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The John B. Pierce Laboratory and Department of Chemical Engineering, Yale University, New Haven, Connecticut 06519
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Emerson, Geoffrey G., and Steven S. Segal. Alignment of
microvascular units along skeletal muscle fibers of hamster retractor.
J. Appl. Physiol. 82(1): 42-48, 1997.
When muscle fibers contract, blood flow requirements increase
along their entire length. However, the organization of capillary
perfusion along muscle fibers is unclear. The microvascular unit (MVU)
is defined as a terminal arteriole and the group of capillaries it
supplies. We investigated whether neighboring MVUs along the fiber axis perfused the same group of muscle fibers by using the parallel-fibered retractor muscle. Hamsters were anesthetized and perfused with Microfil
to visualize MVUs relative to muscle fibers. Fields of study, which
encompassed five to seven neighboring MVUs along a muscle fiber, were
chosen from the interior of muscles and along muscle edges. On average,
MVUs were 1 mm in length, 0.50 mm in width, and 0.1 mm deep; segments
of ~30 fibers were contained in this tissue volume of 0.05 mm3 (20 MVUs/mg muscle). The total
distance across muscle fibers encompassed by a pair of MVUs is
designated "union" (U); the fraction of this distance common to
both MVUs is designated "intersection" (I). The ratio of I to U
for the widths of neighboring MVUs provides an index of MVU alignment
along muscle fibers (e.g., I/U = 1.0 indicates complete alignment,
where the fibers perfused by one MVU are the same as those perfused by
the neighboring MVU). We found that I/U along muscle edges (0.71 ± 0.02) was greater (P < 0.05) than
the ratio measured within muscles (0.66 ± 0.02). A model predicted
a maximum I/U of 0.58 with random MVU alignment. Thus measured values
were closer to random than to complete alignment. These findings
indicate that an increase in blood flow along muscle fibers requires
the perfusion of many MVUs and imply that vasodilation is coordinated
among the parent arterioles from which corresponding MVUs
arise.
arteriole; capillary; functional unit; local flow control; microcirculation
INTRODUCTION EXERCISE is the preeminent stimulus for increasing the
activity of both skeletal muscle and the cardiovascular system. In response to exercise, blood flow to active muscles increases in proportion to the metabolic requirements of the respective muscle fibers (12, 15, 21). Indeed, the functional hyperemia and oxygen
consumption of exercising muscle can exceed resting values by 50-fold
(1, 12). The strong linear relationships among muscle work, oxygen
consumption, and muscle blood flow manifested in humans (1), animals
(12, 17), and isolated muscle preparations (15) imply a coupling
between muscle fiber activity and microvascular perfusion.
Nevertheless, a major gap exists in our understanding of how the
controlled units of each system (i.e., muscle fibers and capillaries)
interact with each other.
In skeletal muscle, a terminal arteriole (TA) gives rise to groups of
20-30 capillaries that run parallel to muscle fibers for a
distance of ~1 mm (3, 6, 14). When a TA constricts or dilates, flow
through all of its capillaries diminishes or increases, respectively
(22, 23, 29). Because this functional unit is the smallest element of
control for capillary perfusion in skeletal muscle (3, 6), it is
referred to hereafter as a microvascular unit (MVU). This organization
of capillary groups into MVUs is apparent in skeletal muscles from
amphibians to primates (9, 10, 14, 19, 25, 28). TAs also control the
flow of red blood cells into capillary groups in the saclike cremaster muscle (2, 22), which has a diverse orientation of both muscle fibers
and capillaries.
The millimeter distance spanned by each MVU is considerably less than
the length of skeletal muscle fibers, which often span many
centimeters. Based on a compilation of histological and morphometric data, it was assumed that blood flow to the volume of muscle supplied by an MVU could be controlled independent of blood flow to the rest of
the muscle (3). However, when a muscle fiber (or fiber group)
contracts, it is metabolically active along its entire length and will
require blood flow through the MVUs that supply corresponding segments
of the fiber(s). The precision with which blood flow can be selectively
controlled to a particular fiber (or fiber group; Ref. 4) will
therefore depend on the alignment of the corresponding MVUs; if the
MVUs encompass different fibers or fiber groups, there may be a
mismatch between local requirements of muscle fibers and the
capillaries actually perfused. This basis for blood flow heterogeneity
(7) has not been previously examined.
In this study, we have used the parallel-fibered hamster retractor
muscle (16, 20, 26) to test the hypothesis that the group of muscle
fibers perfused by one MVU is the same group of fibers perfused by
neighboring MVUs positioned along the muscle fibers. Our data shed new
light on two fundamental questions. First, are MVUs aligned along the
muscle fibers they supply? Second, is there a correspondence among the
parent vessels that gives rise to MVUs that supply a muscle fiber or
fiber group?
METHODS All procedures were approved by the Animal Care and Use Committee of
the John B. Pierce Laboratory and were performed in accord with the
Guiding Principles in the Care and Use of Animals of the American
Physiological Society.
Vascular casting. Male golden hamsters
(n = 8, 106 ± 5 g; Charles River
Breeding Laboratories) were anesthetized (pentobarbital sodium; 65 mg/kg ip). A tracheotomy was performed to ensure airway patency, and
the left femoral vein was catheterized (PE-50) for infusing additional
anesthetic (10-15 mg/kg) as needed. The abdominal aorta was
cannulated retrogradely with PE-50 tubing, with the tip advanced just
rostral to the diaphragm. The hamster was given an overdose of
pentobarbital sodium intravenously, the vena cava was punctured for
effluent, and 10 ml of Microfil casting compound (Flow-Tek) was infused
into the abdominal catheter. The hamster was then stored at 4°C.
Within 1-2 days after casting, retractor muscles were exposed and
examined with a stereo microscope (model SV8, Zeiss) for uniformity of
Microfil perfusion, and muscle length was measured from its caudal
origin on the thoracic vertebrae to its rostral insertion on the cheek
pouch (20). Muscles were carefully excised, trimmed of superficial
connective tissue, pinned at in situ length in a petri dish coated with
Sylgard (Dow Corning), and then stored at 4°C in 50% glycerin to
preserve and clear the tissue (18).
Videomicroscopy. To highlight MVUs and
arteriolar branches, retractor preparations were placed on the stage of
an inverted microscope (Nikon Diaphot) and transilluminated with a
100-W halogen lamp (condenser numerical aperture, 0.52).
Oblique epi-illumination from a 30-W fiber-optic lamp (Dolan-Jenner)
highlighted the microvascular cast. Casts were examined at ×25
total magnification (×10 eyepieces; ×2.5/0.08 objective,
Zeiss) to determine suitable areas of study (see Study
fields). Then, with a ×4/0.13
objective (Nikon), images were focused onto a video camera (model
IK-C30A CCD, Toshiba) coupled to a monochrome monitor (model PVM-122,
Sony); total magnification on the monitor face was ×58. Video
prints (model UP-870MD, Sony) were assembled to form a montage of the
field under study. All measurements were calibrated with reference to
stage micrometer (100 × 0.01 = 1 mm; Graticules).
Characterization of arterioles.
Primary (1A) arterioles were designated as those segments that arose
directly from feed arteries as they entered the muscle (16).
Second-order (2A) arterioles typically run parallel to muscle fibers
and serve as the principle distribution vessels. Branches from 2A
arterioles were characterized as defined in
RESULTS. Segment lengths between
branches were measured along 2A and third-order (3A) arterioles (30) by
using the eyepiece reticule; branch angles were measured with a
protractor positioned on the video monitor (16).
Study fields. Each study field was 1 × 5 mm (width × length; Fig.
1); resolution of neighboring MVUs along
the axis of a group of parallel muscle fibers was the principle
criterion for field selection. Regions in which the Microfil casting
was sparse were avoided, as were regions in which the casting was too
dense to distinguish MVUs from each other. Each study field encompassed five to seven MVUs that intersected a 4-mm reference line oriented parallel to muscle fibers. On gross visual inspection, arteriolar network topology differed noticeably between the caudal and rostral regions of the muscle. Consequently, three study fields (from within
the caudal, middle, and rostral one-third of muscle length) were
selected for each of five muscles. To test for an effect of anatomic
boundaries, study fields were also sampled along the edges of four
additional muscles from respective regions. Each MVU in a study field
was traced back to the 2A branch from which it originated.
MVU perfusion fields. The boundaries
of each MVU in the study field were measured at ×100
magnification (×10/0.25 objective, Zeiss) with reference to a
reticule in the eyepiece. Boundaries were defined on the montage of the
study field; focusing through the MVU ensured that the capillaries in
each MVU were fully accounted for. Perpendicular to muscle fibers, the
most proximal and distal capillaries originating from a TA defined MVU
width; the caudal and rostral MVU boundaries were positioned coincident
with the termination of Microfil in the capillaries (Fig. 1). Although the lack of complete filling facilitated the resolution of respective MVUs within a study field, it prevented resolution of the total distance spanned by the respective MVUs in vivo. Therefore, our measurement of MVU alignment is based on MVU width, which corresponds to the group of muscle fibers perfused by the capillaries originating from a defined TA. Additionally, in each muscle region, the span of
individual MVUs that had complete filling was measured as the distance
between the collecting venules originating in either direction from the
capillaries perfused by a common TA (6).
MVU alignment. The alignment of MVUs
along muscle fibers in each study field was characterized as follows:
the total distance across muscle fibers encompassed by a pair of MVUs
was designated "union" (U); the fraction of this distance common
to both MVUs was designated "intersection" (I) (see Fig. 1). The
alignment of MVUs along muscle fibers in each study was characterized
by measuring the I and U of MVU widths for MVU pairs. In practice, the
ratio of I to U provides an index of the alignment between two MVUs; a
value of 1.0 indicates that the two MVUs feed the same group of muscle
fibers, a value of 0 indicates that the two MVUs have no fibers in
common, and values between 0 and 1 indicate that the two MVUs supply
some common fibers but also supply fibers that are not common to both
MVUs. Within each study field, I/U was determined for adjacent MVU
pairs and for MVU pairs separated by one, two, or three MVUs. Adjacent
MVUs are referred to as a 1° pair; the latter are referred to as
2°, 3°, and 4° pairs, respectively. The mean distance
between the midpoint of neighboring MVUs was calculated from the number
of MVUs along the 4-mm reference line.
Model. A computer model was developed
to determine the maximum I/U value for randomly placed rectangles. The
widths of the rectangles used in the simulation had a normal
distribution with the same mean width and SD as we obtained for MVUs
sampled in the retractor muscle. For each trial of the simulation, a
reference rectangle was selected randomly from the sample and its lower left corner was placed at the origin of a two-dimensional axis. A test
rectangle, also selected at random from the population, was then
positioned to the right of the reference. The vertical position of the
base of the test rectangle was randomly determined, with equal
probability of it being placed anywhere within ±1 width of the
reference rectangle. Two other test rectangles were then randomly
selected and positioned directly above and below the first test
rectangle to form a vertical column of three contiguous rectangles
adjacent to the reference. The I/U value was calculated for each of the
test rectangles relative to the reference, then the largest I/U value
of the three was stored. This process was repeated for 8,000 trials,
and the mean value was taken as the predicted maximal value of I/U for
randomly arranged rectangles.
Statistics. Data were compiled and
analyzed with Microsoft Excel (version 5.0, personal computer). Summary
data are presented as means ± SE. Comparisons of I/U values among
muscle regions (e.g., caudal vs. middle vs. rostral; muscle interior
vs. muscle edge) and among MVU pairs (1°, 2°, 3°, and
4°) were performed with analysis of variance. Measured I/U values
were compared with values generated by an equivalent number of trials
from the computer model by using a
t-test. Results were accepted as
statistically significant at P RESULTS General features of retractor muscle and its vascular
supply. The hamster retractor muscle is of mixed fiber
composition (27) and functions to retain the cheek pouch against the
body wall (20). The muscles we studied were 30-35 mm in length in
vivo; they were ~500 µm thick and ~5 mm wide at the origin and
through the midregion, from where they fanned out and became thinner
( MVUs in retractor muscles. Figure 1
illustrates the analysis developed for evaluating MVU widths and I/U
values. The present I/U data are based on 20 study fields examined in
nine muscles. The average distance between neighboring MVUs (0.64 ± 0.01 mm) indicates that ~50 MVUs were required to span the length of
retractor muscles. The tracings in Fig. 2
illustrate that MVUs arising from a parent arteriole can range from
poorly aligned (Fig. 2A) to well
aligned (Fig. 2B) along muscle
fibers.
The distribution of MVU widths appeared Gaussian (Fig.
3A). On
average, the width of MVUs was 0.50 ± 0.01 mm
(n = 111), and MVUs perfused segments
of ~30 muscle fibers through 2-3 layers (tissue depth, ~100
µm); these features did not differ
(P = 0.10) across the caudal, middle,
and rostral regions of the retractor muscle. The average muscle fiber
length spanned by individual MVUs with complete filling was 0.93 ± 0.07 mm. Thus with MVU dimensions of 0.5 × 0.1 × 1.0 mm
(width × depth × length), we estimated that the average
volume of muscle supplied by a single MVU was 0.05 mm3, which predicts that each
milligram of muscle contains ~20 MVUs.
The distribution for I/U values was skewed toward the higher end (Fig.
3B), with I/U values in respective
muscle regions ranging from 0.06-0.99 (caudal), 0.40-0.91
(middle), and 0.24-0.93 (rostral). The I/U values were not
different among regions (P = 0.06),
with an overall average of 0.66 ± 0.02. However, values from the
interior of muscles were less (P < 0.05) than I/U values determined along the edge of muscles (0.71 ± 0.02), supporting the idea that a physical boundary can influence MVU
alignment. Irrespective of muscle region, the alignment of MVUs within
study fields did not vary with separation between MVUs (Fig.
4).
In approximately one-half of the study fields examined, all MVUs within
the field originated from the same parent arteriole (Fig.
2B). In the remaining fields, the
TAs that supplied MVUs originated from more than one parent vessel
(e.g., Fig. 1B). The alignment of
MVUs was not different (P = 0.13)
between such networks, which were found, irrespective of muscle region.
Computer model. The model randomly
selected rectangles from a normal distribution of rectangles having the
same mean width and SD as MVUs in retractor muscles. The assumption of
a normal distribution is consistent with the data in Fig.
3A. The model simulated alignment in
two dimensions only and assumed that muscle fibers were parallel, as
observed in our study fields of retractor muscles. The model also
assumed that there were no gaps in tissue perfusion between neighboring
MVUs, which is the case in vivo (3, 6). Lastly, the model chose the
neighboring MVU with maximum overlap in each trial; this feature was
designed to provide an estimate of the maximum value that could be
expected for random alignment across a large number of samples. The
model predicted that random MVU alignment would result in a maximum I/U
value of 0.58, which was less (P < 0.05) than the average value observed throughout the retractor muscle.
Because complete alignment of MVUs is indicated when I/U = 1.0 and our
measured values were consistently closer to the predicted value, we
suggest that the organization of MVUs in the retractor muscle is closer
to random than to completely aligned.
DISCUSSION When a muscle fiber becomes active, its requirements for oxygen
delivery and metabolite removal increase along its entire length.
However, muscle fibers are much longer than the distance supplied by
the capillaries in a single MVU. Therefore, blood flow must increase
through many MVUs to perfuse the entire length of a muscle fiber. The
accuracy with which blood flow can be controlled to a particular fiber
(or to a group of fibers) is determined by how precisely MVUs are
aligned along the muscle fiber(s). We have performed the first
investigation of this relationship in the parallel-fibered retractor
muscle of the hamster. Our analysis used the I/U of neighboring MVU
widths as an index of MVU alignment (Fig. 1). Complete alignment is
indicated by an I/U of 1.0 (i.e., MVUs within a study field overlay the
same group of muscle fibers), whereas random alignment was predicted to
result in a maximum ratio of 0.58. In practice, we found that I/U
values were 1) closer to the value
predicted by the random model; 2)
independent of separation between MVUs (Fig. 4);
3) similar across muscle regions with pronounced differences in arteriolar network topology; and 4) greater along muscle edges than
within the muscle. Moreover, MVUs within a study field were as often
derived from different parent vessels as from the same parent vessel.
These findings imply that blood flow cannot selectively increase to a
specific muscle fiber or to a particular group of fibers. Rather, blood flow must increase along a relatively wide region of the muscle relative to the locus of muscle fiber activity. Furthermore,
vasodilation must encompass multiple parent vessels to increase
capillary perfusion along the active muscle fibers.
The average distance between the midpoint of neighboring MVUs was 0.64 mm, whereas the total distance spanned by completely filled MVUs was
~1 mm. This difference implies that there is a degree of overlap
among MVUs through fiber layers (i.e., muscle thickness) of the
retractor (as found in the hamster tibialis muscle; Ref. 6) that was
not accounted for in our two-dimensional analysis of study fields.
Nevertheless, our findings indicate that The branching of arteriole networks does not consistently follow the
organization of muscle fibers, whether fibers are arranged in parallel
(e.g., retractor muscle) or have a dispersive organization (e.g.,
cremaster muscle). Thus the arteriolar network may appear ill-suited to
provide blood flow specifically in accord with muscle fiber activity.
This impression is highlighted by our finding that
1) the MVUs within a study field
were often supplied by different parent arterioles and
2) the proximal and distal regions
of the retractor muscle are typically supplied by different feed
arteries (16), as seen in other skeletal muscles (30). Moreover, this organization of the resistance network implies that, for capillary perfusion to increase along the length of a muscle, a mechanism is
required whereby blood flow into respective MVUs is physiologically coordinated among the parent arterioles. In fact, evidence suggests that cell-to-cell coupling between smooth muscle and endothelial cells
enables such coordination of vasomotor activity among arteriole branches (11, 13, 23, 24). Thus in addition to promoting a uniform
distribution of pressure and flow within the muscle (8), arteriolar
anastomoses could provide a signaling pathway for coordinating MVU
perfusion among TAs (22, 23) and respective regions of the muscle.
Testing this hypothesis will require additional experiments performed
during physiological conditions of blood flow control.
Ascertaining the uniformity of capillary perfusion along muscle fibers
will provide a functional correlate to the relationships indicated by
the present anatomic data. However, evidence from the cremaster muscle
suggests that, even with all capillaries perfused, a heterogeneous
distribution of red blood cells within each MVU will place an upper
limit on the uniformity of muscle fiber perfusion (5, 7). Nevertheless,
any overlap of diffusion fields through the thickness of the muscle
could contribute to the homogenous distribution of oxygen among muscle
fibers (6). Such an interaction seems particularly apparent in limb
muscles (e.g., the hamster tibialis; Ref. 6), which have much greater thickness compared with the retractor (16, 20, 26), cremaster (2, 22,
23), and spinotrapezius (25) muscles more commonly used for
microvascular studies. Indeed, the thinness of these latter tissues may
constrain the relationship among MVU perfusion fields to more closely
approximate a two-dimensional array.
We tested for the possibility that anatomic constraints may promote MVU
alignment along muscle fibers by comparing I/U values of MVUs located
within the muscle to those located along the edge of the muscle.
Indeed, we found significantly greater alignment in the latter case.
Separation between groups of muscle fibers could also explain the
apparently high degree of MVU alignment in the thin region of the rat
spinotrapezius muscle (25). In cases where MVUs were well aligned with
parallel parent vessels (Fig. 2B),
consecutive TA branches were of uniform length and orientation, which
may be enforced by separation between fiber groups. However,
consecutive TAs often differed in length, resulting in adjacent MVUs
with incomplete overlap (Fig. 2A).
Collectively, these findings imply that one determinant of MVU
alignment is the variability in the length of respective TAs.
Conclusion. An increase in blood flow
to an active muscle fiber without overperfusion of inactive fibers
would require MVUs to be no wider than a muscle fiber and completely
aligned along the axis of the fiber. However, the present data indicate
that neither the size nor the alignment of MVUs is conducive to
selectively increasing blood flow to a single muscle fiber, nor even to
a particular fiber group. We propose instead that capillary perfusion must increase through relatively broad regions along the muscle to
accommodate the metabolic demands of individual muscle fibers.
Fig. 1.
Analysis of microvascular unit (MVU) alignment in hamster retractor
muscle. A: line drawing of excised
retractor muscle pinned out in petri dish and filled with Microfil (as
detailed in METHODS). FA, feed
artery (2 FAs are shown giving rise to primary, second-order, and
third-order arteriolar branches within muscle); O, muscle origin
(caudal end) from spinous processes of last 3 thoracic vertebrae; I,
muscle insertion (rostral end) on fascia of cheek pouch (20). Three 1 × 5-mm study fields are indicated by rectangles drawn in rostral,
middle, and caudal regions of muscle; 2 fields are within muscle, 1 field is at muscle edge. B: boundaries
of neighboring MVUs in study field. Dark 4-mm reference line is drawn parallel to muscle fibers (not shown for clarity) and capillaries and
spans 5 MVUs. In practice, ratio of distance common to both MVUs in a
pair ("intersection"; I) to total distance across muscle fibers
encompassed by the pair ("union"; U) (I/U) was calculated for
every pair of MVUs in field of study: primary (1°) pairs consist of
adjacent MVUs (e.g., a and b, b and c, c and d, d and e); secondary (2°) pairs entail every other MVU (e.g., a and c, b and d, c and e); tertiary (3°) pairs are separated by 2 MVUs (e.g., a and d, b
and e), and quaternary (4°) pairs are separated by 3 MVUs (e.g., a
and e). In this example, there are four 1° pairs, three 2°
pairs, two 3° pairs, and one 4° pair.
C: boundaries of 1 MVU, as traced from
middle MVU illustrated in Fig. 2A.
Distance between upper (proximal) and lower (distal) boundaries
indicates MVU width. TA, terminal arteriole from which capillaries in
this MVU originate. D: I/U values for
pairs of MVUs. U and I are indicated at
left of each pair of rectangles (i.e.,
MVU boundaries). Bottom 2 examples illustrate how same I/U
value (e.g., 0.5) may result from quite different physical
relationships between neighboring MVUs.
[View Larger Version of this Image (24K GIF file)]
0.05.
200 µm) as they inserted onto the cheek pouch over a width of
10-15 mm. The mass of the retractor muscle from similar animals is
80-120 mg (S. S. Segal and D. G. Welsh, unpublished
observations). Arteriolar network topology was often
tree-like in the thick region, whereas the thin region was
characterized by many anastomosing 3A "loops" among 2A branches.
Typically, two feed arteries [in vivo diameter ~70 µm (at
rest) to ~120 µm (dilated); D. G. Welsh and S. S. Segal] entered the midregion at the medial edge of the ventral surface (see
Fig. 1 of Ref. 16) and continued for 200-400 µm as 1A arterioles within the muscle. Each 1A vessel typically gave rise to a pair of
interconnected 2A branches that coursed along the muscle axis. Daughter
branches typically arose from 2A vessels at right angles (88 ± 2°; n = 156) with an interbranch
distance of 0.41 ± 0.02 mm (n = 164) and fell into three categories:
1) TAs (~40%) of individual MVUs;
2) 3A arterioles (~35%) that
branched into two or more TAs that supplied corresponding MVUs; and
3) 3A arcade segments (~25%) that
formed anastomoses with the same or a different 2A branch and that also
gave rise to MVUs.
Fig. 2.
Line drawings (from video monitor) of MVUs containing Microfil in
hamster retractor; muscle fibers (not shown for clarity) are horizontal
and parallel to capillaries. These MVUs encompass tissue depth of
2-3 muscle fibers; drawings were made by focusing through muscle.
A: three MVUs originating from common
parent vessel with minimal overlap between MVUs arising from
consecutive TAs along parent arteriole. Note that middle MVU supplies
different group of fibers than MVUs on left and right, attributable to
different lengths of respective TA branches. With perfusion of entire
length of capillaries (as present in vivo), gap between left and right MVU would be eliminated, with respective capillaries supplying same
fibers and converging into common collecting venule (3, 6, 14).
B: adjacent rows of well-aligned MVUs
along muscle fibers, attributable to close proximity of parallel
branches of respective parent vessels and nearly uniform lengths of
respective TA branches.
[View Larger Version of this Image (36K GIF file)]
Fig. 3.
A: frequency distribution of MVU
widths (n = 111) from all study fields
examined for I/U relationships; mean MVU width was 0.50 ± 0.01 mm.
B: frequency distribution for all I/U
values calculated for study fields within hamster retractor muscles;
mean I/U was 0.66 ± 0.02.
[View Larger Version of this Image (18K GIF file)]
Fig. 4.
Alignment of MVUs along muscle fibers in 15 study fields located within
muscle (to minimize anatomic boundary effect of muscle edges). Values
are means ± SE of I/U for 1°
(n = 63), 2°
(n = 49), 3°
(n = 34), and 4°
(n = 20) pairs (see Fig.
3B) shown relative to maximum value
(dotted line) for randomly aligned MVUs (as described in
METHODS). Alignment of MVU pairs was
not significantly different across orders
(P = 0.7) and was therefore
independent of MVU separation.
[View Larger Version of this Image (16K GIF file)]
50 MVUs must work together
to increase flow to an active fiber. An insightful review (3) has
inferred that blood flow to the volume of muscle encompassed by an MVU
could be controlled independent of blood flow elsewhere in the muscle.
However, because a muscle fiber contracts along its entire length when
it is recruited (and will thereby require a corresponding increase in
capillary perfusion), it appears unlikely that a vasomotor response
would be confined to a single MVU.
ACKNOWLEDGEMENTS
We are grateful to Dr. A. J. Fuglevand for assistance with modeling of MVU alignment and for valuable discussion and critique of our work.
FOOTNOTES
Address for reprint requests: S. S. Segal, The John B. Pierce Laboratory, Yale Univ. School of Medicine, 290 Congress Ave., New Haven, CT 06519 (E-mail: sssegal{at}jbpierce.com).
Received 8 February 1996; accepted in final form 13 August 1996.
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