Timothy W. Secomb

Co- Principal Investigator
Physiology
Mathematics

Theoretical studies of the microcirculation

The microcirculation is a network of extremely small blood vessels that supplies oxygen and nutrients to all parts of our tissues. The focus of work in our research group is the use of mathematical and computational approaches to study blood flow and mass transport in the microcirculation. Working in collaboration with experimentalists, we aim to understand quantitatively the processes involved. The main ' areas of our work are:

Mechanics of blood flow in microvessels. We are examining the relationship between red blood cell mechanics and flow resistance in microvessels. Theoretical predictions agree well with observations in glass tubes, but resistance is higher living tissue. Microvascular irregularity and the macromolecular lining (glycocalyx) on the walls of microvessels are possible causes of this increase in resistance. Currently, we are focusing on the role of the glycocalyx. Also, we are studying the relationship between network structure and hemodynamics.

Mass transport to tissue. We are simulating oxygen exchange between networks of microvessels and surrounding tissues in skeletal muscle, brain and tumors. In skeletal muscle, we have shown how oxygen can be exchanged diffusively between arterioles and capillaries, and we are studying the determinants of maximal oxygen consumption. In tumors, we are studying the relationship between network structure and occurrence of local hypoxic(radiation-resistant) regions. In brain, we are examining the gradients in oxygen content around microvessels, and how they are affected by reductions of blood supply, as occurring in stroke. Also, we are analyzing the delivery of chemotherapeutic drugs in tumor tissues.

Growth and adaptation of microvascular networks. We are developing models for the adaptation of network structures to functional demands, in response to mechanical and metabolic signals.

Secomb, T.W., Hsu, R., Ong, E.T., Gross, J.F. and Dewhirst, M.W. Analysis of the effects of oxygen supply and demand on hypoxic fraction in tumors. Acta Oncologica 34, 313-316 (1995).

El-Kareh, A.W. and Secomb, T.W. Theoretical models for drug delivery to solid tumors. Critical Reviews in Bioengineering 25: 503-571 (1997)

Secomb, T.W., Hsu, R. and A.R. Pries. A model for red blood cell motion in glycocalyx-lined capillaries. Am. J. Physiol. 274: H1016-H1022 (1998).