Release of histamine from skin and muscle in the cat by opium alkaloids and other histamine liberators / by W. Feldberg and W.D.M. Paton.

  • Wilhelm Feldberg
Date:
[1951?]
Catalogue details

Licence: In copyright

Credit: Release of histamine from skin and muscle in the cat by opium alkaloids and other histamine liberators / by W. Feldberg and W.D.M. Paton. Source: Wellcome Collection.

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    femoral artery below the origin of the saphenous was ligated and cut, the cannula was tied into the femoral artery above the saphenous, perfusion at once started, and the femoral artery divided above the cannula. Another cannula was tied into the femoral vein in the same way above the saphenous for the collection of the venous effluent. The entirely isolated patch of skin with its cannulated vessels was transferred to a paraffin bath warmed by a water jacket. The skin was spread out with its inner surface upwards on a perforated, immersed, celluloid platform, so that it was possible to observe the washing out of the blood from the perfused parts of the skin, as well as the formation of oedema if it should occur. The paraffin bath used was funnel-shaped, with an outlet at the bottom, so that any fluid escaping from the skin could be collected. It usually amounted to a few ml. only. Warm water was kept circulating through the water jacket near the injection cannula, and through that surrounding the paraffin bath by an ‘air lift’. By this means the temperature of the fluid perfusing the skin and of the paraffin surrounding it was kept at about 37° C. The perfused skin weighed between 15 and 30 g. The perfusion pressure was adjusted so as to maintain a venous outflow of 2-4 ml./min. For this purpose the pressure required ranged between 60 and 200 cm. of water, usually about 100 cm. The histamine content of samples of the skin from the perfused side and corresponding areas on the other limb was determined. The skin was freed from the underlying subcutaneous tissue and, after weighing, cut up in 2 ml. N-HCl/g. skin, and ground in a mortar with sand. This procedure does not fully macerate the tissue. This is achieved as follows: the partly macerated tissue is transferred into another mortar, again cut up and reground after the addition of distilled water (about 10 ml./g. tissue). The contents are returned to the original mortar, again ground and brought into a flask. The mortars are washed several times with saline solution and the washings added to the flask, which is boiled for a minute or two. The flasks are then stored in the cold until the assay is carried out (usually after 24 hr.). For this purpose they are centrifuged or filtered, the residue washed twice with saline solution, the supernatant or the filtrate respectively and the washings mixed, neutralized with N-NaOH, made up to a given, suitable volume and then assayed for histamine on the guinea-pig’s ileum preparation. RESULTS The vaso-depressor action of morphine and codeine in the cat Both morphine and codeine, when injected intravenously, cause a fall in arterial blood pressure. The effect does not start during the first few seconds after the injection, but only appears after a latency of 15-20 sec. which, as shown by Macintosh & Paton (1949), is characteristic for histamine liberators. As seen from Fig. 1, the fall after a large dose of morphine (5 mg.) is steep, whereas after a smaller dose (1 mg.) it develops gradually. Once the blood pressure has fallen after morphine, recovery is either absent or much delayed, even with small doses of morphine. This prolonged action is unlike that of j other histamine liberators. For example, after the injection of 0-5 mg. pro¬ pamidine the immediate depressor action was greater than after 5 mg. of morphine, but the blood pressure was restored within 5 min. After the injection of 5 mg. of morphine, recovery had not set in 45 min. later, when the blood pressure was restored by the intravenous injection of dextran. Large doses of morphine caused stoppage of respiration, so that artificial ventilation was required. After codeine (5 mg.) there were convulsive movements.
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