BME Seminar

Speaker: Dr. Chris Ellis Ph.D.

Title: Microvasculature Regulation of Oxygen Supply: the most important control system on planet Earth?

Time: 4:00-5:00 PM

Date: Thursday, May 29, 2014

Location: E2-330 Engineering Building, Fort Gary Campus

Some refreshment will be provided for after the seminar.

To see the list of next scheduled BME seminars, please seehere:

http://umanitoba.ca/biomedical_engineering/courses/bme_seminars.html

Abstract of the talk

Oxygen plays a critical role in almost every cell of the body, from energy production in the mitochondria to generation of key signaling molecules such as nitric oxide and carbon monoxide. To fulfill these functions, O2 must diffuse from an O2 source (e.g. erythrocyte in a capillary) through the cell (or cells) to the site where it will be used (consumed). But diffusion into an O2 consuming tissue places a biophysical limitation on the maximum cell size and the maximum distance between O2 sources within an organ. Ninety five years ago Krogh was the first to recognize that it was not adequate to simply deliver the correct amount of O2 to an organ, the vasculature needed to match the distribute the O2 supply to the O2 needs of the tissue to within a few 10's of micrometers of where it would be consumed. To meet this design constraint Krogh proposed that capillary density was actively controlled; as O2 consumption increased more capillaries would be recruited to minimize diffusion distances. Despite the importance of Krogh's insights, there was a fundamental flaw in his model of tissue oxygenation and his concept of capillary recruitment has never been proven. This talk will describe our current understanding of how the microvasculature regulates the distribution of O2 supply within a tissue. The situation is far more complex than controlling capillary density due to a wide range of factors such as the unique fluid dynamic properties of blood flow in the network of very small vessels that make up the microvasculature (arterioles, capillaries and venules), the complex three dimensional geometry of the microvasculature and diffusional exchange of O2 among all levels of the microvasculature as well as with the tissue. Our hypothesis is that the O2 supply to individual capillary units (capillaries supplied by a single terminal arteriole) is regulated by the hemoglobin O2 saturation dependent release of ATP (adenosine triphosphate) from red blood cells in capillaries and that receptors on the capillary endothelium detect the ATP levels and signal upstream arterioles to dilate via conducted hyperpolarization of endothelial membrane potential. To test the hypothesis that individual capillary units can regulate their O2 supply, we used a microfluidic device to perturb O2 levels in small groups of capillaries at the surface of skeletal muscle in rat hindlimb and a dual wavelength intravital video microscopy system for measuring red blood cell flow and O2 saturation in these capillaries. BME PhD student, Nour Ghonaim, demonstrated that individual capillary units were able to signal for an increase in O2 supply when capillaries were exposed to low O2 levels. Since O2 levels in arterioles were not affected this result supports our hypothesis of a conducted signal from capillaries to arterioles. Our conclusion is that discrete networks of capillaries, with the red blood cell as the O2 sensor, are able to regulate upstream arteriolar resistance to ensure that the distribution of O2 supply matches the O2 needs of the tissue and that O2 regulation occurs at the level of capillary units not individual capillaries as proposed by Krogh.

Bio of the Speaker

Dr. Christopher Ellis graduated from McMaster University in Hamilton with a B.Eng. degree in Chemical Engineering. In 1980 he completed his Ph.D. in Chemical Engineering at Northwestern University in Evanston, Illinois. He began his postdoctoral training with Alan C. Groom in Biophysics at The University of Western Ontario in 1979 and in 1982 he was appointed as an Assistant Professor supported initially by a Senior Scholarship (1982-89) and later a Career Investigator Award of the Heart and Stroke Foundation of Ontario (1989-94). From 1995 through 2004 he served as Graduate Chair for Medical Biophysics. From June 2006 to June 2009 he served as Assistant Dean - Research, Schulich School of Medicine & Dentistry and from July 2009 to December 2009 as Associate Dean - Research. He is currently a Professor in the Departments of Medical Biophysics and Medicine.

Dr. Ellis has trained over 20 graduate students, clinical trainees and post-doctoral fellows. He has published over 80 journal articles with total of ~3200 citations. His research on oxygen transport in the microvasculature has been funded by grants from CIHR, Heart and Stroke Foundation of Ontario, NSERC and NIH. His research interests include the application of a novel optical imaging system to investigate microvascular oxygen transport in living tissue in animal models of disease, the exploration of the mechanisms responsible for the local regulation of oxygen delivery by the microvasculature in vivo, with particular emphasis on the role of red blood cell as the sensor and regulator of oxygen delivery, and the application of microfluidics to microvascular research.

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Looking forward to your attendance and support for BME.

Zahra

Zahra Moussavi, Ph.D., P.Eng.

Director, Biomedical Engineering Program

Professor & Canada Research Chair in Biomedical Engineering; http://umanitoba.ca/biomedical_engineering/ http://umanitoba.ca/biomedical_engineering/

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