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Species variation in the heparin contaminant mediated generation of kallikrein
Author(s) -
Myers Lauren,
Hoppensteadt Debra,
McGeehan Elizabeth,
Iqbal Omer,
Adiguzal Cafer,
Cunanan Josephine,
Clark Melanie,
Fareed Jawed
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.569.14
Subject(s) - kallikrein , heparin , chemistry , chondroitin sulfate , prekallikrein , glycosaminoglycan , chondroitin , biochemistry , pharmacology , biology , enzyme
Adverse reactions associated with contaminated heparins are attributed to excess generation of kallikrein due to the presence of oversulfated chondroitin sulfate (OSCS). Contaminated heparins contained up to 30% OSCS on a weight basis. The hypotensive effects of contaminated heparin and OSCS were species dependent. To further investigate variations in contaminant mediated generation of kallikrein, citrated plasma from humans, dogs, rats, cows, rabbits, and monkeys was supplemented with contaminated heparin (CH), contaminant free heparin (CFH), isolated heparin contaminant (HC) and hemisynthetic hypersulfated chondroitin sulfates (HCS‐1 and HCS‐2). In human plasma all agents produced varying degrees of concentration dependent generation of kallikrein (0.3‐0.7/15mins). The generation of kallikrein was found to be high in dog plasma (0.27 to 0.65/15mins), but relatively weaker in monkey (0.13 to 0.36/15mins) and rat plasmas (0.12 to 0.18/15mins). No activation of prekallikrein was noted in cow plasma. The rank order for kallikrein activation was HC > HCS preparations > CH. CFH showed the least activity. These variations in the activation of the contact system in different species may be responsible for the differences in the observed hemostatic and vascular responses. These observations should be considered while screening the effects of drugs and agents with vasoactive actions.