PB0429 - Potential difference in platelet aggregation between clinical dexmedetomidine and experimental medetomidine due to dose differences.

Background: Medetomidine and dexmedetomidine share a same feature i.e. adrenalin alpha-2 receptor agonism. The former includes mixture of the latter and its optical isomer, levo-medetomidine. Medetomidine is used for animal anesthesia, and dexmedetomidine for clinical sedation.

Aims: We have compared the platelet aggregating potencies of these two agents using mouse.

Methods: Six months old ICR male mice were anesthetized with pentobarbital (80mg/kg-i.p.). Blood was collected by venipuncture of inferior vena cava with sodium citrate. Platelet rich plasma (PRP) was separated by centrifugating the obtained blood and cells count was adjusted to 25x104/uL. Platelet aggregation induced by collagen (0.5~1.2 ug/mL) or ADP (1~5 uM) was measured by light transmission method using HEMA TRACER (MC-Medical). (1) Medetomidine (100~10,000 ng/mL) or dexmedetomidine (1~100 ng/mL) was added in-vitro to PRP samples 30 minutes before stimulation. (2) Mice were intraperitoneally injected with either dexmedetomidine 10 ug/kg (initial dose in clinical use) or medetomidine 0.75 mg/kg (in MMB-animal anesthesia) before pentobarbital 80 mg/kg anesthesia. Platelet aggregation was evaluated similarly.

Results: (1) The higher concentration of dexmedetomidine 100 ng/mL significantly enhanced collagen 0.5 mg/mL-induced platelet aggregation from 14.8±1.5 % to 71.4±9.8 %, while clinical dosage assuming 10 ng/mL did not (33.8±14.5 %, each n=5). On the other hand, medetomidine 100 ng/mL which assumes animal anesthesia significantly enhanced aggregation (from 15.8±4.1 % to 79.0±3.0 %). (2) In an ex-vivo situation, dexmedetomidine 10 ug/kg-i.p. at clinical dosage did not reveal significant aggregation enhancement (from 14.0±2.0 % to 20.6±12.5 % by collagen 0.5 ug/mL-stimulation) while medetomidine 0.75 mg/kg for animal anesthesia did enhance one (60.7±15.1 %).

Conclusion(s): Dexmedetomidine at clinical use seems not prone to be prothrombotic, while medetomidine in MMB mixed anesthesia for animal experiment enhances platelet aggregation, in comparison with classical pentobarbital anesthesia. Researchers should pay attention when evaluating platelet aggregation data obtained under MMB-anesthesia.