angiogenesis
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The microcirculation is the business end of the cardiovascular system. It is in this branching network of microvessels that transport and exchange of heat, respiratory gases, nutrients, waste products, water and hormones occurs between blood and the body’s tissues (1,2). Blood flowing in the microvasculature also carries leukocytes and lymphocytes to their tissue targets, and it is here that trafficking of these inflammatory and immune cells takes place between blood and tissue (3,4). Microvessels also importantly contribute to peripheral vascular resistance (5), vascular capacitance (6), and blood pressure regulation (5), and they are the effectors responsible for the control of blood flow to, and within the body’s tissues and organs (1,5,7,). Microvascular smooth muscle cells (1,5,7), or related pericytes (8–12), participate directly or indirectly in all of the listed functions of the microcirculation by controlling vessel diameter and hence local microvascular hemodynamic resistance, pressure, and luminal fluid flow.
Microcirculation is composed of arterioles, capillaries, and venules, where the diameter of blood vessels varies approximately from 5 to 100 μm. The behavior of blood cells, including red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes), is of great interest in physiology and biomedical engineering. Recent advances in numerical methods and computer hardware have allowed us to simulate the behavior of blood cells in microcirculation. In this chapter, we will provide an overview of recent numerical studies on the microcirculation. We first show “2.1 Behavior of capsules in flow” for a fundamental understanding of the modeling of the cell dynamics and then “2.2 Behavior of red blood cells” for a more specific case of red blood cells. We also present numerical analyses of cell adhesion in microcirculation: “2.3 Cell adhesion in microvessels” for the margination and adhesion of leukocytes, tumor cells, and malaria-infected red blood cells and “2.4 Formation and destruction of the primary thrombus” for platelet adhesion and aggregation.
The microcirculation is exquisitely sensitive to, and a vital participant in, an inflammatory response. Two well-characterized responses of the microcirculation to inflammation are an increased blood flow and increased vascular permeability, both of which contribute to the interstitial edema that accompanies an inflammatory response.
The role of specific cellular and chemical mediators of the inflammation-induced increases in blood flow and vascular permeability is addressed along with the molecular basis for these responses. Since chronic inflammation also results in the proliferation of microvessels, which can alter both blood flow and microvascular exchange, the influence of inflammation on angiogenesis is also addressed.
Among direct methods, in vivo microscopy of the microcirculation is available through small cameras mainly restricted to the sublingual area. Earlier devices such as orthogonal polarized spectral and sidestream dark field imaging video microscopes were hampered by technological limitations, but recent-generation handheld microscopes perform better.90–93 These devices make it possible to assess the two determinants of oxygen delivery.