Platelets and artificial surfaces: the effects of drugs.

Contact of blood with a foreign surface activates platelets and leads to their consumption. This property is shared by most non-biological materials, including air, but can be reduced by an optimal balance of hydrophobicity and hydrophilicity, minimal capacity for hydrogen bonding, avoidance of crystallinity, maintenance of polymer backbone mobility, and other manipulations of the chemistry of the polymer. None the less, no totally non-thrombogenic artificial surface has been developed. Attention has therefore turned to suppression of platelet-surface interaction by drugs that alter platelet function. Agents that block cyclo-oxygenase inhibit surface-induced secretion and aggregation but have no effect on platelet adhesion. Drugs that increase platelet cyclic AMP levels have a dose-related effect, which at high concentrations can eliminate adhesion to surfaces. The most successful agent, prostacyclin, has achieved total protection of platelets during cardiopulmonary bypass, with preservation of normal platelet number and function. Associated vasodilatation is a notable side effect, and hypotension may prove to be a significant problem in clinical practice. The development of more selective analogues with minimal vasodepressor activity is to be encouraged.

In vivo assessment in sheep of thromboresistant materials by determination of platelet survival.

The thromboresistance of 13 potentially blood-compatible polymers was assessed in sheep by determining survival of 51Cr-labeled platelets. Polymer tubing (120-150 cm x 2.0-2.3 mm i.d.) coiled around the neck was incorporated into the circulation through silicone rubber connectors as a carotid artery-external jugular vein shunt. The mean platelet half-life in control animals ("shunt control") was 78.2 +/- 2.8 (SEM) hours. Eleven of the 13 polymers tested significantly shortened platelet half-life. Polyvinyl chloride (T1/2 = 45.4 +/- 3.0 hours), polyperfluoro ethylene (T1/2 = 47.0 +/-1.6 hours), and a polymethylacrylate (PMA)/acrilonitrile copolymer (T1/2 = 50.7 +/- 7.0 hours) produced the greatest shortening. Only silica-free polydimethyl siloxane (T1/2 = 74.7 +/- 4.9 hours) and PMA (T1/2 = 81.5 +/- 3.4 hours) were indistinguishable from shunt controls. Pretreatment of PMA tubing with autologous plasma in a paired trial significantly increased platelet half-life (P less than 0.05 vs. untreated PMA). This system offers an economical, reproducible, sensitive, and biologically relevant method for assessment of the reactivity of artificial surfaces with platelets.