Observations On the Effects of Histamine and Serotonin in the Rabbit Ear Chamber

Abstract

Experimental inj ections of histamine can produce increased vascular permeability and vasomotor changes resembling those seen very early in certain acute inflammatory reactions,. 1, '' Moreover, there is evidence that histamine release is involved in the pathogenesis of the earliest phase of some types of acute inflammatory reaction. 3-6 In contrast, there is little to support a role for histamine in the pathogenesis of the later stages of inflammation in which leukocytic sticking and emigration are prominent features. The extent to which histamine can induce sticking and emigration of leukocytes under experimental conditions is unclear.Serotonin is known to have permeability-increasing effects in rats and mice, animals in which histamine is relatively ineffective.7 Conversely, serotonin lacks these effects in other, more histamine-sensitive animals (e.g., rabbits).In the present experiments, the effects of histamine and serotonin upon the microcirculation have been observed directly in an improved rabbit ear chamber. This technique affords a dynamic view of the reactions resulting from these substances, revealing especially the temporal relationships between the various components of the reactions. MATERIALS AND METHODSRabbit ear chamber. The rabbit ear chamber used in our laboratory has been described previously.8 A further modification of the Sandison-Clark chamber,°~ 1° it incorporates two features which permit the observation of very early inflammatory changes. One is a valve through which substances can be injected onto the tissue with negligible trauma, an innovation originally proposed by Sanders.ll The other is the greater thickness of the tissue over the chamber table (70-100 0), affording greater stability so that repeated injections and comparisons of the effects of various substances can be made in the same chamber.Each test material was injected through the valve into the chamber with the aid of a syringe microburet by a method previously described.8 Microscopic observations were made at 2, 5, 10, 20, 30, 45, 60, 90, and 120 min. after injection. In some experiments, further observations were made after 120 min. The method of recording the observations has been described.8 The number of leukocytes &dquo;rolling&dquo; and &dquo;sticking&dquo; in each of two preselected venular segments was recorded. A cell moving along the venular endothelium at a rate slower than that of the axial stream of the venule was said to be &dquo;rolling.&dquo; A cell firmly adherent to the endothelium was said to be &dquo;sticking.&dquo; Numbers of roll-