Cardiovascular Physiology: Microcirculation and Capillary Exchange

Proceedings of the 28th International Congress of Physiological Sciences, Budapest, 1980

A. G. B. Kovàch, J. Hamar, L. Szabó

• Publisher: Pergamon
• Year: 2013
• Print ISBN:
  9780080268194
• eBook ISBN:
  9781483189956
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

Advances in Physiological Sciences, Volume 7: Cardiovascular Physiology: Microcirculation and Capillary Exchange is a collection of papers that tackles the advances in the understanding of microcirculation and capillary exchange. The text first details the coordination of microcirculatory function with oxygen demand in skeletal muscle, and then proceeds to discussing the role of intravascular pressure in the regulation of the microcirculation. Next, the selection covers the circulatory actions of prostacyclin and thromboxane, along with the routes of transcapillary transport. The last two parts of the text deal with the lymphatic system and blood-brain barrier. The book will be of great interest to health professionals, particularly cardiologists and cardiovascular surgeons.

COORDINATION OF MICROCIRCULATORY FUNCTION WITH OXYGEN DEMAND IN SKELETAL MUSCLE

Brian R. Duling, Department of Physiology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA

Publisher Summary

This chapter presents some facts showing how microcirculatory parameters other than bulk flow of blood to the tissues may be controlled. It discusses the way in which various microvessel elements may interact with one another. The chapter focuses on the ways in which oxygen delivery to cells is regulated. It further discusses four variables: (1) arteriolar diameter (flow control), (2) capillary density (diffusion distance), (3) O₂ content (hematocrit), and (4) cell PO₂. It also discusses how they are interrelated by microvascular control systems to regulate cellular oxygen delivery. Within this context, the chapter discusses the way in which the microvascular elements vary and interact during regulation of blood flow and whether the available evidence is consistent with the idea that the system is designed to regulate tissue PO₂ within narrow limits. A large part of the work done to date on the local regulation of circulatory function has been carried out on perfused organs of various sorts, and microvessel behavior is inferred from measurements of flow and the capillary filtration coefficient or permeability surface area product.

Local regulation of the peripheral circulation is most commonly thought of in terms of regulation of blood flow, and processes such as autoregulation, functional hyperemia, and reactive hyperemia are all taken as indices of the coupling between peripheral circulatory function and tissue metabolism. When other variables such as hormonal influences and neuronal control mechanisms are excluded, a tight parallelism is usually found between flow and the metabolic needs of tissues. This relation has in the past led to the virtual exclusion of other elements of microvascular function from consideration in local regulatory processes. In this discussion I will examine some of the facts showing how microcirculatory parameters other than bulk flow of blood to the tissues may be controlled and, in addition, how various microvessel elements may interact with one another.

The focus of the discussion will be on the ways in which oxygen delivery to cells is regulated. This is not intended to indicate that oxygen is the sole substance of interest in regulation of the peripheral circulation, but rather, is simply the focus for a line of investigation which we have been following for several years. For analytical purposes the problem of relating cellular oxygen delivery to microcirculatory function can be broken down into a schema such as that shown in Figure 1.

Figure 1 Determinants of Cellular O₂ Delivery.

The left side of the figure shows the variables which must be known in order to specify the diffusive flux of oxygen from a capillary to a cell. Assuming a constant diffusion coefficient for oxygen, simple diffusion theory can predict O₂ delivery from a knowledge of diffusion distance (capillary density), and the difference between the PO₂ of the cell and the capillary. The right side of the figure shows a number of variables which may determine the capillary PO₂. Capillary PO₂ would, of course, also be influenced by the state of arterial oxygenation and by phenomena such as diffusional shunting above the level of the capillary bed. However, the essence of the findings to be presented here is that the variables shown in the left side of the figure can be measured directly using appropriate microvascular methodology, and thus one need not know what factors contributed to the capillary PO₂, only that the capillary PO₂ in the vicinity of the metabolizing cells had a certain value. For the purposes of the present discussion, it is also assumed that the tissue is in the steady state and that O₂ diffusion to the cells is equal to the consumption rate.

I will focus on four variables and how they are inter–related by microvascular control systems to regulate cellular oxygen delivery. These are: arteriolar diameter (flow control), capillary density (diffusion distance), O₂ content (hematocrit), and cell PO₂. Within this context, two broad issues will be addressed. First, how do the microvascular elements (diameter, density, and hematocrit) vary and interact during regulation of blood flow? Second, is available evidence generally consistent with the idea that the system is designed to regulate tissue PO₂ within relatively narrow limits? An additional point which will be emphasized is that it may not be a simple matter to recognize a regulated process in a system as complex as this one.

A large part of the work done to date on the local regulation of circulatory function has been carried out on perfused organs of various sorts and microvessel behavior is inferred from measurements of flow and the capillary filtration coefficient or permeability surface area product. Behavior of the tissue oxygen consuming processes has been inferred from analysis of mixed venous blood. All of these measurements provide indirect estimates of the variables shown in Figure 1. Additional factors such as: variable behavior of series elements in the microvasculature, regional heterogeneities within the tissues, and possible shunting of gases between arterioles and venules, present difficulties in making clear statements of conditions at the level of individual cells (Duling & Klitzman, 1980).

We have approached this research by utilizing relatively recent improvements in techniques for studying the microcirculation (Johnson, 1972) to examine the relations among microcirculatory parameters and striated muscle contraction. The basic experimental paradigm has been to attempt to focus measurements on small, reasonably well defined units, consisting of arterioles, capillaries, and associated striated muscles, and to examine how these elements interact. The net result of oxygen consumption by tissue and microcirculatory oxygen supply has been assessed using the oxygen microelectrode developed by Whalen et al. (1967). With this electrode we can measure PO₂ at locations confined to a few microns in diameter and, when combined with appropriate microscopy, the exact position of the electrode relative to microvascular elements and striated muscle cells can be ascertained.

Typically, we have chosen the minimum tissue PO₂ as a parameter to be measured; this is obtained by visually selecting a site for study which is at the venous end of a capillary and midway between a pair of capillaries, thus approximating Thews’ “lethal corner” (Thews, 1960). This point was chosen as it may have important implications in regulation of flow and metabolites since it will be the first part of the tissue whose function is limited by O₂ availability (Honig et al., 1971).

DIAMETER CHANGES DURING MUSCLE CONTRACTION

The relations between oxygen supply and demand have been varied experimentally in two ways, either by changing the tissue metabolic rate by stimulation of the striated muscle cell, or by changing the apparent O₂ consumption by varying the PO₂ of a superfusion solution covering the tissue. An increase in superfusion solution PO₂ is used to mimic a decrease in oxygen consumption by the tissue, since a fraction of the oxygen can be supplied from the solution and need not be supplied by vascular means.

Figure 2 shows how arteriolar diameter is influenced by changes in superfusion solution PO₂. Elevation of the superfusion solution PO₂ results in an increased tissue PO₂ (Fig. 6A) and a corresponding decrease in arteriolar diameter. The decrease in arteriolar diameter reduces flow and minimizes the change in PO₂ which is induced by superfusion with a solution containing high oxygen (Duling, 1972; Gorczynski & Duling, 1978).

Figure 2 Effect of Changes in Superfusion Solution PO₂ on Arteriolar Diameter in Resting and Contracting Striated Muscle.

Stimulation of the striated muscle can be combined with alterations in superfusion solution PO₂ to permit independent variation of tissue PO₂ and muscle work (Fig. 2). In the experiment depicted here, superfusion solution PO₂ was varied either during resting conditions or during stimulation of the striated muscle at 1 Hz. Stimulation of the striated muscle resulted in a vasodilation and a fall in tissue PO₂. However, even during contraction, the striated muscle microcirculation continued to constrict in response to elevations in superfusion solution PO₂.

The difference in arteriolar diameter at rest and during contraction reflects the microvessel equivalent of functional hyperemia, and this functional dilation varies with both the initial state of the microcirculation and with the initial tissue oxygen tension. As superfusion solution and tissue oxygen tension are elevated, functional dilation is diminished. Using the relation between vascular conductance and the fourth power of the diameter, we have estimated that the findings are consistent with a progressively smaller conductance change, i.e., functional hyperemia, as superfusion solution PO₂ is elevated (Damon, unpublished).

Both tissue PO₂ and diameter increment are observed to change during muscle stimulation, and we have attempted to establish a cause–and–effect relationship between these two variables (Gorczynski & Duling, 1978). This was done by raising superfusion solution PO₂ during striated muscle contraction so as to return the tissue PO₂ toward the resting value. If variation of tissue PO₂ was the sole controller of arteriolar diameter, then restoration of tissue PO₂ to resting levels during continued contraction should h...

Table of contents

• Cover image
• Title page
• Table of Contents
• Inside Front Cover
• Copyright
• FOREWORD
• Chapter 1: COORDINATION OF MICROCIRCULATORY FUNCTION WITH OXYGEN DEMAND IN SKELETAL MUSCLE
• Chapter 2: THE ROLE OF INTRAVASCULAR PRESSURE IN REGULATION OF THE MICROCIRCULATION
• Circulatory actions of prostacyclin and thromboxane
• Routes of transcapillary transport: Correlation of structure and function
• The lymphatic system: Functioning and interrelationships
• Blood-brain barrier
• INDEX