HEART

Abstract: Orthostatic intolerance on return from microgravity is still one of the medical problems most difficult to prevent or predict. This project will include candidate-astronauts and astronauts returning from spaceflight in a larger study geared towards quantifying the response to gravity in adult healthy subjects and patients with disturbances of the autonomic nervous system, who regularly experience orthostatic intolerance. In this we develop a test protocol using non-invasive physiological parameters (e.g. finger blood pressure, transcranial Doppler blood flow velocity). These data are used in multivariate autoregressive parameter estimation to quantify the factors that typify a person's blood pressure control system. In the space-related part of this project we use an elaborate test protocol in candidate astronauts once in our laboratory. This will include orthostatic challenges on a fast tilt table programmed to deliver a series of sinusoidal and random movements covering a broad part of the spectrum. In 2 later pre-flight sessions a conventional tilt table test (supine, 70O head up tilted and tilted back to supine) will be performed. The same test protocol is performed directly after return to earth (R+0) and on days R+1 and R+5. The outcome of the usual postflight stand test is given as the number of minutes (maximum 10) the astronaut can stand relaxed directly after return before presyncopal symptoms appear. This number will be our 'calibration point' to test the validity of our predictions made based on the preflight measurements. The outcome of this experiment is the rejection or confirmation of our prediction on orthostatic (in?)tolerance directly after spaceflight. A good predictor test will help identify those candidate astronauts who need special measures on return to earth, like salt- and water sparing drugs in combination with (salt and) fluid loading. Moreover, in every-day medicine it will help to better identify patients with hidden orthostatic problems that sporadically come to expression under unfavorable circumstances.

Address corresponding author:
Dr. John M. Karemaker, Academic Medical Center, Dept. of Physiology, Univ. of Amsterdam, AMC-M01-08, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Tel +31-20-5664827, Fax: +31-20-6919319, E-mail: j.m.karemaker@amc.uva.nl.

Co-Investigators:
Johannes J. van Lieshout, Wim J. Stok, B.Sc.; Ms. Janneke Gisolf, Med. Drs., Dept. of Physiology, Univ. of Amsterdam, Acad. Med. CenterJ. Philip Saul, MD; SC Children’s Heart Center, Medical University of South Carolina, USA (consultant)
Prof. Philippe Arbeille, MD, PhD, CHU de Trousseau, Tours (Fr.), Co-PI: Pr. Claude Gharib, PhD, Laboratoire de physiologie de l’Environnement, Faculté de Médecine Lyon Grange Blanche, Lyon, FR.

Introduction: Classical techniques to quantify the quality of orthostatic cardiovascular control call for steady state conditions: for instance blood pressure, heart rate and cardiac output, to be measured in supine and upright positions. In the usual scoring of these tests one will look at the changes in systolic/diastolic blood pressure and heart rate with body position. Systolic blood pressure is not supposed to fall more than 20 mmHg in the upright position, diastolic not more than 5-10 mmHg and heart rate should nor rise more than 30 beats per minute ((12)). Even then, one cannot connect these measurements to parameters that give information on specific aspects of the cardiovascular control system. That requires a (computational) model of the circulation to tell how aspects of the physiological responses can be tied to relevant control system parameters. In earlier research projects we have developed models of the circulation that take more and more aspects of cardiovascular control into account. This has broadened the scope from the baroreflex and dynamics of sympathetic and parasympathetic control of the circulation ((4),(5)) to the effects of gravity and the cardiopulmonary reflexes ((7)) and, finally, to a model that takes instantaneous lung volume (ILV) and central venous pressure changes into account ((1), (15)). Furthermore, we have the analysis tools to extract instantaneous system parameters: transfer from blood pressure to heart rate, from ILV to blood pressure etc. The recently developed technique of multivariate autoregressive parameter estimation ((9),(6)) has, in essence, enabled the on-line computation of essential control parameters even in rapidly changing systems. This is an important requirement to be able to keep close track of the development of, for instance, a vasovagal syncope or other alarm conditions. In the AORTA-project we intend to bring these techniques to the clinical arena by making the analysis results immediately available to the attending clinician, as part of the bedside monitor information.The astronauts will be invited to the PI's lab for the baseline protocol only. Here they will undergo a dynamic tilt table protocol under two different conditions: once 'as they are', once with thigh-cuffs (like blood pressure cuffs, adapted to the form and size of the thigh) inflated to a pressure of 40 mmHg in the supine position, to 100 mmHg while upright. This induces acute volume depletion, and we compare the cardiovascular control capacity in the two conditions. The total protocol in PI's lab will take 3 hours. Later repetitions of a simplified protocol: tilt and breathing, no cuffs, no dynamic tilt table, will take around half an hour and can be combined with one of the other BDC protocols.

Hypothesis: The hypothesis to be tested is that it is possible to predict postflight orthostatic intolerance by computation of the parameter set for cardiovascular control quality as it is established in the AORTA-protocol (Amsterdam On-line Real Time Analysis), that the astronauts undergo preflight at the Academic Medical Center.

Significance: Orthostatic intolerance is one of the readaptation problems that astronauts have to overcome when returning to Earth (or to any surrounding that has g for that matter). Being able to predict who has to take the most vigorous (pharmacologic) measures to prevent situations where the physical inability to act correctly at the right moment (bailout on immediate danger for instance) may prove to be life saving operational information. Application of this knowledge can supersede the indiscriminate intake of salt and water that is used at present, that even might turn into a disadvantage when applied at the wrong moment or in the wrong circumstances.

Methods: The methods to be used are non-invasive measurement of cardiovascular parameters: ECG, finger blood pressure, thoracic impedance and transcranial Doppler blood flow velocity during test protocols aimed at systematically challenging the cardiovascular system. Two types of protocols will be used: one elaborate, where the test subject is placed on a computer controlled fast tilt table and subjected to various frequencies of tilt movements and one simple, where the subject is asked to perform a (non-straining) paced breathing protocol in the supine and upright position. The test subject will be placed on a specially designed tilt table. This instrument has been designed in the Ph.D. project of. E.M. Akkerman. The design purpose was to make a programmable tilt table that could move from 0 to +70 degrees head up in 1 second without inducing vestibular problems or 'launching-effects'. This was eventually obtained by the design shown in fig. 1: a tilt table that moves the head along a vertical line and the hips along a horizontal line (sliding point). The accelerations are such that the body, and in particular the head, is at all times supported by the table and has no tendency to be 'lifted off' the table during the deceleration phase of the motion. The table weighs 350 kgs and is computer driven .

Ground based studies: The astronauts will be invited to the PI's lab for one extensive baseline protocol. Here, they will undergo a dynamic tilt table protocol under two different conditions: once 'as they are', once with thigh-cuffs (like blood pressure cuffs, adapted to the form and size of the thigh) inflated to a pressure of 40 mmHg in the supine position, to 100 mmHg while upright. This induces acute volume depletion, and we compare the cardiovascular control capacity in the two conditions. The total protocol in PI's lab will take 3 hours. Later repetitions of a simplified protocol: tilt and breathing, no cuffs, no dynamic tilt table, will take around half an hour and can be combined with one of the other BDC protocols (Circa-protocol for instance).

New information expected: The outcome of this experiment is the rejection or confirmation of our prediction on orthostatic (in?)tolerance directly after spaceflight. A good predictor test will help identify those candidate astronauts who need special measures on return to earth, like salt- and water conserving drugs in combination with (salt and) fluid loading. Moreover, in every-day medicine it will help to better identify patients with hidden orthostatic problems that sporadically come to expression under unfavorable circumstances.

Research instruments used in this experiment

Fig. 1: Sketches of the tilt table in different positions, from left to right and from top to bottom at -30, 0, +35 and +70 degrees. A small circle indicates the sliding point.

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