Effect of a High Concentration Perflubron Emulsion on Platelet Function

Abstract

Perfluorocarbon (PFC) and lipid emulsions (eg. Fluosot®, Intralipia®,) containing phospholipid have been reported to modify platelet function after intravenous infusion. Platelet activation might be responsible for the generation of mediators responsible for PFC-induced side effects. In view of this, we investigated the effect of a highly concentrated perfluorocarbon emulsion, containing 90% (w/v) perfluorooctylbromide (perflubron., PFOB), on porcine and human platelet activation and function. We measured both (1) stimulated ex-vivo porcine platelet aggregation pre and post infusion of either perflubron or control (vehicle only) emulsions and (2) stimulated in vitro human platelet calcium flux in the presence of perflubron emulsion or control emulsions. Platelet aggregation stimulated by collagen, ADP or arachadonic acid (AA) was inhibited in ex-vivo porcine platelets following infusion of perflubron emulsion at a dose of 3 ml/kg (0.2 ml/kg/min). Inhibition was dose-dependent and was decreased when the dose of perflubron emulsion was reduced to 1.0 or 0.3 ml/kg. Infusion of saline or “vehicle” emulsions had little or no effect on stimulated ex-vivo pig platelet aggregation. Fluosol infusion was associated with inconsistent inhibition of platelet aggregation. A23187-or AA-stimulated calcium flux of human platelets in vitro was inhibited in the presence of 1% (v/v) perflubron emulsion. Similar effects were seen with Fluosol, or Intralipid. This inhibition was agonist dose-dependent. We conclude: (1) administration of perflubron emulsion i.v. results in dose-dependent inhibition of stimulant-induced in vitro platelet aggregation, (2) The presence of 1% (v/v) perflubron emulsion inhibits stimulation of platelet calcium flux and (3) perflubron emulsion does not directly activate platelets and thus platelets, and platelet derived mediators (eg. TXA₂), are unlikely to be responsible for the side effects occationally seen following infusion of perfluorocarbon emulsions.