The microcirculation is essential to many functions of the organism.

Its central role in the function of the cardiovascular system was emphasized by Carl J. Wiggers, the deanof cardiac physiologists of the past century, who wrote: inour zeal to interpret the importance of the heart and great vessels it should never be forgotten that the more obvious phenomena of the circulation are but a means throughwhich the real object of maintaining an adequate capillary flow is attained.

I.1.1 Functions of the microcirculation In addition to delivering nutrients and removing waste products essential for moment to moment function, the microcirculation plays an essential role in fluid exchange between blood and tissue, delivery of hormones from endocrine glands to target organs, bulk delivery between organs for storage or synthesis and providing a line of defense against pathogens. To execute these functions satisfactorily, certain features are necessary in the microcirculation. In the description that follows we provide an overview of these features, based in large part on skeletal muscle, which constitutes 50% of body mass and has perhaps the largest capability of any organ for altering blood flow according to need. On a practical level, it is also more accessible for microcirculatory studies than most other organs. Certain specialized features of the microcirculation of other organs are also described. I.1.2 Denition of the microcirculation As a first approximation, the microcirculation consists of those blood vessels too small to be seen with the nakedeye. This limitation of visual acuity required Harvey in1628 to postulate the existence of invisible pores of the flesh to support his hypothesis that blood passes through microscopic channels in circulating from artery to vein. However, Harveys critics suggested that such porositiesdid not exist but rather that blood moved through the tissue by a general seepage. Development of the first single lens microscope enabled Malpighi in 1661 to observediscrete capillaries connecting arteries and veins in the tortoise lung. Van Leeuwenhoek in 1674. Was able to provide quantitative information on the size and spatial density of microcirculatory vessels in the tail fin of the eel as well as measure the velocity of red cells in these vessels. Both investigators provided critical support for Harveyshypothesis. With further development of the microscope, the histology of the vascular wall and the existence of acontinuous layer of endothelium lining the vessels weredescribed. Subsequent studies led to an appreciation of the specialized structure and topological organization of the smaller vessels located within organs and the manner in which they differ from the larger conduit vessels that distribute blood flow to the organs.The

rheological properties of blood in the microcir-culation differ from those in the large vessels due to theFahraeus and Fahraeus-Lindqvist effects, which lead todiameter-dependent reduction of hematocrit and effec-tive blood viscosity in these vessels. This feature becomesincreasingly important in vessels less than 100m luminaldiameter.There is also significant phase separation of red cells and plasma at bifurcations in the

microcirculatorynetwork as described by August Krogh. These phenom-ena are considered in Section I, Chapter 1 of this volume.Microcirculatory studies most commonly involvedirect observation under the microscope as in the examplesgiven above. However, studies of the exchange process inthe microcirculation between blood and tissue have alsorelied to a great extent on whole organ studies in which theextraction of diffusible indicators is measured and com-pared under different conditions. Studies of the regulationof blood flow by the microcirculatory vessels have alsobenefited considerably from determination of flow andvascular resistance in individual organs and in the wholeorganism.

I.2 MICROCIRCULATORY ORGANIZATION AND STRUCTURE The microcirculation is organized into three principal sections, arterioles, capillaries and venules; each has unique structure and function. The arterioles are well invested with vascular smooth muscle and are primarily responsible for delivery of blood to localized tissue areas and regulation of the rate of delivery. The capillaries possess very thin walls and are primarily responsible for exchange between blood and tissue. The venules drain blood from the capillaries for return to the heart and generally parallel the arterioles in organization. They are important for macromolecular exchange, postcapillary vascular resistance and immunological defense. I.2.1 Arterioles I.2.1.1 Network organization As we follow the distribution of blood from the heart and aorta through the major arteries to the successively smaller and more numerous branches of the arterial system, a region of the network is reached whose structure is recognizably different from the larger, upstream vessels. Spalteholz, and later Krogh described the microcirculation as beginning with an anastomosing network of vessels, the large arterioles, followed by a tree-type network of smaller arterioles, an anastomosing network of capillaries and a network of venules that is organized in a manner similar tothat of the arterioles. The various levels of the arteriolar network differ inrespect to function as well as structure. To aid in analy-sis, several schemes have been used to classify vessels.The simplest classification is by internal diameter.

Thisclassification enables a particular function of the arteri-oles to be quantified and compared as a function of rest-ing diameter. A limitation of this approach is that vesselsat the same level in the vascular network, presumablyhaving very similar functions and environment, may havesignificantly different resting diameters. To overcome thislimitation, Wiedeman designated the large arterioles aris-ing from small arteries as first order vessels and succes-sive, smaller branches as 2nd order, 3rd order etc.[9]. Inmost vascular beds five or six orders are identified by thismethod. This system has an element of subjectivity asso-ciated with the assessment of size in designating a branchas a new order rather than extension of the existing order.This method, when applied consistently, does enable com-parison of arterioles at different levels of the network andis useful in comparing findings from different laboratories.Alternatively, the size criterion can be eliminated and gen-eration numbers assigned to each successive segment of thebranching network [10] . This scheme preserves the great-est amount of topological information. A third approach ispresented in the Horton-Strahler

method[11]which beginsat the capillary level and designates the immediate precap-illary vessels as 1st order and the vessel feeding two 1storder vessels as 2nd order. Where a 2nd order vessel meetsanother 2nd order-vessel the feeding vessel is designated3rd order etc. This method is useful in comparing vesselsin the immediate vicinity of the capillary network but losessome of the topological information and is less practical inclassifying vessels farther upstream.Additional complexity is encountered in classifyingvessels in the arcade portion of the network. In skeletalmuscle it has been shown that the loops formed in thisnetwork are characterized by an ellipticity factor which issimilar among loops and an orientation which is generallyparallel to the muscle fibers [12] . I.2.1.2

Structure and dimensions The diameter of vessels seen in vivo depends on the stateof vascular tone and the data presented here were generallyobtained under control conditions. Under these conditionsthe diameter of vessels identified as large arterioles or firstorder vessels by the Wiedeman system varies according to