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Capillary growth and diffusion distances in muscle
Camp. Biochem. Physiol. Vol. 87A, No. 4, pp. 859-861, 1987
0
Printed in Great Britain
0300-9629/87 $3.00 + 0.00 1987 PergamonJournalsLtd
CAPILLARY GROWTH AND DIFFUSION DISTANCES IN MUSCLE GREGORYK. SNYDER Department of Biology, Box 334, University of Colorado, Boulder, CO 80309, USA (Received 22 October 1986)
Abstract-1. Tissue capillatity in muscle was modelled as square-ordered arrays with capillary-to-fiber ratios (C/F) from 0.5 to ‘infinity’. 2. C/F up to two had marked effects on diffusion distances, but C/F above had only slight effects on average distances and almost no effect on maximal distances. 3. Capillary growth during normal maturation results in C/F around two. Thus, capillary growth in adult muscle may not be an adaptive mechanism for reducing diffusion distances.
INTRODUCI’ION
Capillary growth is generally considered an effective mechanism for reducing diffusion distances to compensate changes in tissue oxygen demands or tissue oxygen supply (Krogh, 1919; Kety, 1957; Turek er al., 1972; Tenney, 1974; Banchero, 1982; Hudlicka, 1984). However, recent studies show that capillaries may not be produced in muscle following exercise or hypoxia (Cassin et al., 1971; Sillau and Banchero, 1977; Appell, 1978; Sillau et al., 1980; Pietschmann and Bartels, 1985; Snyder et al., 1985). Therefore, the relationships between capillary growth and tissue oxygenation may be more complicated than previously throught. The purpose of this report is to provide a quan-
titative estimate of the relationships between capillary growth and diffusion distances in muscle. The results show that there is a limit to the benefit of increasing capillarity, reached at capillary-to-muscle fiber ratios (C/F) around two. Additional capillaries beyond two per fiber do not decrease diffusion distances into the cell interior. MATERIALS
AND METHODS
Kayar er al. (1982) developed a series of models to describe the relationships of capillarity and diffusion distances in normal adult muscle. These models are extended to include the effects of capillary growth on diffusion distances. Capillaries were arranged as. points in squareordered arrays with the capillary-to-fiber ratios (C/F) preset at values ranging from 0.5 to ‘infinity’; in the latter case, when the entire perimeter of each fiber was filled with capillaries. I selected the square-ordered array because a number of studies have shown that it accurately reflects tissue capillarity in adult muscle (Schmidt-Nielsen and Pennycuik, 1961; Plyley and Groom, 1975; Kayar and Banchero, 1983). In addition, similar results are obtained using other models. Initially, fibers of different sizes were used. However, fiber size did not a&t the outcome of the results. Therefore, the final models were based on fibers assigned an arbitrary dimension of 1 unit squared. Since the capillaries were drawn as points, the dimensions of the capillaries themselves did not contribute to diffusion distances. However, the positions of the capillaries contributed to the distances measured. Therefore, the results are
based on capillary positions that minimized distances into individual fibers. Finally, capillarity is equated to C/F since other measures such as capillary density (CD) and the numbers of capillaries around each fiber (CAF) were not consistent indicators of capillarity; e.g. when C/F is one, CAF may be 2 or 4. Distances were measured from 100 points set within each fiber to the capillary closest to each point (Thews, 1962; Martini and Honig, 1969). The points assigned to each fiber were set at fixed intervals along grid lines oriented randomly to the capillaries (Weibel, 1969). This ‘systematic’ approach to sampling the distances is generally accepted as preferable to a “nonrepresentative sampling from a failed attempt at random sampling” (Greig-Smith, 1957; Kayar er al., 1982). Diffusion distances are expressed as the cumulative frequency distribution of the measured distances. This ap preach provides a simple means of calculating the probability that any given area of tissue within individual muscle fibers will be within a given distance of a capillary. RESULTS
When C/F is increased from 0.5 to 2.0, average diffusion distance decreased by 55% and maximal diffusion distance (FQ, in Fig. 1) decreased by 64%. However, when C/F was increased from 2.0 to ‘infinity’ the average distance decreased by 50% and the maximal distance by 19%. Thus, the benefit of completely surrounding each fiber with capillaries on the average distance is less than when C/F was increased from 0.5 to 2.0 and for the maximal distance, there is essentially no benefit at all. It is also notable that at lower C/F adding capillaries has the greatest effect on longer distances whereas at higher C/F adding capillaries reduces the shorter, but not the longer, distances (Fig. 1). DISCUSSION
Normal growth in muscle, which occurs by hypertrophy of existing fibers rather than addition of new fibers to the muscle bed (Goldspink, 1972; Sillau and Banchero, 1977; Rip011 et al., 1979), has two important consequences for an understanding of the benefits of capillary growth. First, increased fiber cross sectional area (FCSA) associated with growth 859
GREGORY
Distance
Fig. 1. Cumulative frequency distribution of distances from 100 points distributed uniformly through a muscle fiber to the capillary nearest to each point when the capillary-tofiber ratio is increased from OS to ‘infinity’; in the latter case, when the perimeter of the fiber is filled with capillaries. Note the arrow indicating the 95% frequency which, for convenience, is taken as the maximal diffusion distance into the muscle fiber. Note also that distance refers to the relative length of one side of the fiber; e.g. a distance of 0.5 is SO% of the distance along one side of the fiber or one-half of the square root of the cross sectional area of the fiber. capillaries apart, increasing diffusion distances. Second, preservation of diffusion distances during normal maturation or decreasing diffusion distances to compensate changes in oxygen supply occurs by addition of new capillaries to the perimeters of existing fibers. The results presented here show that adding capillaries, up to two per fiber is an effective mechanism for decreasing diffusion distances. However, adding capillaries beyond two per fiber does not reduce diffusion distances into the centers of fibers; the distance that appears to be the most critical for aerobic metabolism (Henquell et al., 1977). In other words, there may be a ‘design limitation’ to the geometric architecture of microvascular beds in muscle. The effects of this ‘design limitation’ are shown in Fig. 2 where the relationship between FCSA and C/F is plotted for four different muscles (continuous lines) and, from Fig. 1, the expected relationships of FCSA and C/F that will keep 95% of the muscle fibers within the same distance; e.g. keep maximal diffusion distances constant (dashed lines). For aerobic skeletal muscle in dogs and cardiac muscle in rodents, increased FCSA appears to be coupled to increased C/F to keep diffusion distances constant. However, for skeletal muscle in rodents, increased FCSA is greater than can be satisfied by increased C/F and diffusion distances increase with age. The data as presented in Fig. 2 illustrate a number of key features of the relationships between capillary growth and diffusion distances in muscle. For example, the shorter diffusion distances in the more highly pushes
K.
SNYDER
aerobic muscle, the heart, are due to the inclusion of more fibers with smaller FCSA rather than increasing C/F (Fig. 1). This pattern is consistent with capillarity in mammalian muscle generally where there are marked differences in CD and diffusion distances, but only limited differences in C/F (Schmidt-Nielsen and Pennycuik, 1961; Plyley and Groom, 1975; Hudlicka, 1984); the highest reported CD is for shrew, Suncus etruscus, papillary muscle, CD = 7287 caps/mm’ and the lowest is for rabbit gastrocnemius, CD = 341 caps/mm2 (Plyley and Groom, 1975; Pietschmann et al., 1982). The C/F for these two muscles, 1.7 caps/fiber, are identical. The differences in CD are due entirely to FCSA, 240,um2 for the shrew and 4785 pm2 for the rabbit. It is also apparent that the extent to which muscles can increase in size via hypertrophy and keep diffusion distances constant is limited and more apparent in the muscles with smaller ‘initial FCSA. Thus, from an FCSA associated with C/F = 0.5, fibers can increase about eight-fold in cross sectional area when C/F is increased to 2.0 (Fig. 2). Finally, C/F in adult muscles approach values that provide a maximal benefit to diffusion distances; capillary growth during normal maturation may result in C/F that represent the upper limit for reducing diffusion distances. Therefore, hypoxia, etc. may not result in capillary growth in adult muscle because there is no gas transport benefit to be derived from the additional capillaries. This scenario of a limited benefit to capillary growth is consistent with results from a wide variety of studies and may explain why: (1) cardiac hypertrophy in adult animals is not attended by the development of new capillaries (Henquell et al., 1977; Turek and Rakusan, 1981); (2) hypoxia DOG
5.0': 0 x NE 4or 9 CI
?! a
3.01
I-_
0
Capillaries
per Fiber
Fig. 2. Relationship of fiber cross sectional area (FCSA) and number of capillaries per fiber (C/F) in four muscles (continuous lines) and, from Fig. 1, the relation of FCSA and C/F necessary to keep the maximal diffusion distances (R& in the muscle constant. The bs is 23.2 pm for dog, 17.4 pm for guinea pig skeletal muscle, and 11.3 pm for guinea pig cardiac muscle. Data from Aquin er al., 1980; Aquin and Banchero, 1981; Kayar and Banchero, 1984.
Capillarity and diffusion distances
results in the development of new capillaries in the myocardium of young rats, but the differences between experimentals and controls disappear as myofibers grow past normal adult values (Kayar and Banchero, 1985); (3) severe hypoxia per se may not stimulate capillary growth in skeletal muscle (Cassin et al., 1971; Turek et al., 1972; Sillau and Banchero, 1977; Appell, 1978; Snyder et al., 1985) and (4) capillary growth in adult skeletal muscle is limited to muscles containing primarily fibers low on oxidative capacity with low initial C/F and the resulting C/F may approach, but do not exceed, C/F in oxidative fibers of control animals (Cotter et al., 1973; Brown et al., 1976; Jackson ef al., 1985; Snyder, et al., 1984; Snyder, 1987). In conclusion, there is limited potential for decreasing diffusion distances in muscle because capillaries are added to the perimeters of existing fibers and, in aerobic muscle, C/F increases to values that minimize diffusion distances during normal maturation limiting further capillary growth as an adaptive mechanism for decreasing diffusion distances. study was supported in part by the National Institutes of Health Division of Research Resources, Biomedical Research Grant RR07013-20 and Public Health Services Grant HL32894. Acknowledgemenu-This
861
Kayar S. R., Archer P. G., Lechner A. J. and Banchero N. (1982) Evaluation of the concentric circles method for estimating capillary-tissue diffusion distances. Microvasc. Res. 24, 342-353.
Kayar S. R. and Banchero N. (1983) Distribution of capillaries and diffusion distances in guinea pig myocardium. Pfltigers Arch. 396, 350-352. Kayar S. R. and Banchero N. (1984) Volume overload hypertrophy elicited by cold and.its effects on myocardial cauillaritv. Pfl&ers Arch. 404. 319-325. Kay& S. R: anh ganchero N. (1485) Myocardial capillarity in acclimation to hypoxia. Pfliigers Arch. 404, 319-325. Kety S. S. (1957) Determinants of tissue oxygen tension. Fedn Proc. Fedn Am. Sots exp. Biol. 16, 666-670.
Krogh A. (19 19) The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue. J. Physiol. 52,409-41X Martini J. and Honig C. R. (1969) Direct measurement of intercapillary distance in beating rat heart in situ under various conditions of 0, supply. Microvosc. Res. 1, 244256.
Pietschmann M. and Bartels H. (1985) Cellular hyperplasia and hypertrophy, capillary proliferation and myoglobin concentration in the heart of newborn and adult rats at high altitude. Respir. Physiol. 59, 347-360. Pietschmann M.. Bartels H. and Fons R. 11982) Caoillarv supply of heart and skeletal muscle of‘smail bais ad non-flying mammals. Respir. Physiol. 50, 267-282. Plyley M. J. and Groom A. C. (1975) Geometrical distribution of capillaries in mammalian striated muscle. Am. J. Physiol. 28, 13761383.
REFERENCES
Appell H. J. (1978) Capillary density and patterns in skeletal muscle. III. Changes of the capillary pattern after hypoxia. Pfltigers Arch. 377, R-53. Aquin L. and Banchero N. (1981) The cytoarchitecture and capillary supply in the skeletal muscle of growing dogs. J. Anat. 132, 341-346.
Aquin L., Sillau A. H., Lechner A. J. and Banchero N. (19801 Growth and skeletal muscle vascularity in the guinea pig. Microvasc. Res. 20, 41-50. Banchero N. (1982) Long term adaptation of skeletal muscle capillarity. Physiologist 25, 385-389. Brown M. D., Cotter M. A., Hudlicka 0. and Vrbrova G. (1976) The effects of different patterns of muscle activity on capillary density, mechanical properties and structure of slow and fast rabbit muscles. Pfliigers Arch. 361, 241-250. Cassin S. R., Gilbert D., Bunnell C. F. and Johnson E. M. (1971) Capillary development during exposure to chronic hypoxia. Am. J. Physiol. 220, 448-451. Cotter M., Hudlicka 0. and Vrbrova G. (1973) Growth of capillaries during long-term activity in skeletal muscle. Biblphy Anot. 11, 395-398.
Goldspink G. (1972) Postembryonic growth and differentiation of striated muscle. In The Structure and Function of Muscle (Edited by Boume G. H.), pp. 179-236. Academic Press, New York. Greig-Smith P. (1957) Quanfitotive Plant Ecology. Academic Press, New York. Henquell L., Odoroff C. F. and Honig C. R. (1977) Intercapillary distances and capillary reserve in hypertrophied rat hearts beating in sifu. Circulation Res. 41, 400-408. Hudlicka 0. (1984) Develoument of the microcirculation: capillary grbwth’and adaptation. In Handbook of Physiology, Section 2, Vol. IV, part 1 (Edited by Renkin E. M. and Michel C. C.), __ pp. 165-216. American Physiological Society, Bethesda, Maryland. Jackson C. G. R.. Sillau A. H. and Banchero N. (1985) Skeletal muscle ‘fiber composition in guinea pigs ‘au% mated to cold and hypoxia. Fedn Proc. Fedn Am. Sots exp. Biol. 44, 1564.
Rakusan K. (1971) Quantitative morphology of capillaries of the heart. Meth. Arch&v. exp. Path. 5, 272-286. Ripoll E., Sillau A. H. and Banchero N. (1979) Changes in the capillarity of skeletal muscle in the growing rat. Ppiigers Arch. 380, 153-158.
Schmidt-Nielsen K. and Pennycuik P. (1961) Capillary density in mammals in relation to body size and oxygen consumption. Am. J. Physiol. 200, 746750. Sillau A. H. and Banchero N. (1977) Effects of hypoxia on capillary density and fiber composition in rat skeletal muscle. Pjtigers Arch. 370, 227-232. Sillau A. H., Aquin L., Bui M. V. and Banchero N. (1980) Chronic hypoxia does not affect Guinea Pig skeletal muscle capillarity. PjUgers Arch. 386, 39-45. Snvder G. (1987) Muscle capillarity in chicks following hypoxia. (?ornp. Biochem. ihysiol.-(in press). Snvder G. K.. Bvers R. L. and Ka&r S. R. (1984) Effects of hypoxia ‘on-tissue capillarity ii geese. R&pir.‘Physiol. 58, 151-160.
Snyder G. K., Wilcox E. E. and Bumham E. W. (1985) Effects of hypoxia on muscle capillarity in rats. Respir. Physiol. 62, 135-140. Spalteholz W. (1888) Die Verteilung der Blutgefasse im Muskel. Abe Sachs Gesch. Wiss. Math. Phys. KI. 14, 509-528.
Tenney S. M. (1974) A theoretical analysis of the relationship between venous blood and mean tissue oxygen pressures. Respir. Physiol. 20, 283-296. Thews G. (1962) Die Sauerstoffdrucke im Herzmuskelgewebe.‘Pfl&ers
Arch. 276, 16618 1.
Turek Z.. Grandtner M. and Kreuzer F. (1972) Cardiac hypertriphy, capillary and muscle fiber iensiiy, muscle fiber diameter, capillary radius and diffusion distance in the mvocardium of arowina rats adapted to a simulated altitude of 35OOm. *tigers Arch. 3%, 19-28. Turek Z. and Rakusan K. (19811 Loanormal distribution of intercapillary distance ih normal-and hypertrophic rat heart as estimated by the method of concentric circles: Its effect on tissue oxygenation. P@gers Arch. 391, 17-21. Weibel E. R. (1969) Stereological principles for morphometry in__electron microscopic cytology. Int. Rev. _ __ _ _^_ Cytol. 26, 235-302.
0
Printed in Great Britain
0300-9629/87 $3.00 + 0.00 1987 PergamonJournalsLtd
CAPILLARY GROWTH AND DIFFUSION DISTANCES IN MUSCLE GREGORYK. SNYDER Department of Biology, Box 334, University of Colorado, Boulder, CO 80309, USA (Received 22 October 1986)
Abstract-1. Tissue capillatity in muscle was modelled as square-ordered arrays with capillary-to-fiber ratios (C/F) from 0.5 to ‘infinity’. 2. C/F up to two had marked effects on diffusion distances, but C/F above had only slight effects on average distances and almost no effect on maximal distances. 3. Capillary growth during normal maturation results in C/F around two. Thus, capillary growth in adult muscle may not be an adaptive mechanism for reducing diffusion distances.
INTRODUCI’ION
Capillary growth is generally considered an effective mechanism for reducing diffusion distances to compensate changes in tissue oxygen demands or tissue oxygen supply (Krogh, 1919; Kety, 1957; Turek er al., 1972; Tenney, 1974; Banchero, 1982; Hudlicka, 1984). However, recent studies show that capillaries may not be produced in muscle following exercise or hypoxia (Cassin et al., 1971; Sillau and Banchero, 1977; Appell, 1978; Sillau et al., 1980; Pietschmann and Bartels, 1985; Snyder et al., 1985). Therefore, the relationships between capillary growth and tissue oxygenation may be more complicated than previously throught. The purpose of this report is to provide a quan-
titative estimate of the relationships between capillary growth and diffusion distances in muscle. The results show that there is a limit to the benefit of increasing capillarity, reached at capillary-to-muscle fiber ratios (C/F) around two. Additional capillaries beyond two per fiber do not decrease diffusion distances into the cell interior. MATERIALS
AND METHODS
Kayar er al. (1982) developed a series of models to describe the relationships of capillarity and diffusion distances in normal adult muscle. These models are extended to include the effects of capillary growth on diffusion distances. Capillaries were arranged as. points in squareordered arrays with the capillary-to-fiber ratios (C/F) preset at values ranging from 0.5 to ‘infinity’; in the latter case, when the entire perimeter of each fiber was filled with capillaries. I selected the square-ordered array because a number of studies have shown that it accurately reflects tissue capillarity in adult muscle (Schmidt-Nielsen and Pennycuik, 1961; Plyley and Groom, 1975; Kayar and Banchero, 1983). In addition, similar results are obtained using other models. Initially, fibers of different sizes were used. However, fiber size did not a&t the outcome of the results. Therefore, the final models were based on fibers assigned an arbitrary dimension of 1 unit squared. Since the capillaries were drawn as points, the dimensions of the capillaries themselves did not contribute to diffusion distances. However, the positions of the capillaries contributed to the distances measured. Therefore, the results are
based on capillary positions that minimized distances into individual fibers. Finally, capillarity is equated to C/F since other measures such as capillary density (CD) and the numbers of capillaries around each fiber (CAF) were not consistent indicators of capillarity; e.g. when C/F is one, CAF may be 2 or 4. Distances were measured from 100 points set within each fiber to the capillary closest to each point (Thews, 1962; Martini and Honig, 1969). The points assigned to each fiber were set at fixed intervals along grid lines oriented randomly to the capillaries (Weibel, 1969). This ‘systematic’ approach to sampling the distances is generally accepted as preferable to a “nonrepresentative sampling from a failed attempt at random sampling” (Greig-Smith, 1957; Kayar er al., 1982). Diffusion distances are expressed as the cumulative frequency distribution of the measured distances. This ap preach provides a simple means of calculating the probability that any given area of tissue within individual muscle fibers will be within a given distance of a capillary. RESULTS
When C/F is increased from 0.5 to 2.0, average diffusion distance decreased by 55% and maximal diffusion distance (FQ, in Fig. 1) decreased by 64%. However, when C/F was increased from 2.0 to ‘infinity’ the average distance decreased by 50% and the maximal distance by 19%. Thus, the benefit of completely surrounding each fiber with capillaries on the average distance is less than when C/F was increased from 0.5 to 2.0 and for the maximal distance, there is essentially no benefit at all. It is also notable that at lower C/F adding capillaries has the greatest effect on longer distances whereas at higher C/F adding capillaries reduces the shorter, but not the longer, distances (Fig. 1). DISCUSSION
Normal growth in muscle, which occurs by hypertrophy of existing fibers rather than addition of new fibers to the muscle bed (Goldspink, 1972; Sillau and Banchero, 1977; Rip011 et al., 1979), has two important consequences for an understanding of the benefits of capillary growth. First, increased fiber cross sectional area (FCSA) associated with growth 859
GREGORY
Distance
Fig. 1. Cumulative frequency distribution of distances from 100 points distributed uniformly through a muscle fiber to the capillary nearest to each point when the capillary-tofiber ratio is increased from OS to ‘infinity’; in the latter case, when the perimeter of the fiber is filled with capillaries. Note the arrow indicating the 95% frequency which, for convenience, is taken as the maximal diffusion distance into the muscle fiber. Note also that distance refers to the relative length of one side of the fiber; e.g. a distance of 0.5 is SO% of the distance along one side of the fiber or one-half of the square root of the cross sectional area of the fiber. capillaries apart, increasing diffusion distances. Second, preservation of diffusion distances during normal maturation or decreasing diffusion distances to compensate changes in oxygen supply occurs by addition of new capillaries to the perimeters of existing fibers. The results presented here show that adding capillaries, up to two per fiber is an effective mechanism for decreasing diffusion distances. However, adding capillaries beyond two per fiber does not reduce diffusion distances into the centers of fibers; the distance that appears to be the most critical for aerobic metabolism (Henquell et al., 1977). In other words, there may be a ‘design limitation’ to the geometric architecture of microvascular beds in muscle. The effects of this ‘design limitation’ are shown in Fig. 2 where the relationship between FCSA and C/F is plotted for four different muscles (continuous lines) and, from Fig. 1, the expected relationships of FCSA and C/F that will keep 95% of the muscle fibers within the same distance; e.g. keep maximal diffusion distances constant (dashed lines). For aerobic skeletal muscle in dogs and cardiac muscle in rodents, increased FCSA appears to be coupled to increased C/F to keep diffusion distances constant. However, for skeletal muscle in rodents, increased FCSA is greater than can be satisfied by increased C/F and diffusion distances increase with age. The data as presented in Fig. 2 illustrate a number of key features of the relationships between capillary growth and diffusion distances in muscle. For example, the shorter diffusion distances in the more highly pushes
K.
SNYDER
aerobic muscle, the heart, are due to the inclusion of more fibers with smaller FCSA rather than increasing C/F (Fig. 1). This pattern is consistent with capillarity in mammalian muscle generally where there are marked differences in CD and diffusion distances, but only limited differences in C/F (Schmidt-Nielsen and Pennycuik, 1961; Plyley and Groom, 1975; Hudlicka, 1984); the highest reported CD is for shrew, Suncus etruscus, papillary muscle, CD = 7287 caps/mm’ and the lowest is for rabbit gastrocnemius, CD = 341 caps/mm2 (Plyley and Groom, 1975; Pietschmann et al., 1982). The C/F for these two muscles, 1.7 caps/fiber, are identical. The differences in CD are due entirely to FCSA, 240,um2 for the shrew and 4785 pm2 for the rabbit. It is also apparent that the extent to which muscles can increase in size via hypertrophy and keep diffusion distances constant is limited and more apparent in the muscles with smaller ‘initial FCSA. Thus, from an FCSA associated with C/F = 0.5, fibers can increase about eight-fold in cross sectional area when C/F is increased to 2.0 (Fig. 2). Finally, C/F in adult muscles approach values that provide a maximal benefit to diffusion distances; capillary growth during normal maturation may result in C/F that represent the upper limit for reducing diffusion distances. Therefore, hypoxia, etc. may not result in capillary growth in adult muscle because there is no gas transport benefit to be derived from the additional capillaries. This scenario of a limited benefit to capillary growth is consistent with results from a wide variety of studies and may explain why: (1) cardiac hypertrophy in adult animals is not attended by the development of new capillaries (Henquell et al., 1977; Turek and Rakusan, 1981); (2) hypoxia DOG
5.0': 0 x NE 4or 9 CI
?! a
3.01
I-_
0
Capillaries
per Fiber
Fig. 2. Relationship of fiber cross sectional area (FCSA) and number of capillaries per fiber (C/F) in four muscles (continuous lines) and, from Fig. 1, the relation of FCSA and C/F necessary to keep the maximal diffusion distances (R& in the muscle constant. The bs is 23.2 pm for dog, 17.4 pm for guinea pig skeletal muscle, and 11.3 pm for guinea pig cardiac muscle. Data from Aquin er al., 1980; Aquin and Banchero, 1981; Kayar and Banchero, 1984.
Capillarity and diffusion distances
results in the development of new capillaries in the myocardium of young rats, but the differences between experimentals and controls disappear as myofibers grow past normal adult values (Kayar and Banchero, 1985); (3) severe hypoxia per se may not stimulate capillary growth in skeletal muscle (Cassin et al., 1971; Turek et al., 1972; Sillau and Banchero, 1977; Appell, 1978; Snyder et al., 1985) and (4) capillary growth in adult skeletal muscle is limited to muscles containing primarily fibers low on oxidative capacity with low initial C/F and the resulting C/F may approach, but do not exceed, C/F in oxidative fibers of control animals (Cotter et al., 1973; Brown et al., 1976; Jackson ef al., 1985; Snyder, et al., 1984; Snyder, 1987). In conclusion, there is limited potential for decreasing diffusion distances in muscle because capillaries are added to the perimeters of existing fibers and, in aerobic muscle, C/F increases to values that minimize diffusion distances during normal maturation limiting further capillary growth as an adaptive mechanism for decreasing diffusion distances. study was supported in part by the National Institutes of Health Division of Research Resources, Biomedical Research Grant RR07013-20 and Public Health Services Grant HL32894. Acknowledgemenu-This
861
Kayar S. R., Archer P. G., Lechner A. J. and Banchero N. (1982) Evaluation of the concentric circles method for estimating capillary-tissue diffusion distances. Microvasc. Res. 24, 342-353.
Kayar S. R. and Banchero N. (1983) Distribution of capillaries and diffusion distances in guinea pig myocardium. Pfltigers Arch. 396, 350-352. Kayar S. R. and Banchero N. (1984) Volume overload hypertrophy elicited by cold and.its effects on myocardial cauillaritv. Pfl&ers Arch. 404. 319-325. Kay& S. R: anh ganchero N. (1485) Myocardial capillarity in acclimation to hypoxia. Pfliigers Arch. 404, 319-325. Kety S. S. (1957) Determinants of tissue oxygen tension. Fedn Proc. Fedn Am. Sots exp. Biol. 16, 666-670.
Krogh A. (19 19) The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue. J. Physiol. 52,409-41X Martini J. and Honig C. R. (1969) Direct measurement of intercapillary distance in beating rat heart in situ under various conditions of 0, supply. Microvosc. Res. 1, 244256.
Pietschmann M. and Bartels H. (1985) Cellular hyperplasia and hypertrophy, capillary proliferation and myoglobin concentration in the heart of newborn and adult rats at high altitude. Respir. Physiol. 59, 347-360. Pietschmann M.. Bartels H. and Fons R. 11982) Caoillarv supply of heart and skeletal muscle of‘smail bais ad non-flying mammals. Respir. Physiol. 50, 267-282. Plyley M. J. and Groom A. C. (1975) Geometrical distribution of capillaries in mammalian striated muscle. Am. J. Physiol. 28, 13761383.
REFERENCES
Appell H. J. (1978) Capillary density and patterns in skeletal muscle. III. Changes of the capillary pattern after hypoxia. Pfltigers Arch. 377, R-53. Aquin L. and Banchero N. (1981) The cytoarchitecture and capillary supply in the skeletal muscle of growing dogs. J. Anat. 132, 341-346.
Aquin L., Sillau A. H., Lechner A. J. and Banchero N. (19801 Growth and skeletal muscle vascularity in the guinea pig. Microvasc. Res. 20, 41-50. Banchero N. (1982) Long term adaptation of skeletal muscle capillarity. Physiologist 25, 385-389. Brown M. D., Cotter M. A., Hudlicka 0. and Vrbrova G. (1976) The effects of different patterns of muscle activity on capillary density, mechanical properties and structure of slow and fast rabbit muscles. Pfliigers Arch. 361, 241-250. Cassin S. R., Gilbert D., Bunnell C. F. and Johnson E. M. (1971) Capillary development during exposure to chronic hypoxia. Am. J. Physiol. 220, 448-451. Cotter M., Hudlicka 0. and Vrbrova G. (1973) Growth of capillaries during long-term activity in skeletal muscle. Biblphy Anot. 11, 395-398.
Goldspink G. (1972) Postembryonic growth and differentiation of striated muscle. In The Structure and Function of Muscle (Edited by Boume G. H.), pp. 179-236. Academic Press, New York. Greig-Smith P. (1957) Quanfitotive Plant Ecology. Academic Press, New York. Henquell L., Odoroff C. F. and Honig C. R. (1977) Intercapillary distances and capillary reserve in hypertrophied rat hearts beating in sifu. Circulation Res. 41, 400-408. Hudlicka 0. (1984) Develoument of the microcirculation: capillary grbwth’and adaptation. In Handbook of Physiology, Section 2, Vol. IV, part 1 (Edited by Renkin E. M. and Michel C. C.), __ pp. 165-216. American Physiological Society, Bethesda, Maryland. Jackson C. G. R.. Sillau A. H. and Banchero N. (1985) Skeletal muscle ‘fiber composition in guinea pigs ‘au% mated to cold and hypoxia. Fedn Proc. Fedn Am. Sots exp. Biol. 44, 1564.
Rakusan K. (1971) Quantitative morphology of capillaries of the heart. Meth. Arch&v. exp. Path. 5, 272-286. Ripoll E., Sillau A. H. and Banchero N. (1979) Changes in the capillarity of skeletal muscle in the growing rat. Ppiigers Arch. 380, 153-158.
Schmidt-Nielsen K. and Pennycuik P. (1961) Capillary density in mammals in relation to body size and oxygen consumption. Am. J. Physiol. 200, 746750. Sillau A. H. and Banchero N. (1977) Effects of hypoxia on capillary density and fiber composition in rat skeletal muscle. Pjtigers Arch. 370, 227-232. Sillau A. H., Aquin L., Bui M. V. and Banchero N. (1980) Chronic hypoxia does not affect Guinea Pig skeletal muscle capillarity. PjUgers Arch. 386, 39-45. Snvder G. (1987) Muscle capillarity in chicks following hypoxia. (?ornp. Biochem. ihysiol.-(in press). Snvder G. K.. Bvers R. L. and Ka&r S. R. (1984) Effects of hypoxia ‘on-tissue capillarity ii geese. R&pir.‘Physiol. 58, 151-160.
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