Ticagrelor in Human Endotoxemia Response to Human Endotoxemia

Inclusion criteria

• Age ≥ 18 and ≤ 35 years
• Male
• No known current medical/psychiatric diseases

Exclusion criteria

• History, signs or symptoms of any cardiovascular disease
• History of chronic obstructive pulmonary disease (COPD) or asthma
• History of hemorrhagic diathesis, or any other disorder associated with increased risk of bleeding
• Previous spontaneous vagal collapse
• Use of any medication
• Smoking
• Liver enzyme abnormalities (defined as ALAT and/or ASAT > twice upper limit of normality)
• Thrombocytopenia (<150*109

/ml) or anemia (haemoglobin < 8.0 mmol/L)

• Any obvious disease associated with immune deficiency
• Febrile illness in the week before the LPS challenge
• Hypersensitivity to ticagrelor or any excipients
• Active pathological bleeding
• History of intracranial haemorrhage
• History of dyspepsia
• quantitative bleeding assessment tool (BAT) score >3 (see Appendix 1)
• Participation in another drug trial or donation of blood 3 months prior, until 3 months after the planned LPS challenge
• Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block, third degree atrioventricular block or a complex bundle branch block
• Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
• Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
• Renal impairment (defined as MDRD < 60 ml/min)