| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Deborah Research Institute and Department of Surgery, Deborah Heart and Lung Center, Browns Mills, New Jersey 08015
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Klabunde, Richard E., William A. Anderson, Marius Locke,
Sigrid E. Ianuzzo, and C. David Ianuzzo. Regional blood flows in
the goat latissimus dorsi muscle before and after chronic stimulation. J. Appl. Physiol. 81(6):
2365-2372, 1996.
Latissimus dorsi muscle (LDM) regional blood
flows were determined in anesthetized goats by using colored
microspheres under noncontracting and contracting conditions, either
before or after 8-10 wk of chronic muscle stimulation. Surgical
dissection of the LDM, leaving only the thoracodorsal artery to supply
the muscle, did not alter regional noncontracting blood flows but
significantly reduced the normal hyperemic response to muscle
contraction in muscle regions (posterior-medial) furthest from the
entrance of the thoracodorsal artery. Eight to 10 wk after acute muscle
dissection, posterior-medial hyperemic flows were restored. Chronic
stimulation of the LDM for 8-10 wk, in either dissected or
nondissected muscles, did not alter regional blood flows in
noncontracting muscle; however, it significantly reduced hyperemic
flows in all muscle regions, although capillary density was increased
and the muscle was transformed into a predominantly type I fiber type.
These results, coupled with data from previous experiments, suggest
that the muscle damage observed in the posterior-medial regions of the
LDM after surgical dissection and chronic stimulation may be related to
reduced hyperemic flow responses caused by surgical isolation of the
muscle.
cardiomyoplasty; skeletal muscle; muscle contraction; collateral
blood flow; ischemia; muscle transformation; capillary density; capillary-to-fiber ratio
INTRODUCTION THE LATISSIMUS DORSI MUSCLE (LDM) has been used in
human and experimental cardiomyoplasty to assist the failing heart (7, 8, 10, 22). Ordinarily, the LDM would be incapable of chronic repetitive contractions because it would undergo rapid fatigue. It is
possible, however, to transform the muscle from a type II to type I by
chronic stimulation over a period of several weeks, as shown in animal
(8, 16, 22, 25) and human (12) studies. This transformation enables the
LDM to become highly fatigue resistant and thereby be chronically
stimulated to contract long term (9). One potential limitation in using
the LDM in cardiomyoplasty is that it must be surgically separated from
its medial (spinal), anterior, posterior, and ventral attachments to
other tissues. This isolation procedure may result in reduced blood
flow capacity to the posterior-medial aspect of the muscle (26-28,
30) because of the removal of secondary vascular sources even though
the thoracodorsal artery (TDA), which enters the lateral aspect of the
muscle, is left intact. A major unanswered question is to what extent
the TDA and collateral vessels share in supplying the medial and
posterior aspects of the LDM. Surgical isolation of the pedicle
transplant, therefore, may result in a large zone of muscle ischemia
and eventual tissue necrosis. The region of the LDM most affected would
be the very region that is used to wrap the heart and provide the dynamic contractile assist in the cardiomyoplasty procedure. It is also
possible that regions within the posterial medial aspect of the muscle
may have normal resting blood flows; however, because the vasculature
may already be dilated by autoregulation, muscle contraction may not
result in a normal hyperemic response that is necessary to support
tissue metabolism during increased metabolic activity (26). This would
result in relative ischemia and tissue hypoxia during contraction and
possibly lead to diminished muscle performance in that region and
further exacerbate damage and necrosis.
The purpose of this study was to determine before and after 8-10
wk of chronic stimulation 1)
noncontracting blood flows to different regions of the LDM in the
anesthetized goat; 2) the hyperemic
response in different muscle regions during muscle contraction; 3) the effect of occlusion of the
TDA and ligation of secondary, posterior-medial blood supplies to the
LDM during rest and contraction; and
4) the effects of chronic
stimulation on capillary density and the number of capillaries per
muscle fiber in transformed and nontransformed muscle. The goat LDM was
used in this study because it has recently been found morphologically
and biochemically to most closely resemble the human LDM (18). This
experimental approach has been used because it provides necessary
information regarding blood flow deficits that result from surgery
associated with the cardiomyoplasty procedure and the possible role of
this ischemia in muscle degeneration (17).
METHODS All animals were treated humanely in accordance with
the "Principles of Laboratory Animal Care" formulated by the
National Society for Medical Research and the "Guide for the Care
and Use of Laboratory Animals" prepared by the Institute of
Laboratory Animal Resources and published by NIH [DHEW
Publication No. (NIH) 86-23, revised 1985, Office of Science and Health
Reports, DRR/NIH, Bethesda, MD 20892]. The protocol was approved
by the Animal Care Committee of the Deborah Research Institute.
Two separate studies, acute and chronic, were conducted. The acute
study involved anesthetizing goats and measuring regional LDM blood
flow at rest and during muscle contraction. The chronic study involved
two surgical procedures. The first procedure was conducted to ligate
the collateral vessels of the LDM and attach a nerve-cuff electrode for
subsequent chronic stimulation of the muscle. The second procedure,
which occurred 8-10 wk after the first, involved anesthetizing the
goat and measuring regional LDM blood flows at rest and during muscle
contraction. Histological data from the chronic study have been
previously published (17).
|
||||||||||||||||||||||||||||||||
Anatomically, region 1/2 was closest to the TDA (lateral muscle) and regions 7/8 and 9/10 (medial muscle) were closest to the entrance of secondary, distal vascular supply to the muscle, which was typically composed of two to three separate arterial-venous pairs entering the muscle in region 8. Chronic study. Ten castrated male Nubian goats (25-47 kg) were premedicated with ketamine (10 mg/kg im) and diazepam (0.5 mg/kg im) and anesthetized with isoflurane (1.5-2.0%; NarcoMed AVE-K, North American Dräger). The animals were intubated and mechanically ventilated at 400-ml tidal volume and 18 breaths/min. Body temperature and arterial blood gases were maintained as in the acute study. Sterile procedure was used throughout the operation. An incision was made that extended along the lateral and posterior borders of the LDM from the axillary fold to the costal margin of the 11th rib. In one group of goats (n = 5), the thoracodorsal neurovascular bundle was carefully dissected on the right side, a nerve-cuff electrode (model 4080, Medtronic) was placed around the thoracodorsal nerve (TDN), and the electrode was connected to an Itrel pulse generator (model 7421, Medtronic) located in a subcutaneous pocket. This muscle group was designated as nondissected and stimulated LDM (group S). The left LDM was surgically dissected from surrounding tissues with ligation of all collateral vessels, which consisted of one to three vessels located in the middle and distal aspect of the muscle, and the nerve-cuff electrode was placed around the TDN but was not connected to a pulse generator (group D, dissected only). In the second group of goats (n = 5), the left LDM was completely dissected from surrounding tissues with ligation of all collateral vessels and the anterior border of the LDM dissected free from the underlying musculature while the origin and insertion of the LDM were left intact. A nerve-cuff electrode was placed around the TDN and connected to a pulse generator (group DS, dissected and stimulated). The right LDM had a nerve cuff placed around the TDN but was not dissected or stimulated (group N). In all the dissected muscles, the TDA and TDN (i.e., the thoracodorsal neurovascular bundle), the aponeurosis origin, and the muscle insertion were left intact. During closure, the lateral and posterior borders of the LDM were carefully sutured to the underlying musculature by using nonabsorbable sutures (O-coated VICRYL) so as to attach the muscle precisely in its original anatomic location. After a 14-day recovery period, the pulse-generator program was activated with the following parameters: amplitude, 5 V; pulse width, 210 µs; burst frequency, 10 Hz for the first 2 wk of stimulation and 30 Hz thereafter; burst duration, on time of 190 ms and off time of 500 ms. After the chronic muscle stimulation period of 8-10 wk, the animals were anesthetized as before and muscle blood flows at rest and during stimulation were determined by using colored microspheres. The second procedure in the chronic study was very similar to the acute study. Briefly, the goat was anesthetized with isoflurane after premedication with ketamine, intubated, and placed in a ventilator, and a gastric tube was inserted. A catheter was positioned in the left ventricle via the carotid artery for microsphere injection, and a femoral artery was cannulated for the reference blood withdrawal and for obtaining blood samples for blood-gas measurements. There were two injections of microspheres during each experiment. The first injection (yellow microspheres) was conducted 30 min after the Itrel pulse generators were deactivated so that resting LDM blood flow could be obtained. The second injection (blue microspheres) occurred 5 min after initiation of muscle contraction by using the same stimulation parameters used during chronic stimulation. The procedures followed for the microsphere injections were identical to those used in the acute study. At the conclusion of the experiment, muscle samples were obtained from both LDMs in all 10 goats. The total muscle weights ranged between 69 and 164 g. Muscle weights relative to body weights were previously reported (17). Muscle samples (1.1-3.7 g) were obtained from three muscle regions for blood flow determinations (proximal, middle, and distal, relative to the muscle insertion onto the humerus). The proximal region corresponds to regions 1-4 (Fig. 1), the middle region to regions 5-8 (Fig. 1), and the distal regions to region 9/10 (Fig. 1). Microsphere processing. The reference blood samples and muscle biopsy samples were processed as follows for determination of blood flow. KOH (4 M) containing 0.05% Tween 80 was added to the tissue samples (previously trimmed of fat and weighed), and 16 M KOH were added to the blood (equal volumes of KOH to the blood and 7 ml of KOH to the tissue samples). The samples were digested at room temperature until digestion was complete. The digested tissue solution was heated to 72°C for 2 h and quickly vacuum filtered (10-µm pore size; 25-mm-diameter filter). Ethanol (70%) was used to wash the filtered spheres. The washed and dried spheres (with the filter paper) were then placed into a 1.5 ml Eppendorf tube to which 300 µl of N,N-dimethylformamide (DMF) were added to extract the dye. After vortexing and centrifugation (2,000 g), 100 µl of the DMF-dye solution were transferred to a spectrophotometer cuvette. The extracted dye was scanned on a spectrophotometer (model DU640, Beckman) at wavelengths between 350 and 820 nm. The absorption spectrum was saved as an ASCII file and transferred to a computer running the MISS program (Triton Technology). This program separates the individual components of the compound absorbance spectra, which has overlapping spectra of the different dyes. The reference samples, tissue samples, and standards spectra, along with tissue weights, were entered into the program for computation of blood flow. The sample blood flow values were entered into a spreadsheet and expressed as milliliters per minute per 100 g tissue weight. When only two microsphere colors were used, which did not have overlapping spectra (blue and yellow microspheres), the peak absorbance at the specified wavelength was entered into an Excel spreadsheet for computation of flow instead of using the MISS program. Capillary density determination. Capillaries were stained for alkaline phosphatase by using a modified procedure as described by Yang et al. (31). Statistical evaluation. The data were analyzed by one-way analysis of variance followed by the Dunnett's multiple-comparison test using InStat (Graphpad Software, San Diego, CA).
RESULTS
1 · 100 g1 (Fig.
2). Occlusion of the TDA did not
significantly alter whole muscle blood flow (2.7 ± 0.2 ml · min1 · 100 g1). Ligation of the
posterior-medial blood supplies caused whole muscle blood flow to
increase to 7.7 ± 0.5 ml · min1 · 100 g1
(P < 0.05 relative to control
resting flow group). This increase in blood flow may have been due to
acute surgical trauma or to sympathetic denervation. Therefore, removal
of either the lateral (TDA) or posterior-medial vascular supplies did
not reduce whole muscle resting blood flow. Furthermore, resting blood
flows within the five muscle regions were not significantly different
in resting control muscles, TDA-occluded muscles, or
posterior-medial-occluded muscles (Fig. 3).
This indicated that adequate collaterals existed to maintain normal
resting flows despite complete occlusion of either the TDA or
posterior-medial vascular supplies. Muscle having the posterior-medial
vascular supply ligated, however, had significantly higher resting
flows (2- to 4-fold) in all regions compared with the control and
TDA-occluded muscles (Fig. 3). The higher resting flows in this group
resulted from all the regions in one muscle having particularly high
resting flows (~15
ml · min1 · 100 g1).
Muscle contraction induced by electrical stimulation of the nerve caused a large hyperemic response measured 3 min after contraction was initiated. In control muscles having an intact vascular supply, muscle contraction for 3 min caused whole muscle blood flow to increase to 64.5 ± 0.9 ml · min
1 · 100 g1 (Fig. 2). Occlusion of
the TDA significantly reduced the whole muscle hyperemia to 26.3 ± 8.7 ml · min1 · 100 g1. Therefore, the
posterior-medial vasculature supplied 41% of the total muscle blood
flow during contraction. Ligation of the posterior-medial vascular
supply limited the increase in blood flow during contraction to 43.0 ± 10.3 ml · min1 · 100 g1. Therefore, the TDA
supplied 67% of the total muscle blood flow during contraction under
these experimental conditions. Removal of either the TDA or
posterior-medial vascular supply to the LDM significantly diminished by
30-60% the increase in blood flow associated with muscle
contraction. This indicates that both vascular supplies (TDA and
posterior-medial) are required to achieve normal hyperemic responses to
contraction, as would need to occur with cardiomyoplasty.
The effects of vascular occlusion on active hyperemia were even more
pronounced when the five regional blood flows were compared. Occlusion
of the TDA during muscle contraction severely compromised active
hyperemia in regions 1/2 (8.2 ± 3.1 ml · min1 · 100 g1),
3/4 (8.3 ± 3.4 ml · min1 · 100 g1), and
5/6 (21.0 ± 6.9 ml · min1 · 100 g1), which are in the
lateral and middle regions of the muscle near the entrance of the TDA
into the muscle (Fig. 4). These muscle regions when left intact had hyperemic flows >60
ml · min1 · 100 g1. These reduced hyperemic
flows, however, were still above control resting flow, which averaged
~2
ml · min1 · 100 g1 in these regions (Fig.
3). In contrast, active hyperemia in the posterior-medial regions
(7/8 and
9/10) was maintained during TDA
occlusion.
Removal of the posterior-medial vascular supply resulted in greatly diminished active hyperemia in the distal regions of the muscle. The hyperemic flows were 15.5 ± 2.4 and 23.3 ± 5.1 ml · min
1 · 100 g1 in
regions 7/8 and
9/10, respectively. These reduced
hyperemic flows, nevertheless, were above control resting flows in
these same regions (Fig. 3). The flow responses in the lateral regions (1/2 and
3/4) and middle muscle regions
(5/6) were essentially normal
(50-70
ml · min1 · 100 g1). Therefore, removal
of the posterior-medial vascular supply to the LDM during surgical
dissection, while not affecting resting flow, prevents normal hyperemic
responses of the medial muscle regions during muscle contraction.
Chronic study.
Resting blood flow in control muscles (group
N) was 6.5 ± 0.7 ml · min1 · 100 g1 (Fig.
5) and was the same in the proximal,
middle, and distal muscle regions (Table
2). LDM resting blood flows
8-10 wk after surgical dissection (group
D), dissection plus chronic stimulation (group DS), or chronic stimulation without
dissection (group S) were not different among
the groups (Fig. 5). Furthermore, there were no regional differences in
resting flows among the groups (Table 2). Therefore, none of the
interventions (dissection, chronic stimulation, or both combined)
altered resting blood flows.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 · 100 g1 (Fig. 5). The magnitude
of active hyperemia was similar in the three muscle regions (Table 2).
Surgical dissection alone (group D) did not
significantly reduce total muscle blood flow or regional flows during
contraction, although there was a tendency for the active hyperemia to
be reduced in the middle and distal muscle regions. When the surgical
dissection was combined with chronic stimulation (group
DS), there was an overall reduction in muscle blood
flow during contraction, with the reduction being similar in all three
muscle regions. In these muscles, contraction resulted in only a
threefold increase in flow. Chronic stimulation alone, without surgical
dissection (group S), also resulted in
reduced hyperemic flows.
In control muscles, the capillary density was 308 ± 28/mm2 and the capillary-to-fiber
ratio was 1.01 ± 0.04 capillaries/fiber (Fig.
6). Muscle dissection alone (group
D) did not alter capillary numbers; however, chronic
stimulation with or without dissection (groups
DS and S,
respectively) resulted in a significant increase in the capillary
number expressed either as capillary-to-fiber ratio or capillaries per
square millimeter, both of which increased ~60% (Fig. 6). There were
no differences in capillary numbers among the proximal, middle, and
distal regions of the muscle in any treatment group. Therefore, chronic
stimulation for 8-10 wk increased the total number of capillaries
throughout the LDM and the number of capillaries around each muscle
fiber. Furthermore, this increase in capillary density was not altered
by surgical dissection and removal of posterior-medial vascular
supplies to the LDM.
DISCUSSION
A major concern in using the LDM in cardiomyoplasty is that the surgical dissection of the muscle results in the ligation of several arterial sources for perfusing the LDM, particularly the posterior-medial regions of the muscle (26-28, 30). If ischemic regions do not have blood flow restored through angiogenesis or collateralization, then necrotic changes will diminish the ability of those muscle regions to contract when wrapped around the heart. We determined that acute surgical dissection of the muscle, which included disruption of all vascular supply to the muscle except for that derived from the TDA, did not reduce blood flow in any muscle regions when the muscle was at rest. Therefore, adequate interconnections (collaterals) exist between the TDA and posterior-medial arterial supplies to ensure normal perfusion (as determined by the microsphere technique) when the secondary vascular supplies are removed. It is important to emphasize, however, that "resting" flow as defined in this study is the flow value found in noncontracting muscle of anesthetized goats and, therefore, may be significantly lower than "resting" flow found in the conscious animal (2, 20).
Although resting blood flows were not reduced by acute surgical dissection, the hyperemic response during muscle contraction was greatly diminished, particularly in the medial portions of the muscle that are used to wrap the heart in the cardiomyoplasty procedure. This could be of critical significance to the preservation of the dissected muscle because resting flow requirements are higher in the conscious animal (20, 21). Furthermore, normal postural and locomotory activities of the goat will elicit hyperemic responses that may not be adequately met in the dissected muscle until collateralization occurs. When blood flows were evaluated 8-10 wk after surgical dissection, resting blood flows were still normal in the three muscle regions, and unlike the findings in the acute study, the active hyeremic response to muscular contraction was not significantly impaired. This suggests that angiogenesis or collateralization occurs over the 8- to 10-wk period, which restores much of the acute loss of the hyperemic response resulting from muscle contraction.
Cardiomyoplasty has been used successfully in human patients as well as
in animal experiments (7, 8, 10, 22). To use skeletal muscle to provide
mechanical assistance to the failing heart, it is necessary to use a
muscle that is resistant to fatigue during chronic repetitive
stimulation. The muscle needs to be slow twitch (type I), highly
oxidative, and accessible for wrapping around the heart. There are no
muscles near to the heart (except for the diaphragm and pectoralis
major) that can be used for this purpose unless they are first
transformed from a mixture of type I and II fiber types to type I. It
has been shown that the LDM is well suited for this use and with
chronic stimulation can be transformed into a highly fatigue-resistant
type I muscle (8, 9, 12, 16, 17, 22, 25). It has been documented that the LDM exhibits muscle damage and necrosis in the very regions that
are used to wrap the heart (12, 17, 22). This damage can result from
surgical trauma, ligation of arterial supplies to the muscle,
mechanical obstruction of the blood flow as the muscle enters the
thorax, chronic stimulation and contraction of the LDM, change in
muscle length and/or tension, or a combination of any or all of these
factors. The ischemic-injury hypothesis is quite tenable
because the surgical isolation and translocation of the muscle require
ligating several arterial vessels that supply the muscle, particularly
the posterior-medial regions. Mannion et al. (26) and Isoda et al. (19)
found by using the dog LDM that ligation of these vessels reduced
resting flow and active hyperemia, particularly within the medial
regions of the muscle. The technique used by Isoda et al. for measuring
regional blood flows (He-Ne laser blood flowmeter), however, gave
questionable results because, although the resting blood flow values
were normal, the increases in regional blood flows during contraction
were only 1-2
ml · min1 · 100 g1. Total muscle flows
measured at the TDA increased by >15
ml · min1 · 100 g1 during contraction. This
lack of agreement between regional flows and total flows when expressed
per the same unit tissue weight suggests that the regional flow
measurement technique was not accurately measuring blood flow. Mannion
et al. (26) used radiolabeled microspheres and clearly showed
reductions in both resting and hyperemic flows in the medial regions of
the dog LDM. Our study has shown that ligation of these vessels does
not reduce resting blood flow to any region of the muscle, either
acutely or 8-10 wk after ligation. Therefore, the TDA is able to
supply all of the resting blood flow needs of the muscle, at least in
the anesthetized goat.
We found that the resting blood flow averaged ~3-6
ml · min1 · 100 g1 throughout the muscle.
These resting flow values are in the range of those observed in resting
skeletal muscle of other species when anesthetized (5, 11, 14, 15, 19,
21, 23). Because the oxygen requirements of resting skeletal muscle are low (5, 11, 14, 15), and oxygen extraction is low, these flows are
sufficient to prevent tissue hypoxia in noncontracting muscle. One
caveat to this is that our microsphere technique for assessing blood
flow used tissue samples of 1-3 g in weight, and flow
heterogeneity within the sample cannot be assessed. While the average
blood flow within these muscle samples was 3-6
ml · min1 · 100 g1, there may have been
regions within the sample that had subnormal flows. Some muscle fibers
may have been ischemic, which would lead to damage (17), while other
fibers may have been supplied with elevated blood flow under resting
conditions. Experiments need to be conducted to address the issue of
flow heterogeneity after surgical dissection. This could be done by
quantifying the number of functional (perfused) capillaries.
Although the acutely dissected LDM was not ischemic at rest (as determined within the limits of our technique), we found that blood flow during contraction was significantly compromised in the posterior-medial regions of the muscle. Ordinarily, when skeletal muscle contracts, vascular resistance falls and blood flow increases (active hyperemia) (5, 11, 14). A tight coupling normally exists between tissue oxygen consumption and blood flow in contracting muscle to maintain adequate oxygen supply to the tissue during contraction (4, 11). The acutely dissected LDM was unable to increase blood flow during contraction to the same degree as was nondissected muscle because its posterior-medial arterial supply was removed. Resting flow in the posterior-medial regions was normal probably because autoregulatory responses, and perhaps opening of preexisting collaterals, reduced vascular resistance within those regions to maintain flow. This fall in resistance, however, would diminish the vasodilatory capacity of these regions of the LDM during contraction, resulting in a reduction in the magnitude of active hyperemia. If the muscle oxygen consumption remained the same during contraction in dissected and nondissected muscles, then the reduced active hyperemia in the posterior-medial regions would lead to an insufficient oxygen supply and tissue hypoxia during contraction. Reduced hyperemic capacity in the dissected muscle could also result in inadequate blood flow during normal postural and locomotory activities where the blood flows are considerably higher than those observed in muscles from anesthetized animals (2, 20). Without adequate oxygen delivery, muscle contractile performance will be impaired and degenerative changes might occur. However, 3 mo after surgical dissection, the active hyperemic response was not significantly diminished, indicating that the hyperemic response, which was severely reduced after acute dissection, was restored. This restoration of hyperemic response (in nontransformed muscles) may have been due to opening of collaterals or formation of new collaterals by angiogenesis. Mannion et al. (26) observed a similar restoration of hyperemic flow 3 wk after vessel ligation in the dog LDM.
The medial regions of the goat LDM have been found to undergo degenerative changes 8-10 wk after surgical dissection (17). The present study suggests that this is probably not due to altered resting blood flow, unless there was flow heterogeneity within the samples. Because the degenerative changes were found predominantly in the distal (medial) regions of the LDM, this suggests that the degeneration was somehow associated with the removal of the secondary, distal vascular supply to the muscle. Although resting flow was not compromised either acutely or chronically, the hyperemic response to contraction was compromised, at least initially after the surgical dissection. Perhaps this initial reduction in flow capacity rendered the distal LDM regions hypoxic when the muscle contracted during normal postural and locomotory activities during the 8- to 10-wk postsurgical period, and this precipitated the degenerative changes in the muscle. Distal degeneration of the muscle (17) would also explain the tendency for the distal hyperemic response to be lower 8-10 wk postsurgery.
Chronic stimulation and transformation of the LDM in the absence or presence of surgical dissection resulted in decreased hyperemic blood flows at a given frequency of muscle contraction. Chronic stimulation alone does not cause significant muscle damage (17); therefore, damage cannot be the cause of the reduced functional hyperemia after chronic stimulation. The most likely explanation is that chronic stimulation transforms the LDM from a type II to a type I muscle (8, 9, 12, 16, 17, 22, 25). By the end of the 8- to 10-wk period of chronic stimulation, the type I fiber percent increased from ~35 to 95% (varied among muscle regions) (17). Type I fibers generate less force during contraction and use ATP more efficiently than do type II fibers (3) and therefore would consume less oxygen, thereby requiring a smaller increase in blood flow to supply oxygen to the tissue. In a study by Acker et al. (1), dog LDM transformed by electrical stimulation in a manner similar to that in our study had significantly reduced hyperemic flows for a given tension-time index, suggesting increased efficiency. Mannion et al. (26) also noted decreased hyperemic responses in electrically tranformed dog LDM when contracting at different frequencies. On the other hand, it should be noted that muscles transformed by exercise training rather than electrical stimulation generally show increased hyperemic responses at a given frequency of tetanic trains of stimulation in situ (24).
It is well established that highly oxidative muscle fibers have more capillaries than do low-oxidative fibers (13, 29) and that chronic electrical stimulation induces angiogenesis (6). The chronic burst-stimulation protocol used in this study induced a 64% increase in capillary-to-fiber ratio in the nondissected and stimulated LDM, which compares favorably with the 75% increase in capillary-to-fiber ratio in rabbit fast-twitch muscle that was stimulated for 28 days by using a continuous 10-Hz frequency (6). Capillary-to-fiber ratios have been shown to have a high correlation with the oxidative capacity of muscle (13). In this study, the nearly twofold increase in capillary-to-fiber ratio was associated with an approximate twofold increase in oxidative capacity (17). The capillary density increased from 308 ± 28 capillaries/mm2 in control muscles to 542 ± 28 capillaries/mm2 in chronically stimulated muscles (76% increase). This percent increase is slightly greater than the percent increase in capillary-to-fiber ratio because of the smaller fiber diameter in the transformed muscle (17).
In summary, we have shown that surgical dissection of the LDM in anesthetized goats reduces acutely the hyperemic response to muscle contraction in the posterior-medial regions of the muscle without affecting resting blood flow. This reduction in hyperemic flow may have deleterious consequences (e.g., enhance muscle damage) when an electrical stimulation protocol is imposed on the muscle that results in a large increase in oxygen demand that cannot be met by the blood supply. Furthermore, hyperemic responses to normal postural and locomotory activity might also be impaired in the dissected muscle, which will further enhance muscle damage. The hyperemic response is restored to a large extent 8-10 wk later; however, the posterior-medial regions of the muscle are already damaged at this time (17). Transformation of the LDM from a type II to a type I muscle by using chronic stimulation, in surgically dissected or intact muscles, resulted in a greatly diminished active hyperemic response throughout the LDM and is probably a consequence of the change in fiber type to a more efficient oxidative type I fiber composition within the LDM.
ACKNOWLEDGEMENTS
We thank Connie Daloisio and Pam Straeter for excellent technical assistance in these experiments.
FOOTNOTES
Address for reprint requests: R. E. Klabunde, Deborah Research Institute, Browns Mills, NJ 08015.
Received 16 January 1996; accepted in final form 18 July 1996.
REFERENCES
| 1. | Acker, M., R. L. Hammond, J. McCullum, M. Velchik, D. Gale, and L. W. Stephenson. Oxygen consumption of chronically stimulated skeletal muscle. J. Thorac. Cardiovasc. Surg. 94: 702-709, 1987. |
| 2. | Armstrong, R. B., M. D. Delp, E. F. Goljan, and M. H. Laughlin. Progressive elevations in muscle blood flow during prolonged exercise in swine. J. Appl. Physiol. 63: 285-291, 1987. |
| 3. | Awan, M. Z., and G. Goldspink. Energy utilization by mammalian fast and slow muscle in doing external work. Biochim. Biophys. Acta 216: 229-230, 1970. |
| 4. | Bockman, E. L. Blood flow and oxygen consumption in active soleus and gracilis muscle in cats. Am. J. Physiol. 244 (Heart Circ. Physiol. 13): H546-H551, 1983. |
| 5. | Bockman, E. L., J. E. McKenzie, and J. L. Ferguson. Resting blood flow and oxygen consumption in soleus and gracilis muscles of cats. Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H516-H524, 1980. |
| 6. | Brown, M. D., M. A. Cotter, O. Hudlicka, and G. Vrbova. The effects of different patterns of muscle activity on capillary density, mechanical properties and structure of slow and fast rabbit muscles. Pfluegers Arch. 361: 241-250, 1976. |
| 7. | Carpentier, A., J. C. Chachques, C. Acar, J. Relland, S. Mihaileanu, D. Bensasson, J. P. Kieffer, P. Guibourt, D. Tournay, I. Roussin, and P. A. Grandjean. Dynamic cardiomyoplasty at seven years. J. Thorac. Cardiovasc. Surg. 106: 42-54, 1993. |
| 8. | Chachques, J. C., P. A. Grandjean, K. Schwartz, S. Mihaileanu, M. Fardeau, B. Swynghedauw, F. Fontaliran, N. Romero, C. Wisnewsky, P. Perier, S. Chauvaud, I. Bourgeois, and A. Carpentier. Effect of latissimus dorsi dynamic cardiomyoplasty on ventricular function. Circulation 78, Suppl. III: III-203-III-216, 1988. |
| 9. | Chiu, R. C.-J., G. Kochamba, G. Walsh, M. Dewar, C. Desrosiers, T. Dionisopoulos, P. Brady, and C. D. Ianuzzo. Biochemical and functional correlates of myocardium-like transformed skeletal muscle as a power source for cardiac assist devices. J. Cardiovasc. Surg. 4: 171-179, 1989. |
| 10. | Cho, P. W., H. R. Levin, W. E. Curtis, J. E. Tsitlik, J. M. DiNatale, D. A. Kass, T. J. Gardner, R. W. Kunel, and M. A. Acker. Pressure-volume analysis of changes in cardiac function in chronic cardiomyoplasty. Ann. Thorac. Surg. 56: 38-45, 1993. |
| 11. | Folkow, B., and H. D. Halicka. A comparison between `red' and `white' muscle with respect to blood supply, capillary surface area and oxygen uptake during rest and exercise. Microvasc. Res. 1: 1-14, 1968. |
| 12. | Grimby, G., A. Nordwall, B. Hulten, and K. G. Henriksson. Changes in histochemical profile of muscle after long-term electrical stimulation in patients with idiopathic scoliosis. Scand. J. Rehabil. Med. 17: 191-196, 1985. |
| 13. | Hoppeler, H., and S. R. Kayar. Capillarity and oxidative capacity of muscles. News Physiol. Sci. 3: 113-116, 1988. |
| 14. | Hudlicka, O. Uptake of substrates in isolated contracting slow and fast muscles in situ in relation to fatigue. In: Muscle Metabolism During Exercise, edited by B. Pernow, and B. Saltin. New York: Plenum, 1971, p. 215-223. |
| 15. | Hudlicka, O., and S. Price. The role of blood flow and/or muscle hypoxia in capillary growth in chronically stimulated fast muscles. Eur. J. Physiol. Occup. Physiol. 417: 67-72, 1990. |
| 16. | Ianuzzo, C. D., N. Hamilton, P. J. O'Brien, C. Desrosiers, and R. Chiu. Biochemical transformation of canine skeletal muscle for use in cardiac-assist devices. J. Appl. Physiol. 68: 1481-1485, 1990. |
| 17. | Ianuzzo, C. D., S. E. Ianuzzo, N. E. Carson, M. Feild, M. Locke, J. Gu, W. A. Anderson, and R. E. Klabunde. Cardiomyoplasty: degeneration of the assisting skeletal muscle. J. Appl. Physiol. 80: 1205-1213, 1996. |
| 18. | Ianuzzo, C. D., S. E. Ianuzzo, N. Chalfoun, M. Feild, M. Locke, J. Fernandez, and R. C.-J. Chiu. Cardiomyoplasty: comparison of latissimus dorsi muscles of three large mammals with that of human. J. Cardiovasc. Surg. 11: 30-36, 1996. |
| 19. | Isoda, S., Y. Yano, J. Yasuyuki, H. L. Walters, J. Kondo, and A. Matsumoto. Influence of a delay on latissimus dorsi muscle flap blood flow. Ann. Thorac. Surg. 59: 632-638, 1995. |
| 20. | Laughlin, M. H., and R. B. Armstrong. Muscle blood flow during locomotory exercise. Exercise Sport Sci. Rev. 13: 95-139, 1985. |
| 21. | Laughlin, M. H., R. B. Armstrong, J. White, and K. Rouk. A method for using microspheres to measure muscle blood flow in exercising rats. J. Appl. Physiol. 52: 1629-1635, 1982. |
| 22. | Lucas, C. M. H. B., F. H. Van der Veen, E. C. Cheriex, R. Lorusso, M. Havenith, O. C. K. M. Penn, and H. J. J. Wellens. Long-term follow-up (12 to 35 weeks) after dynamic cardiomyoplasty. J. Am. Coll. Cardiol. 22: 758-767, 1993. |
| 23. | Mackie, B. G., and R. L. Terjung. Blood flow to different skeletal muscle fiber types during contraction. Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H265-H275, 1983. |
| 24. | Mackie, B. G., and R. L. Terjung. Influence of training on blood flow to different skeletal muscle fiber types. J. Appl. Physiol. 55: 1072-1078, 1983. |
| 25. | Mannion, J. D., T. Bitto, R. L. Hammond, N. A. Rubinstein, and L. W. Stephenson. Histochemical and fatigue characteristics of conditioned canine latissimus dorsi muscle. Circ. Res. 58: 298-304, 1986. |
| 26. | Mannion, J. D., M. Velchik, R. Hammond, A. Alavi, T. Mackler, S. Duckett, M. Staum, S. Hurwitz, W. Brown, and L. W. Stephenson. Effects of collateral blood vessel ligation and electrical conditioning on blood flow in dog latissimus dorsi muscle. J. Surg. Res. 47: 332-340, 1989. |
| 27. | Mathes, S. J., and F. Nahai. Classification of the vascular anatomy of muscles: experimental and clinical correlation. Plast. Reconstr. Surg. 67: 177-187, 1981. |
| 28. | Radermecker, M. A., M. Triffaux, J. Fissette, and R. Limet. Anatomical bases of medical, radiological or surgical techniques. Anatomical rationale for use of the latissimus dorsi flap during the cardiomyoplasty operation. Surg. Radiol. Anat. 14: 5-10, 1992. |
| 29. | Reis, D. J., and G. F. Wooten. The relationship of blood flow to myoglobin, capillary density, and twitch characteristics in red and white skeletal muscle in cat. J. Physiol. Lond. 210: 121-135, 1970. |
| 30. | Tobin, G. R., M. Schusterman, G. H. Peterson, G. Nichols, and K. I. Bland. The intramuscular neurovascular anatomy of the latissimus dorsi muscle: the basis of splitting the flap. Plast. Reconstr. Surg. 67: 637-641, 1981. |
| 31. | Yang, H. T., R. W. Ogilvie, and R. L. Terjung. Peripheral adaptations in trained aged rats with femoral artery stenosis. Circ. Res. 74: 235-243, 1994. |
This article has been cited by other articles:
|
|
 |
|
  D. Bouamrirene, J.-P. Micallef, P. Rouanet, and F. Bacou Electrical Stimulation-Induced Changes in Double-Wrapped Muscles for Dynamic Graciloplasty Arch Surg, October 1, 2000; 135(10): 1161 - 1167. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
