Substances Released from the Skin Following Thermal Injury. I. Histamine and Proteins 1

Abstract

The nature of the substances released from the skin following burning is not known. The majority of the studies concerned with this problem have involved analyses of blood or the lymph draining the burned part, and have been complicated by the complex composition of the blood and lymph and the complex interrelation between different tissues. The present studies represent an attempt to simplify the problem by employing excised skin and collecting the materials diffusing into a saline solution following exposure to hot water. METHODS Preparation of diffusatesMongrel dogs were anesthetized with Nembutalg (30 mg. per kilo) and the skin of their backs was clipped with an Oster No. 40 hair clipper. By the use of an electrically driven dermatome 2 set at .015 inch, split thicknesses of skin 3 3 in. wide and up to 12 in. long were obtained. The slices were placed immediately on salinesoaked gauze, cut up into 3-cm. squares, and secured with the cut surface inward about one end of glass cylinders, 2.4 cm. in diameter (Figure 1). The cut surface was in continuity with the inside of the cylinder. Before the burning, the cut surface was washed three times with 5 to 10 ml. of saline, and after the final washing, 2 ml. of saline were allowed to remain inside of the cylinder. Burning was done in hot water contained in a tray which held a U-shaped metal rack that supported the tubes in such a manner that only the skin was submerged in water ( Figure 2

Rationale of Antihistaminic Therapy in Thermal Injury

“…Jackson, and Lowbury, 1952). This clinical finding is consistent with Lewis's (1927) observation that the triple response elicited by pricking histamine into human skin is also induced by thermal injury, and with the fact that histamine is readily released in vitro by heat from the skin of various species of animal (Rosenthal and Minard, 1939). However, in human volunteers given an oral antihistamine immediately after experimental burns were made, Sevitt et al (1952) could not confirm the clinical findings; and the increased vascular permeability induced by high-temperature burns in rabbits (Weeks and Gunnar, 1949) and by thermal injury in anaesthetized guinea-pigs (Sevitt, 1949) is not antagopized by high doses of antihistamines.…”

“…These drugs are effective in practically the same order as inhibitors of the permeability increase The high susceptibility of the immediate response to small doses of antihistamines suggests that only small amounts of histamine are liberated. This is supported by the low histamine content that we found in intercellular perfusates (Miles and Wilhelm, 1958b) Rosenthal et al, 1957). All the liberatable histamine was, in fact, released at this temperature, because when this heated skin was finely chopped the remaining 80% readily leached into the suspending fluid.…”

Substance P in sensory nerve fibres contributes to the development of oedema in the rat hind paw after thermal injury

“…The release or local formation of several mediators involved in this process have been described, i.e. 5-hydroxytryptamine (5-HT), histamine (Rosenthal et al, 1957, Spector & Willoughby, 1958, kinins including bradykinin (Starr & West, 1967) and prostaglandins E1, E2 and F2C, (Heggers et al, 1980). Vascular protein leakage after stimulation of peripheral nerves is caused by release of a mediator from the peripheral terminals of C-fibre afferents, since it was shown to be abolished after pretreatment of newborn rats with capsaicin, which leads to a selective degeneration of certain populations of sensory C-fibres (Jancs6 et al, 1977).…”

Involvement of sensory neuropeptides in the development of plasma extravasation in rat dorsal skin following thermal injury

“…It is well established that oedema formation is induced by thermal injury, the magnitude of which depends on the temperature and duration of the burn (Saria, 1984;Blomgren & Bagge, 1984). Several mediators have been shown to be involved in the initial inflammatory process, i.e., histamine (Rosenthal et al, 1957), bradykinin, (Rocha e Silva & Rosenthal, 1961;Starr & West, 1967), 5-hydroxytryptamine, prostaglandins (Willis, 1970;Jonsson, 1971;Jonsson et al, 1979;Williams, 1979) and substance P (SP; Saria, 1984;Jonsson et al, 1986). Furthermore, Saria (1984) showed that pretreating neonatal rats with capsaicin to cause selective degeneration of sensory C-fibres significantly inhibited plasma extravasation in the rat hind paw following thermal injury.…”