The study aims to describe hemodynamic effects of lower body negative pressure (LBNP).

1. If and how changes in cerebral oxygen saturation (StO2) measured by near infrared spectroscopy (NIRS) relate to changes in blood flow in the carotid arteries during progressive LBNP.
2. If and how mean systemic filling pressure (MSFP) can be measured by brief occlusion of blood flow to an arm and if this relates to LBNP-level.
3. If and how pulse pressure variations and photoplethysmographic amplitude variations during positive expiratory pressure (PEP) and continuous positive airway pressure (CPAP) relate to LBNP-level.

20 healthy volunteers will be included. The study protocol consists of two parts.

1. LBNP is applied stepwise (20 mmHg increments). At each LBNP-level, after 2 min stabilization, blood flow in internal and external carotid arteries is measured. Thereafter, MSFP is measured. LBNP is applied to -80 mmHg, but terminated sooner if the subject experiences signs of decompensation.

   Changes in cerebral StO2 will be related to relative changes in blood flow in the carotid arteries. After these measurements, blood flow to one arm will be occluded for 30 s. Venous pressure measured in an antecubital vein approximates MSFP. This will be related to volume status (LBNP-level and stroke volume reduction).

2. LBNP is applied stepwise (20 mmHg increments). At each LBNP-level, after 2 min stabilization, PEP and CPAP are applied at 0, 5 and 10 cmH20. LBNP is applied to -80 mmHg, but terminated sooner if the subject experiences signs of decompensation.

Flow in carotid arteries is measured by ultrasound/Doppler. Skin blood flow in the forehead measured by laser Doppler flowmetry and transcutaneous oxygen saturation.

If possible, blood flow velocity in a. cerebri media will be measured by transcranial Doppler.

Central venous pressure will be approximated by measuring pressure in the left subclavian vein ("half-way" catheter).

Cardiac stroke volume will be measured by suprasternal Doppler. Expiratory carbon dioxide (CO2) will be measured and recorded. Acral skin photoplethysmography performed using proprietary and custom-made photoplethysmographs.

Arterial blood pressure approximated by finger volume-clamp method.

The measurements above will be used for analyses of possible physiological mechanisms and post-hoc analyses.

Inclusion Criteria:

• Healthy volunteer (informed consent)

Exclusion Criteria:

• Disease/physical condition limiting normal physical activity or requiring medication (except allergies/contraceptives)
• History of syncope (except with obvious vasovagal etiology)
• Cardiac arrhythmia
• Pregnancy
• Skin infections in the elbow crease