In vivo and in vitro effects of adrenosem semicarbazone on histamine and bradykinin induced physiological changes

Thesis (M.A.)--Boston UniversityPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Adrenochrome, a red, primary oxidation product of adrenalin, was reported to possess hemostatic properties; however, the life time of adrenochrome, only a few hours, rendered it unsuitable for experimental or clinical use. The monosemicarbazone of adrenochrome proved to be stable but insoluble. By solubalizing the latter compound in sodium salicylate a complex, marketed under the trade name Adrenosem, resulted, which is reported to retain the hemostatic properties of adrenochrome. Clinical investigations of Adrenosem in various types of surgical procedures have indicated that the drug is effective in controlling bleeding and oozing from the small, non-clampable bleeders. Unfortunately, these clinical studies provide no information concerning a mechanism of action. Experimental studies have suggested that Adrenosem controls bleeding by decreasing vascular permeability. If this is indeed the case, then perhaps Adrenosem exerts its reported hemostatic effect by antagonizing compounds known to increase vascular permeability, such as histamine and bradykinin. The possibility was investigated in the present study by means of both an in vivo and an in vitro procedure. The former consisted of measuring the histamine and bradykinin induced increase in vascular permeability of rat skin to circulating, protein bound dye. Rats were pre-treated with Adrenosem,I. M., in order to see if this increase in vascular permeability from a subcutaneous injection of histamine or bradykinin could be diminished. The latter procedure used the in vitro response of uterine and gut smooth muscle to histamine and bradykinin as a test system. A possible inhibition or antagonism of this response was investigated by pretreating the muscle with Adrenosem. From the findings of the present study it appears that the hemostatic effect of ADC if not mediated by the antagonism of histamine or bradykinin. On the contrary, ADS seems to enhance the ability of histamine and bradykinin to increase vascular permeability in rat skin and to relax the smooth muscle of the gut and uterus.2031-01-0