Premium
Dextran‐70 inhibits equine platelet aggregation induced by PAF but not by other agonists
Author(s) -
HEATH M. F.,
EVANS R. J.,
HAYES L. J.
Publication year - 1998
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/j.2042-3306.1998.tb04510.x
Subject(s) - dextran , platelet aggregation , chemistry , platelet , horse , pharmacology , biophysics , medicine , biochemistry , biology , paleontology
Summary Dextrans of mean molecular weight 70 kDa (dextran‐70) have had clinical use as antithrombotics in man. A major part of the anti‐thrombotic action is mediated via inhibition of platelet function. Greatorex (1975, 1977) treated thromboembolic colic in horses with infusions of dextran‐70 and reported a 90% recovery rate, but this treatment is nonetheless rarely used. We have used an in vitro method to examine the effect of dextran‐70 on equine platelet suspensions, in the hope that understanding the mechanism of action of dextran‐70 might lead to the development of alternative therapeutic agents. The effects of dextran‐70 on equine platelets occurred immediately in vitro with an initial activation and shape change. Subsequent assessment of aggregation revealed a dose‐dependent specific inhibition of platelet‐activating factor (PAF)‐induced aggregation, significant in rate of aggregation at dextran‐70 concentrations >40 g/l (P<0.05) and in extent of aggregation at dextran‐70 concentrations >50 g/l (P<0.05). Preincubation with 60 g/l dextran‐70 significantly inhibited the rate and extent of aggregation in response to PAF (1 nmol/l) (P<0.001 and P = 0.003, respectively) but this was not dependent on the duration of pre‐incubation (from 0 to 150 min). No effects were seen when the agonist was adenosine 5′‐diphosphate (200 nmol/l), collagen (10 mg/l), 5‐hydroxytryptamine (100 pmol/l) or 1144069 (600 nmol/l) (all P>0.1). Analysis of PAF concentration‐aggregation curves after pre‐incubation with 60 g/l dextran‐70 indicated significant noncompetitive inhibition by dextran‐70 (P<0.001 for rate and extent of aggregation). The ability of dextran‐70 to inhibit responses of equine platelets to PAF is probably an important component of its beneficial effect as an antithrombotic in colic cases.