in the hypothalamus are reviewed. Although these neurons may be important components in the central control of body temperature, the interpretation of the data is fraught with uncertainties. The neurons in question could be primary thermosensors or part of an integrative network. There is a notable lack of control data to show that thermosensitivity is peculiar to the hypothalamus. Examples are given to show how the single-unit recording technique can be used successfully for tracing thermal information passing centrally from the skin.

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