Ultrasound represents an attractive non-invasive method to assess hemodynamic status. Understanding dynamic changes in hemodynamics in situations such as hypovolemia, sepsis, and cardiogenic shock can potentially help improve patient care. However, the inter-rater reliability and accuracy of how various ultrasound measurements reflect dynamic changes in physiology remains incompletely understood. Overall our aims are to investigate the use of ultrasound in a controlled setting, specifically using lower body negative pressure (LBNP), which can simulate hypovolemia at varied levels in human volunteers.

Aim 1: To determine the change in carotid blood flow (measured by velocity time integral, VTI) in subjects undergoing simulated hypovolemia at LBNP levels that precede vital sign changes.

Hypothesis: Carotid VTI will demonstrate significant changes that precede vital sign changes in simulated hypovolemia.

Aim 2: To compare transcranial color Doppler indices of cerebral blood flow with carotid blood flow, as assessed by VTI of the common carotid artery.

Hypothesis: Changes in transcranial color Doppler indices of cerebral blood flow will be mirrored by changes in carotid blood flow, indicating carotid VTI is an adequate surrogate for measuring cerebral blood flow in variable states of central hypovolemia. However, if cerebral blood flow remains more constant than carotid blood flow throughout varying levels of hypovolemia, our assumption is that cerebral autoregulation alters the relationship between carotid and cerebral blood flow. The more complex procedure of Transcranial Doppler ultrasound (TCD) must be performed to obtain valid assessments of cerebral blood flow.

Study Design: This is a prospective laboratory study using human volunteers.

Study Setting and Subjects: The study will take place in The John B. Pierce Laboratory where volunteers will be subjected to lower body negative pressure using the on-site LBNP chamber.

Protocol: Study subjects will be instructed to refrain from caffeine, alcohol, or cigarettes within 12 hours of the protocol, but will otherwise be allowed their routine oral intake prior to enrollment. The chamber is constructed of a sealed wood and acrylic box that is connected to a vacuum. Subjects will be placed into the chamber, which is sealed to the level of their pelvis by a neoprene skirt. Chamber pressure is transduced to an electronic digital manometer. The pressure in the chamber will reduced rapidly and held for 15-minute intervals at -5, -10, -15, and -20 mm Hg. If the subject becomes lightheaded, nauseated, or does not tolerate the test run in any way; negative pressure will be stopped.

Subjects will be monitored with continuous electrocardiogram monitoring, a standard automated blood pressure cuff, and a noninvasive beat-to-beat hemodynamic monitor (Finometer, Finapres Medical Systems, Amsterdam, The Netherlands). All carotid ultrasound measurements will be performed by specifically trained emergency physicians, using a Philips ultrasound machine (Philips Medical Systems, Andover, MA) equipped with phased and linear array probes programmed with Doppler capability. For transcranial Doppler imaging, we will use a 5- to 1-MHz sector array transducer and an Iu-22 ultrasound system (Philips Healthcare, Best, the Netherlands). Duplex sonography will be performed at the lower end of the frequency range (1-2 MHz) for better sound wave penetration of selected bone windows. For both the common carotid artery and transcranial portion of this study, we will obtain spectral Doppler waveform tracings and record measurements of corresponding vessel diameters. We will use data generated from software analysis of these spectral tracings to calculate hemodynamic parameters of interest to our study. Calculations are based on Bernoulli's principles of fluid dynamics.

Inclusion criteria:

1. Generally healthy
2. Able to provide informed consent
3. Over 18 years of age

Exclusion criteria:

1. Non-English speaking or decisionaly impaired
2. Significant medical illness (as determined by the study physician, JC)
3. Taking vasoactive medications
4. Older than 60 years of age
5. Inability to lie flat for prolonged period
6. Severe claustrophobia
7. Pregnant