Elevation of plasma histamine levels in the dog following administration of muscle relaxants, opiates and macromolecular polymers

The intensity of the histamine-release phenom-enon, as it occurs following administration of many simple as well as complex compounds, can be estimated by a wide variety of methods (Paton, 1957). The direct chemical measurement of elevations in plasma histamine levels has the advantage of providing a quantitatively uniform basis of comparison which would probably be completely valid if all compounds acted at the same site. However, the basophils and mast cells, forming the chief sites of action, may differ significantly in their relative susceptibility to histamine-releasing drugs and in their facility for releasing histamine into the blood stream. With this recognized limitation, there is yet good reason to determine a scale of comparative elevations of plasma histamine levels which occur following the intravenous injection of clinically useful drugs. In a previous study of this sort (Walton et al., 1959), it was demon-strated that such measurements of foreign colloid reactions in the dog corresponded reason-ably well with the observed hypotensive reactions. With polyvinylpyrrolidone (PVP), acacia, dex-tran, and starch there was decreasing intensity of histamine release as the compounds approached in chemical similarity the body polysaccharide, glycogen. As judged by a survey of the literature describing the clinical experiences with PVP, acacia, and dextran as plasma substitutes, there was a general relation between this laboratory effect and the incidence of their clinically observed allergic-type reactions (Thompson, 1960). It is probable that within a given class of compounds, this measured effect (elevated plasma histamine levels in the dog) may have value in determining the relative incidence potential of this type of reaction in patients. The purpose of the present study is to measure this laboratory effect under uniform conditions following administration of a number of clinically significant compounds. Received for publication July 19, 1963