Lehrstuhl für Physiologie

Gravitational Physiology & Medicine: Spaceflight and Aging

Concept

Physiological deconditioning changes induced by spaceflight are similar to those that occur in aging, thus leading to greater incidence of syncope and falls.

The planned research unit - which examines effects of gravitational physiology on physiology and medicine across two groups – has activities in areas of research and teaching. It aims at developing research, national and international networks, capacities as well as promoting student-orientedlearning.

R. RESEACH CONCEPT, PUBLICATIONS, COLLAOBORATIONS

R.1. Forschungseinheit/ Research Unit establishment and maintenance:

Gravitational physiology

Gravitational forces influence human physiology. For example, every time we stand up 450 ml of blood move into the lower limbs within seconds. This could compromise the venous return leading to decreases in stroke volume and consequently cardiac output. Fortunately, the body compensates for the caudal fluid shifts be immediately increasing the heart rate leading to maintenance of cardiac output, global tissue perfusion and mean arterial pressure. Thus a postural change from supine to standing, in a normal healthy person, does not lead to decreases in cerebral blood and the development of syncope (orthostatic intolerance) and falls.

Gravitational effects become more pronounced when astronauts return from the microgravity environment of spaceflight or in the elderly. In both of these cases there is a higher incidence of orthostatic intolerance and syncope leading to falls related events such as fractures or prolonged hospitalization.

Spaceflight and Aging

The microgravity environment of spaceflight causes cardiovascular, neurovestibular as well as muskulo-skeletal changes. The latter include bone loss, muscle atrophy. These physiological deconditioning changes induced by spaceflight are similar to those that occur in aging, thus leading to greater incidence of syncope and falls. Falls, in turn, are associated with high morbidity as they may lead to head injuries and/ or bone fractures. In the elderly fractures of the femur are often associated with long-term immobilization, from which the patients may not be able to recover.

Therefore, spaceflight deconditioning is similar to aging. Furthermore, studies related to spaceflight deconditioning often uses ground-basedanalogues such as immobilization/ bedrest to study the effects of long-term spaceflight. As immobilization is a common feature in the elderly, data from immobilization studies are useful for understanding the processes that occur in the elderly. Postural control deficiencies and orthostatic hypotension are major contributors to falls in the elderly. It would be logical to propose that integrating information from Earth and space provides an avenue for developing new perspectives. For example, scientific insights and methodologies developed in space science research of orthostatic intolerance can be exploited to study cardiovascular, cerebrovascular, and postural sensory motor control systems in male and females.

Research aims and Objectives:

In view of our research interest in spaceflight physiology and aging, and our expertise in cardiovascular physiology, we propose the following:

  1. Investigate Orthostatic intolerance/syncope: Syncope accounts for up to 6% of all EU hospital admissions annually. By the age of 70 half of the population will have experienced syncope at least once. Therefore, understanding the mechanisms of syncope is important, especially with effects to aging and across gender. Mechanisms to be studied include hormones, cardiovascular control, cerebral blood flow and vascular function during syncope.
  2. We will focus on cardio-postural control interactions, which occur during upright posture. During standing, physiological responses (increased heart rate and vasoconstriction) and the effects of skeletal muscle contractions of blood vessels ensure that venous return to the heart and blood flow to the brain is maintained. With increasing age these mechanisms are compromised leading to reduced blood flow to the brain and dizziness, presyncope and fall-related injuries. Detailed analysis of cardio-postural interactions in the elderly would allow for increased understanding of cardiovascular regulation in the aging and suggest ways to prevent syncope.
  3. Mathematical modeling can be applied to quantify complex interactions leading to tools for assessing syncopal tendencies and the design of treatment strategies. Mathematical modeling will be used to analyze complex interactions of mechanisms related to orthostatic intolerance. Modeling allows for quantifying interactions between global and local control mechanisms, allowing: (a) testing of new hypotheses; (b) exploring new diagnostic tools; and (c) developing new experimental protocols. We, along with our collaborators, have experience in developing and testing mathematical approaches.
  4. A physiological model has been recently proposed to rationalize interactions between cardiovascular and postural control in relation to orthostatic stress (Blaber et al., 2009). Recent data indicate a correlation between postural sway and blood pressure. We have observed a relationship between calf muscle EMG activity during passive standing and blood pressure variation. The degree and mode of interaction between cardiovascular control and centrally regulated sensory-motor control has yet to be identified and explored. We will investigate this in the research unit further. The aim is to develop specific tools – using cardio-postural interactions data - that can be used to predict syncope and develop advanced countermeasure strategies.
  5. Physiological instrumentation development. Development of novel, non-invasive instruments that can be used for measurements. This also involves development of new instruments as well as finding new uses for older devices. Also included here is the identification of new biomarkers in blood/ saliva that can be used for stress identification, disease prevention and health monitoring.

R.2. Current publications of the group

Please see Appendix A

R.3.Current ongoing projects

Current projects that are ongoing/ about to start are shown in Appendix B.

List of abbreviations:

ASI: Italian Space Agency

ERAfrica: Collaborative call between Africa and EU

ESA: European Space Agency

FWF: National Research Agency, Austria

FFG: Research Agency, Austria

OeAD: Austrian international exchange fellowship

OeNB: National Bank Project, Austria

R.4. Collaborations

R.4.1. Please see Appendix C for our current international collaborators,

including research organizations and companies.

R.4.2. Local MUG collaborations:

Existing:

  • Collaboration with Prof. Regina Roller-Wirnsberger (Geriatrics)
  • Collaboration with Prof. Andreas Leithner (Orthopedics surgery, MUG) with regards to effects of immobilization on bone and muscle function. Two of my Diplomarbeit students are working with the orthopedic unit.
  • Collaboration with Prof. Franz Fazekas (Neurology) with regards to effects of aging and diseases (Alzheimer’s, Parkinson’s and stroke) on cardiovascular function, cerebral blood flow and vascular function (NationalBank project: under review).
  • Collaboration with Dr Stefan Pilz on the effects of vitamin D on cardiovascular function and blood pressure

Planned/ Discussions ongoing with our local collaborations:

  • Prof Harald Mangge in the area of risk factors and sustainability
  • Prof Brigitte M.Winklhofer-Roob, Institute of molecular biosciences, Uni Graz in the area of nutrition and vascular function
  • Prof Helmut Ahammer, Biophysics, in the area of fractal analysis of retinal vasculature.

F. FUTURE PROJECTS AND COLLABORATIONS

F.1. Planned involvement in projects

F.1.1. EU action group 2 (EIP AG 2: Prevention of falls in the elderly)

We are leading this coalition of partners in the project “SYNCOFALLS” (see

Appendix D). This coalition brings together experts from:

a) Medical Univ. of Graz (MUG), Austria;

b) Karl Franzens Univ., Graz, Austria;

c) Roskilde Univ., Denmark;

d) Frederiksberg Hospital, Denmark;

e) Flemish Institute of Molecular Research (VITO), Belgium;

f) Semmelweis Univ., Hungary;

g) Univ. of Primorska, Slovenia;

h) Univ. of Bari, Italy;

i) Second Univ. of Naples, Italy;

j) Syncope and Falls in the Elderly laboratory, Harvard Univ., USA;

k) North Carolina State Univ., USA;

l) Simon Fraser Univ., Canada.

The primary focus of the coalition is to advance understanding of the fundamental mechanisms involved in responding to gravity-related stresses and how response mechanisms change with aging, a key issue in current global health.

A second focus is to develop treatment strategies for orthostatic intolerance. For example, we are researching a smart-technology-assisted therapy to assist with fluid volume control in the legs of humans with excessive swelling or standing hypotension. This involves smart stockings whose compressive pressure can be varied via external stimuli.

A third focus is to develop quantitative diagnostic tools to assess the potential for syncope and to test new countermeasures. Development will involve linking physiological information on cardiovascular and postural control and mathematical modeling to quantify interactions.

F.1.2. BIOMEDTECH initiative

In collaboration with the three Universities in Graz (Technical University, TU; Medical University of Graz, MUG; and Karl Franzens University, KFU), we are proposing a research topic “ Vessels Analysis”. This BIOMEDTECH initiative examines vessels analysis using novel techniques. Specific vessels that will be examined include retinal vessels.

 

F.1.3. Setting up of a Ludwig-Boltzman Institute (LBI) for Aging There was a recent call for the establishment of a LBI related to aging. We, along with our MUG partners as well as partners from other establishments, are putting up a proposal for the establishment of a LBI for aging at MUG.

Currently, the four pillars of the LBI are:

  • GERIATRICS
  • NEUROLOGY
  • SUGERY
  • PHYSIOLOGY

F.1.4. Aging research and grant applications:

1. With our consortium partners from EIP AG 2, we will submit one or two EU proposals related to the falls prevention initiative under the Horizon 2020 call.

2. Continue with active research in aging with partners from Slovenia (University of Primorksa). We have submitted a joint paper on the effects of immobilization on older subjects who were confined to bedrest for 2 weeks.

Additionally, we are submitting a joint FWF-Slovenia project with our partners in the next few weeks.

F.1.5. Spaceflight research and grant applications:

1. Write proposals towards upcoming bedrest and isolation studies, which are sponsored by European Space Agency (ESA).

F.1.6. Visits to laboratories (Confirmed at present)

  • 1. Prof. Secher, Denmark (one year): To learn techniques for cerebral metabolism measurements + how to construct a Lower body negative pressure device (LBNP) device that is compatible with MRI. It would allow us to assess which areas of the brain get affected at presyncope and how countermeasures such as mental arithmetic modulate these changes in cortical brain activation (submitted a Marie-Curie Intra-European fellowship application + Bank Austria Research fellowship. BA application secured).
  • 2. Prof. Blaber, Canada (two weeks): To learn how to use near infrared spectrophotometry, (NIRS) for calf fluid shifts measurements during postural changes and in different ages (Bank Austria grant secured).
  • 3. Prof. Montani, Switzerland (one month): Measurements of vascular function, using cutaneous laser Doppler. This is a new technique available for measuring reactive hyperemia/ endothelial function, which is noninvasive (invitation obtained).
  • 4. Prof Rittweger, DLR, Cologne (three months): To carry out studies related to the etiology of syncope. The study at DLR is important as it uses equipment and devices that are not available in Graz (invitation obtained).

T. Teaching area

  • T.1. Supervision of students (Diplomarbeit, Masters and PhD level) We are presently supervising 16 Diplomarbeit students, and one PhD student. We want to ensure that these students complete their work and we hope to continue doing this in the future.
  • T.2. Teaching activities (PhD, Freiwahlfachseminars) Presently, Dr Goswami is teaching in the PhD molecular medicine program. We also teach undergraduate students in two weekly seminars for each semester. These will be continued in the future.
  • T.3. Leadership courses and Masters in Medical Education We will attend several courses that are relevant of leadership and gender equality in the future. These will allow us to run the unit smoothly. Presently, Dr Goswami is enrolled in a “Masters in Medical Education” course at the Karolinska Institutet, Stockholm (Course completion: 2015). Dr Goswami will also be taking part in the “Mentoring” course of the MUG in mid-November 2013 and early February 2014.

U. University Courses Establishment

U.1. Establishment of “Masters in Adaptive Physiology and Medicine” course (Postgraduate Diploma Course, one year). We are now designing the content of this course in our research unit as well as searching for potential international lecturers.

 

 

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