The Effect of Local Anaesthetics and Antiarrhythmic Agents on the Responses of Rabbit Platelets to ADP and Thrombin

Abstract

SummaryLocal anaesthetics and antiarrhythmic agents produced changes in responses of rabbit platelets to ADP and thrombin that varied with the agent and its concentration. In high concentrations all local anaesthetics decreased aggregation rates. At lower concentrations several local anaesthetics increased aggregation rates. Depending on the agonist and local anaesthetic, increases were produced at all or only at low or high agonist concentrations. Local anaesthetics failed to influence shape change except at concentrations much greater than those which inhibited aggregation. Inhibition of aggregation by procaine was potentiated by small organic anions suggesting effects at different sites on the platelet membrane. The inhibitory effect of local anaesthetics was decreased by increasing Ca. Kinetic analysis indicated different mechanisms for this Ca effect, i. e., predominantly competitive for procaine or lidocaine and predominantly non-competitive for tetracaine or ethyl lidocaine. Local anaesthetics may affect aggregation by modifying the participation of Ca in this process.

Cocaine-induced platelet defects.

“…19 On the other hand, it has been shown that cocaine enhances the response of rabbit platelets to arachidonic acid, possibly potentiating thromboxane generation and platelet aggregation. 20 In view of these conflicting reports, a critical analysis of the effect of various concentrations of cocaine on human platelet activation and aggregation is needed.…”

Platelet Responsiveness and Biosynthesis of Thromboxane and Prostacyclin in Response to in vitro Cocaine Treatment

“…Moreover, these inhibitory properties, in addition to the recognized capability of local anaesthetics to influence the distribution of Ca++ in a variety of tissue membranes [7,20,21] including platelets [1], could also be due to the capability of these drugs, at high doses, to displace Ca++ from the membrane [2] or to block the Ca++ influx into the platelets [1].…”

“…Local anaesthetics inhibit platelet aggrega tion and the secretion of contents of platelet storage granules elicited by ADP, thrombin, collagen and the Ca++ ionophore A 23187 [ 1,2]. With regard to cocaine, it has also been demonstrated by O'Brien in 1962 [3,4], Aledort andNiemetz in 1968 [5] and Geerdink et al in 1972 [6] that, at high doses, the drug inhibits rabbit platelet aggregation induced by ADP and thrombin, in vitro.…”

“…Recently, Anderson et al [2] showed that lidocaine and tetracaine produced a biphasic change, related to the concentration assayed of rabbit platelet aggregation induced by ADP and thrombin: low concentrations of anaesthetic induced an increase in the plate let aggregation rate, while high concentra tions caused its decrease. The authors hy pothesized that the stimulating as well as the inhibitory effects of these drugs could be related to changes in membrane calcium binding [5,7], Local anaesthetics at high con centrations can displace calcium from the membrane but low concentrations can in crease the calcium binding [2].…”

“…The authors hy pothesized that the stimulating as well as the inhibitory effects of these drugs could be related to changes in membrane calcium binding [5,7], Local anaesthetics at high con centrations can displace calcium from the membrane but low concentrations can in crease the calcium binding [2].…”