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Arthero-Space project: A model based exploration of the regulatory mechanism of the microcirculation for the prevention of orthostatic intolerance

Final Report Summary - ARTHEROSPACE (Arthero-Space project: A model based exploration of the regulatory mechanism of the microcirculation for the prevention of orthostatic intolerance)

The cardiovascular system relies on a complex synergy of control mechanisms to maintain blood pressure and cerebral perfusion, but the system malfunctions during astronauts’ re-entry from space. Better understanding these regulatory mechanisms will improve countermeasures. The main objective of Artherospace project is to assess the regulatory mechanisms of the cardiovascular system in response to changes in hydrostatic pressure by combining in vivo experiments and numerical blood pressure wave propagation model.

Research activities:
An in vivo study have been performed that focuses on the muscle pump effect which is an influential phenomenon in orthostatic tolerance via increased venous return. The experimental protocol including both tilt-table and Lower Body Negative Pressure orthostatic stresses was applied to a group of 12 healthy volunteers. This study demonstrates that muscle contraction induces large blood pressure reactions and dramatically increases the perfusion of the lower limb with a characteristic time scale in the order of 10 seconds that correspond to cardio-postural interaction. Furthermore, it is shown that orthostatic stress does not significantly influence the haemodynamics response. With this study, we obtained quantitave estimates of the muscle pump dynamics that will contribute to further investigation its the role in orthostatic tolerance and tissue perfusion. The results of this study have been presented to international conferences and a scientific article is under review.

A second in vivo study has been performed to characterize changes in cardiovascular parameter, as cardiac output, based on balistography techniques. This method, initially used for space flight, allows the non-invasive assessment of relative changes in cardiac output derived from acceleration signal recorded with a high resolution weight scale. Within this study, a comprehensive characterization of balistography signals have been obtained for 20 subjects under different physiological conditions. The goal of this study was to determine the relationships between cardiovascular parameters, e.g. cardiac output and stroke volume, and the ballistocardiogram. It is found that the acceleration of the blood in the aorta is expected to influence the balistogram more than the the stroke volume. Combined with computational model study, this work will contribute to the clinical implementation of balistography techniques in clinics. This research is part of a larger project which obtained financial support from the French Canadian Research Fund and is performed in collaboration with the group of Prof. Gerbeau from the French research institute INRIA and Dr. Kouhyar Tavakolian from University of North Dakota (USA). The result of this study has been presented at the 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society and result in a peer review proceeding. We are expected to publish the results of this study in a peer review journal.

In addition, the MC fellow broadened the scope of Artherospace project with the study of orthostatic intolerance with micro-gravity experiments on parabolic flight. A pilot study has been performed in co-operation with Dr. Limper (Wuppertal Uni. Hospital and DLR, Germany). Vascular ultrasound feasibility has been tested with success and the results have been published to the international peer-review journal Microgravity science and technology.

A last in vivo study is currently running on a Short Arm Human Centrifuge. For long-term space missions, astronauts follow a specific training program to maintain their physical shape. Physiological responses to artificial gravity need to be better understood. The objective of this study is to estimate the reproducibility and accuracy of remotely controlled vascular ultrasound assessment under centrifugation conditions by assessing peripheral vascular responses. Preliminary results suggest that common carotid artery blood volume flow is maintained during centrifugation whereas diameter slightly decreases. The femoral artery blood flow significantly decreases with no significantly different diameter. The results of this study will be essential to better design countermeasure program for astronauts and better understand blood pressure regulations mechanisms under gravitational stress.

To go beyond assessed parameters in vivo and better understand the role of gravity on blood pressure regulation computational model is used. The development of a one dimensional model is implemented by Joke Keijsers, PhD student whose main supervisor is the MC fellow. Venous bio-mechanical behavior has been implemented using collapsible tube law, venous valves have been modeled and effect of gravity (hydrostatic pressure) has been added. We have demonstrated the importance of proximal venous valves and the superficial venous system for the muscle pump effectiveness. Currently, the model is further developed to include vascular regulation that will allow a better fit between in vivo and numerical data. A scientific paper has been presented at international symposium and the results have been published to the peer-reviewed International Journal for Numerical Methods in Biomedical Engineering.

Training activities:
The fellow extended her skills during the 3 years of this project on several levels. She has gained experience in writing ethical proposals for an in vivo study, writing scientific articles as well as presenting at international conferences. She has acquired new skills in writing research grants as project coordinator for a bed-rest study proposed by the European Space Agency (proposal which has been accepted), and a EU Horizon 2020 proposal (first phase submitted). She has gained experience in leadership and has co-supervised PhD and bachelor students, and gained experience in teaching by being involved in a graduate course on space physiology at SFU. Furthermore, she has organized and led an international seminar that was attended by more than 50 international guests at the DLR. She also gave several invited seminar talks at renowned universities and research institutes: University of Toronto, Canada, Technical University of Munich and Constance University in Germany, Brunel University in England, and INRIA in France. Finally, she has developed further her personal skills and followed German courses as well as a workshop dedicated to leadership skills.

Transfer of knowledge activities:
Cooperation between the host institution (space physiology institute, DLR) and the research laboratory at SFU in Canada has been established in a sustainable manner. A PhD student supervised by the MC fellow has spent 3 months at the aerospace laboratory at SFU as a research-guest. Furthermore, joined research projects are forecast (for instance on parabolic flight campaign). Dr. Blaber (SFU) and the Dr. Leguy will be co-investigator in a large physiological study that will be organized by ESA in 2016. The fellow has been very active in promoting her research and gravity sciences in general. She is actively supporting the scientific community by being committed since 2011 as a committee member of the European Low Gravity Research Association (ELGRA). Within this framework, she has created a social network (Facebook) that counted more than 100 members with interest in gravity related research and has initiated a student group that currently gather more than 50 students from all over Europe. She has also worked as coordinator for the conference student sponsorship and competition of ELGRA general assembly. Finally, she has recently joined the Marie Curie Alumni Association and plays an active role in the German chapter working with other alumni members on the organization of Café Scientific events that will be open to the general public.

A website dedicated to Arthero-Space project, where the research outputs as well as outreach activities are promoted, has been created and is accessible under the following address: