Select Committee on Science and Technology Written Evidence

Memorandum 9

Submission from the Osmosis Unit


  1.1  Ongoing UK space medicine research, performed by the Osmosis Unit, has identified a mechanism of fluid balance shifts in astronauts. Confirmation of this mechanism is predicted to lead to the development of novel pharmacological agents to overcome these fluid shifts, make space flight more tolerable, and prevent the orthostatic intolerance presently exhibited by astronauts on their return to Earth gravity. This research will have a positive impact on the status of British Scientists across the world.

  1.2  The terrestrial impact of this research is predicted to be the development of medical devices for the assisted diagnosis and therapeutic monitoring of hypertension, oedema and shock. In addition, four new pharmacological agents for the treatment of these diseases are apparent from this research.

  1.3  The estimated annual income from the four diagnostic devices and drugs is $4.5 billion. However, for this research and its related intellectual property to remain within the UK, Britain must be an active member of ESA. Failure of the UK to join will inevitably result in the loss of this potential income and its transfer to Europe or the USA.


  2.1  Exposure to just a few days of weightlessness results in the inability to stand on return to the Earth's surface.1-2 Weightlessness also results in a shift of plasma volume from the lower to the upper part of the body3-4 and an overall decrease in total plasma volume.5 These findings challenge the Starling Hypothesis of fluid exchange,6 one of the fundamental hypotheses of cardiology. The implications of this on the diagnosis and therapeutic treatment of cardiac disease are immense.

  2.2  The Osmosis Unit has been investigating fluid exchange since it was spun out of the Health Service in 2000. Fluid balance and exchange are controlled by the interaction of the capillary blood pressure and the osmotic pressure across the capillary membrane (MOP). The MOP of plasma is highly dependent on the pore size (permeability) of the capillary wall7 which is highly dynamic. Pulse Reverse Osmosis8-10 (PRO) is a new theory of fluid exchange which suggests that fluid balance is controlled by capillary pore size and fluid exchange is controlled by the capillary pulse.

  2.3  The changes in fluid balance and exchange in astronauts led to the design of a study investigating the effects of gravity on plasma MOP. Results from this preliminary study are presented below.


  3.1  Change in posture from lying to standing in six informed healthy volunteers resulted in a 13.7% increase (Fig 1) in MOP10K (t test p<0.001), a 10.6% change in MOP1K (p<0.001) and a 0.4% change in plasma osmolality (MOP0K) which was not significant (p = 0.30).

Fig 1 Effect of change in posture on plasma MOP10K

  3.2  The Starling hypothesis predicts that changes in plasma osmotic pressure results from the movement of water between the plasma and the interstitium. If this were the case, the percentage change in MOP's measured across the three membranes should be the same as they would all be diluted by the same amount. However, the measured % change was different for all three measurements (Fig 2).

Fig 2 Percentage change in MOP between lying and standing for MOP 0, 1 and 10k Dalton

  3.3  These changes are consistent with the concept of change of capillary pore size with change in hydrostatic pressure. The finding that the change in MOP10K is greatest suggests that the tight junctions between epithelial cells in the capillary are changing in size with posture.


  4.1  As a follow-on from these preliminary studies we have established links with the department of Sports Medicine at Glasgow University to further investigate these changes. This study has been set up to investigate the osmotic, pulse and blood pressure changes in informed volunteers on a tilt table. Fig 3 is typical of the changes observed.

Fig 3 Cardiac and osmotic changes observed in tilt table tests

  The results from this one volunteer show a slowly increasing MOP10K over the 30 minutes following the change in position, coupled with a transient rise in diastolic blood pressure and pulse rate. The observed changes are consistent with the predictions from PRO that fluid balance is related to pore size and the pulse changes transiently to rebalance fluid exchange.

  4.2  We are planning to incorporate 6° head down tilt into this experiment in order to mimic the effects of hypogravity. If the results of this study are satisfactory we would aim to obtain samples from astronauts in the International Space Station.


  5.1  The short-term aim of the research is to establish the physiological mechanisms underlying the fluid balance shifts and orthostatic intolerance during space flight.

  It is our hypothesis that the body maintains postural fluid balance by constricting the pores in the lower part of the body (below the heart) and opening them in the head. Exposure to long term weightlessness temporarily suppresses pore diameter variation on return to Earth gravity and results in orthostatic intolerance. Identification of the mechanism will enable the development of pharmacological and physical methods of overcoming these changes.


  6.1  In addition to their relevance in space medicine these studies also provide a platform for testing the principles underlying PRO. This hypothesis suggests that hypertension, oedema and shock are all imbalances between the capillary pulse pressure and the plasma membrane osmotic pressure (Fig 4).

Fig 4 Cardiac diseases as predicted by PRO

  6.2  Practical demonstration of the imbalances shown in Fig 4 will logically lead to the invention of novel medical devices for the assisted diagnosis and therapeutic monitoring of these diseases.

  6.3  Fig 4 suggests four imbalances between the capillary blood pressure and the MOP pharmacological treatment would be designed to change the pore size or blood pressure until the patient parameters moved from the disease to the homeostatic area. Four new pharmacological agents would be required to achieve osmotic and blood pressure equilibrium.


  7.1  PRO provides a basis for the design of medical devices for the assisted diagnosis and therapeutic monitoring of hypertension, oedema and shock. Present ECG, blood pressure and other monitoring devices have a market estimated to be $1-5 billion annually. If PRO-related medical devices took 10% of this market, this would represent an income to the UK of $100 to $500 million per year.

  7.2  Profits on a standard me-to cardiovascular drugs are generally in the region of $500 million per year. If less than that most pharmaceutical companies would consider them to be uneconomic. Novel blockbuster therapies are expected to gross at least $1billion annually. PRO suggests four novel pharmacological entities. These have the potential to be worth $4 billion annually to the UK.


  8.1  UK Space medicine research has already suggested a mechanism for fluid shifts in astronauts. Further research should show if the relevance of this mechanism on the development of orthostatic hypotension in astronauts returning to Earth gravity. In addition this research provides a novel method of testing the principles underlying PRO a new physico chemical model of blood pressure. Proof of these principles is predicted to lead to the development of new medical devices and four pharmacological agents. The potential value of these devices and drugs to the UK is estimated at $4.5 billion annually.

  8.2  All of the above is dependent on the UK being an active member of ESA space medicine research program. Failure for the UK to join will inevitably result in the loss of this potential income and its transfer to Europe or the USA.

October 2006


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  2  Fomina G, Kotovskaya A, Arbeille F, Pochuev V, Zhernakov A, Ivanovskaya T. Changes in hemodynamic and post-flight orthostatic tolerance of cosmonauts under application of the preventive device thigh cuffs bracelets in short-term flights J Gravit Physiol 2004; 11(2): P229-30.

  3  Michel EL, Johnston RS, Dietlein LF. Biomedical results of the skylab program Life Science Space Res 1976; 14: 3-18.

  4  Gisolf J, Immink RV, van Lieshout JJ, Stok WJ, Karemaker JM. Orthostatic blood pressure control before and after spaceflight determined by time domain baroreflex method. J Appl Physiol 2005; 98(5); 1682-90.

  5  Johnson PC, Kimsey SL, Driscoll TB Post mission plasma volume and red cell mass changes in the crews of the first two Skylab missions. Acta Astronaut. 1975; 2: 311-7.

  6  Starling EH On the absorption of fluids from the connective tissue spaces. J Physiol. (Lond) 1896; 19: 312-26.

  7  Prior FGR Investigation of the osmotic and hydrostatic pressures involved in pulse reverse osmosis. PhD thesis, University of Wales, 1998.

  8  Prior FGR Pulsing reverse osmosis as the mechanism underlying fluid exchange. Medical hypothesis 1991; 36: 109-13.

  9  Prior FGR, Gourlay T, Taylor KM Pulse Reverse Osmosis: a new theory in the maintenance of fluid balance. Perfusion 1995; 10: 159-170.

  10  Prior FGR, Gourlay T, Taylor K, Bryson P, Hope S and Stroev P, Filtration, Pulse and Permeability, An update on Pulse Reverse Osmosis. Filtration 2005; 1: 113-128.

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