The effect on circulating platelet count of repeated intravenous infusions of collagen fibrils was measured in male OFA Sprague-Dawley rats (400-550 g). Citrated blood was pumped from the left carotid artery of anaesthetized animals, via a siliconized double-lumen cannula, into the manifold of a Technicon Autocounter, for continuous registration of platelet count. Native collagen fibrils (Collagenreagent ‘Horm’) were infused intravenously for 1 min at 15 min intervals. Successive increasing collagen doses (20-320 pg/kg) induced dose-dependent reduction in platelet count, measured as absolute platelet number disappearing from the circulation. Repeated infusion of collagen 160 pg/kg produced constant, partially reversible, reduction in platelet count. Several known inhibitors of platelet aggregation were investigated in the described test system. Collagen effects were inhibited in a dose-dependent manner to a maximum of 50-60 %, and drug activity was thus quantitated on the basis of dose producing 30 % inhibition (ID30): prostaglandin E1 (1.6 pg/kg/min i.v. infusion), SH-869 (1.1 mg/kg i.v.), aspirin (33.1 mg/kg p.o.), proquazone, a new non-steroidal antiinflammatory compound (5.0 mg/kg p.o.). That part of the collagen response not inhibited might be attributed to the initial phase of platelet adhesion to collagen, known to be relatively refractive to platelet function inhibitors.
Collagen-Induced Reduction in Rat Circulating Platelet Count: Influence of Platelet Function Inhibitors
