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Cardiothoracic Surgery Research, Allegheny University of the Health Sciences, Department of Surgery, Allegheny University Hospitals, Allegheny General, Pittsburgh, Pennsylvania 15212
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Skeletal muscle is highly adaptable in that its metabolic and contractile characteristics are largely regulated by its pattern of use. It is known that muscle phenotype can be manipulated via chronic electrical stimulation to enhance fatigue resistance at the expense of contractile power. Type 2A fibers are fatigue resistant, powerful, and considered most desirable for cardiac assist purposes. We have found that 12-wk of intermittent-burst stimulation produces a high percentage of 2A fibers and increases fatigue resistance and power in rabbit latissimus dorsi muscle. Fixed-load endurance tests were used to quantify fatigue resistance among normal and trained muscle groups. Control muscles were found to fatigue completely within 10-20 min. Muscles stimulated continuously for 6 wk retained 35% (71.5 ± 19.5 g · cm) of their initial stroke work at 40 min. Muscles stimulated 12 h/day for 12 wk had the highest initial stroke work (449.7 ± 92.4 g · cm) and the highest remaining stroke work (234.7 ± 50.1 g · cm) at 40 min. Results suggest that employing regular resting periods during conditioning preserves strength in fatigue-resistant muscle.
skeletal muscle; burst stimulation; muscle power; rest periods; fiber transformation
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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FUNDAMENTAL ISSUES concerning the feasibility of muscle-powered circulatory support remain to be fully explored, including questions surrounding the endurance and steady-state work capacity of trained skeletal muscle (1, 16). It is well-established that muscles fully transformed by continuous electrical stimulation (100% type 1 fibers) display significant losses in power (7, 14, 17, 20). The exact mechanism for this is not known, but it is generally attributed to the loss of type 2 fibers and the reduction in muscle mass that results from the transformation process (8, 12, 19). Several studies have demonstrated that voluntary exercise training in humans does not increase type 1 fiber content, but rather produces a shift from type 2X or 2B to type 2A muscle fibers (2, 3, 6). On the basis of these results, we hypothesize that the introduction of rest periods into the training regimen will result in a more powerful fatigue-resistant muscle by maintaining a larger population of type 2 oxidative fibers and/or preserving muscle mass. The purpose of the present study is to test the hypothesis that intermittent stimulation of the latissimus dorsi (LD) muscle will improve muscle function and limit the conversion of type 2 fibers to type 1 fibers for an extended period.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Animals and Animal Care
New Zealand White rabbits (2-4 kg, female) were used in these experiments. All animals received humane care in compliance 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 [DHEW Publication No. (NIH) 85-23, Revised 1985, Office of Science and Health Reports, DRR/NIH, Bethesda, MD 20205].Surgical Procedure
Sterile techniques were used for all operative procedures. Medtronic Itrel3 neuromuscular stimulators (model 7425) and custom paraneural leads (US Patent no. 5,158,097) were used to condition the muscles. Animals were preanesthetized with xylazine and ketamine, intubated, and placed on a ventilator. Anesthesia was maintained with a mixture of 50% oxygen, 48-49% nitrous oxide, and 1-2% isoflurane. Acepromazine and atropine were given to control secretions. Electrocardiogram monitoring was performed in each case. A lateral incision was made in the skin and subcutaneous muscle along the left hemithorax. Hemostasis was achieved without the use of electrocautery. The proximal medial border of the LD was dissected free from adjacent structures and elevated from the chest wall by gentle retraction. The thoracodorsal nerve branch entering the insertion of the LD was identified. The cathode of the paraneural electrode was sutured to the muscle fibers adjacent to the neural bundle. The LD was secured in its native location in preparation for in situ stimulation. The stimulator was tunneled into the abdominal subcutaneous tissue, and the incision was closed in the standard fashion. Antibiotics were given preoperatively and for three days postoperatively.Stimulation Parameters
The left and right LD from each animal were chosen for stimulation and control studies, respectively. Muscles were conditioned using the following stimulation parameters.Continuous-burst stimulation. Continuous-burst stimulation was at 2.0 V, 250-ms burst duration, 880-ms interburst interval, 210-µs pulse width with a 10-Hz (week 1), 16 Hz, (week 2), 20 Hz (week 3), and 25 Hz (week 4 and above) burst frequency for 24 h/day.
Intermittent-burst stimulation. Intermittent-burst stimulation was at 2.0 V, 250-ms burst duration, 880-ms interburst interval, 210 µs pulse width with a 10-Hz (week 1), 16 Hz (week 2), 20 Hz (week 3), and 25 Hz (week 4 and above) burst frequency for 12 h/day.
Continuous single-pulse stimulation. Continuous single-pulse stimulation was at 2.0 V, 1.05 pulses/s, 210-µs pulse width for 24 h/day.
Muscle Mechanics Testing
On completion of the stimulation protocol, the animals received premedication similar to that used for surgery, without endotracheal intubation. Muscle peak isometric force was measured over five contractions with the same stimulation pattern used for muscle conditioning (because preserving a given fiber type distribution over the long term requires that skeletal muscle be activated with the same pulse pattern used during training). Muscle contractile energetics and fatigue resistance were determined under the same stimulation conditions from 40 min to 8 h.Each function study employed a custom skeletal muscle ergometer designed to impose isometric or isotonic loading conditions on the muscle. A fixed-weight pulley system was used to produce near isotonic loads on the muscle, allowing the LD to shorten during contraction and, hence, generate external work. This technique was chosen as a simple means to simulate chronic work conditions and quantify the degree to which normal and conditioned muscles maintain their initial level of work production. The terminal load comprises a stack of weights (145 g total mass) attached to the LD muscle by a thin cord traversing a stationary pulley. (Note: this load level was established through prior experience as the largest weight readily lifted by most fully conditioned rabbit LD muscles.) Motion was measured with a pair of sonomicrometry crystals (sonomicrometer model 120, Triton Technology) mounted beneath the weights on telescoping, fluid-filled pipettes. Forces were measured through a strain gauge (model LCL-816G, Omega Engineering) mounted between the load and the muscle. To ensure that this load was transmitted directly to the LD muscle, the ergometer was secured to the LD muscle origin via Teflon felt sutured to the cable. Each animal was held in position to minimize body displacement in response to muscle contraction against the load.
The rationale for testing muscle performance in this manner centers on the need to measure peak work production under stimulation conditions compatible with direct cardiac assistance. Brief cardiac work cycles preclude the use of prolonged LD contractions for purposes of coordinated circulatory support, and thus practical LD activation times are limited to ~250 ms. Because full muscle shortening cannot be completed in this short time frame (due to the magnitude of the terminal load used in these experiments), load displacement is determined solely by muscle strength and speed, and, hence, initial stroke work levels are near maximum for all muscles tested. Because muscle-powered circulatory assist relies most heavily on chronic work capacity, this method of durability testing was considered most appropriate.
Experimental Design
Protocol I. This experiment was designed to investigate the effects of long-term continuous-burst stimulation on LD muscle function and morphology. Eight rabbits were assigned to one of two groups (6-wk and 12-wk stimulation). The entire left LD muscle from each animal was stimulated, and the right LD served as a paired control. Peak isometric force was measured over five contractions with the same stimulation pattern used for muscle conditioning. Contractile energetics and fatigue resistance were determined under the same stimulation conditions for 40 min. Immunohistochemical analysis of the muscle was used to determine muscle fiber types and to measure fiber cross-sectional area (CSA).Protocol II. This experiment was designed to test the effects of continuous low-frequency stimulation on muscle fiber transformation. Continuous single-pulse stimulation delivered at 10 pulses/s is known to induce complete conversion of skeletal muscle fibers to the type 1 phenotype. It was hypothesized that single-pulse stimulation delivered at lower frequencies would reduce the degree of phenotype transformation and yield a stable population of powerful type 2A muscle fibers. Six rabbits were divided into two groups (6 wk and 12 wk) with continuous single-pulse stimulation. Immunohistochemical analysis of the muscle was used to identify muscle fiber types and measure fiber CSA.
Protocol III. This experiment was designed to determine the effect of long-term intermittent-burst stimulation on muscle fiber phenotype expression, contractile function, fiber CSA, and metabolism. Ten rabbits were randomly assigned to two groups of five each: 1) 6 wk of continuous-burst stimulation (6-wk continuous, 24 h/day) and 2) 12 wk of intermittent-burst stimulation (12-wk intermittent, 12 h/day). Burst-stimulation parameters were identical to protocol I. Because LD muscles after intermittent-burst stimulation training were so powerful and resistant to fatigue, muscle fatigue resistance was determined beyond 40 min (up to 8 h). Immunohistochemical analysis of the muscle was used for muscle fiber typing and CSA measurement. Electrophoretic analysis was used to identify the various myosin heavy chains (MHC) present. Biochemical analysis techniques were used to measure muscle metabolic enzymes.
Analytic Procedures
Immunohistochemical analysis for muscle fiber types and CSA. Fiber type identification was performed as described by Schiaffino et al. (18). Cryosections of muscle samples were fixed with cold AFA fixative (50 ml of 37-40% formaldehyde + 370 ml 95% ethanol + 25 ml glacial acetic acid) for 5 min. Slides were then washed two times with 1× PBS. A 5% dry milk block in 1× PBS was then applied to the slides and they were incubated in a humid chamber at room temperature for 1 h. Excess milk block was then removed, the primary antibodies to the myosin heavy chains, type I (BA-D5), type 2A (SC-71), type 2B (BF-F3), and type 2X (BF-35), were added to the appropriate sections, and the slides were incubated at 4°C overnight. The slides were then washed two times with 1× PBS, and a secondary antibody (Biogenex-biotinylated anti-mouse IgG) was applied to the sections that were incubated in a humid chamber at room temperature for 30 min. Slides were washed two times as above, and a streptavidin alkaline phosphatase conjugate (Biogenex) was added. The slides were incubated for another 30 min at room temperature. The streptavidin conjugate was removed by washing (as in prior steps), and the substrate, comprising a naphthol buffer containing Fast red with 125 mM levamisole (to block endogenous phosphatase), was added. Slides were observed under the microscope and the development was stopped when the desired degree of staining was achieved. Muscle cross sections were divided into four or five evenly spaced regions, depending on the size of the sample. Representative fascicles with fibers cut perpendicular to their long axes were measured with the use of an OPTIMAS 6 image processing system. This system consists of a microscope with an attached camera coupled to a Compaq personal computer, optical mouse, and an image processor.Analysis of MHC. Myosin extraction was
performed as described by La Framboise et al. (10). Muscles were minced
finely, and myosin was extracted on ice for 40 min in four volumes of
buffer (pH 6.5) as previously described by Butler-Browne and Whalen
(5). The extracted myosin was diluted in nine volumes of 1 mM
EDTA and 0.1% 2-mercaptoethanol (vol/vol) and cooled at
4°C overnight to allow precipitation of myosin filaments. The
filament solution was centrifuged at 13,000 g for 30 min at 4°C to form a
pellet, which was then dissolved in a myosin sample buffer containing 0.5 M NaCl and 10 mM
NaH2PO4.
It was then diluted 1:200 in an SDS sample buffer [6.25 mM
Tris · HCl, 2% (wt/vol) SDS, 10% glycerol, 5%
(vol/vol) 2-mercaptoethanol, and 0.001% (wt/vol) bromphenol blue at pH
6.8]. Before the bromphenol blue was added to the sample buffer,
a small amount of the myosin extract was removed, and a total protein
determination was assayed by the Bradford method (4). The samples were
boiled for 2 min and stored in aliquot at 
80°C. The
separation of MHC isoforms was done by using SDS-PAGE as described by
Talmadge et al. (18a). The separating gels were composed of 30%
glycerol, 8% acrylamide-bis (50:1), 70 mM Tris (pH 6.8), 4 mM EDTA,
and 0.4% SDS. Polymerization of the gels was initiated with 0.05%
N,N,N',N'-tetramethylethylenediamine and 0.1% ammonium persulfate. The gels were run on a Hoefer SE600 large gel electrophoretic unit using a running buffer in the upper chamber consisting of 0.1 M Tris (base), 150 mM glycine, 0.1% SDS,
0.1% 
-mercaptoethanol, and the lower chamber buffer consisting of
50 mM Tris (base), 75 mM glycine, and 0.05% SDS. The large gel
apparatus was placed in a walk-in refrigerator (4°C) and run for 24 h, the first 4 h at 275 V and the remainder at 180 V (constant voltage). After the run, the gels were stained for analysis of the
myosin isoforms present. Because the amounts of protein loaded were
~1 µg or less, a diamine silver staining procedure was used to view
the separations.
Analysis for metabolic enzymes. The samples were frozen and pulverized in liquid nitrogen for enzyme analysis. Enzymes involved in glycolysis [phosphofructokinase (PFK) and lactate dehydrogenase (LDH)] and terminal oxidation [citrate synthase (CS) and malate dehydrogenase (MDH)] were determined spectrophotometrically in duplicate. Enzyme activities were expressed as micromoles per gram muscle per minute (11).
Data collection and statistical analysis. Force and displacement waveforms were digitized at a rate of 100 samples/s and stored in an IBM PS/2 personal computer (data acquisition package: CODAS, Dataq Instruments). Data collection was initiated immediately before muscle activation and continued uninterrupted during the first 40 min of fatigue testing. Beyond this time, discrete data sets (30 s in length) were collected every 10 min. ANOVA was performed to detect differences among groups (TRUE EPISTAT, Epistat Services, Richardson TX). Where differences were found, Bonferroni-corrected Student's t-tests were performed to detect differences between paired groups. A two-sided P value of <0.05 was considered statistically significant. Results are expressed as means ± SE, unless otherwise stated.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Protocol I
This study was designed to measure the effects of long-term continuous-burst stimulation on LD muscle function and morphology. Muscles stimulated for either 6 or 12 wk produced a marked reduction in peak isometric force when tested under typical clinical stimulation conditions (Fig. 1A). Comparison of maximum isometric force generation with control muscles showed a 44.3% decrease in the 6-wk group and a 48.8% decrease in the 12-wk group. Strength differences were not significant between the two stimulation groups.
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Stimulated muscle groups displayed improved endurance capacity relative to control, as illustrated in Fig. 1B. Stroke work was reduced by 67% after the first 5 min of testing and then dropped 94% by the 10-min mark in the control group. At the conclusion of the 40-min test, control LD muscles retained only 2% of their initial work capacity. Conditioned muscles were fatigued by 17% in the 6-wk group and 18% in the 12-wk group after the first 5 min of testing and retained 47% (6 wk) and 57% (12 wk) of their initial stroke work at 40 min.
Fiber composition and CSA data for control and conditioned groups are
shown in Table 1. The percentage of type 1 fibers in both 6-wk and 12-wk groups was higher than control. The
percentage of type 2X fibers in both groups was lower than control.
Type 2A differences were not significant between stimulated and control groups. There were no differences in the CSA of type 1 fibers. However,
the CSA of type 2A fibers was decreased in the 6-wk group and the CSA
of type 2X was reduced in both 6-wk and 12-wk groups.
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Protocol II
This experiment was designed to measure the effects of continuous low-frequency stimulation on muscle fiber transformation. Histochemical examination of the muscles confirmed that there was a higher percentage in type 2A fibers after 6 wk of continuous single-pulse stimulation (Table 2). However, type 2A fibers were only provisional. When muscles were trained 6 more weeks, nearly half of the type 2A fibers were transformed into type 1 (Table 2). These data suggest that continuous single-pulse stimulation will, in the long term, lead to complete conversion to type 1 fibers and hence cannot be used to regulate phenotype expression to produce stronger fatigue-resistant muscle.
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Protocol III
Protocol III was designed to determine the effect of long-term intermittent-burst stimulation on muscle fiber phenotype expression, contractile function, fiber CSA, and metabolism. Results indicate that intermittent-burst stimulation not only prevents power loss in fatigue-resistant muscle, but can actually increase contractile function beyond baseline values. Intermittent-burst stimulation significantly increased isometric force generation (under clinically relevant stimulation conditions) compared with both the continuous-stimulation group (391%) and control muscles (175%) (Fig. 2A). On completion of the 3- or 8-h fatigue tests, peak isometric force was measured in the intermittent stimulation group after a 5-min rest period and was found to be higher than forces generated by the 6-wk continuous group before fatigue testing (392.3 ± 109.7 vs. 175.8 ± 24.4 g). Intermittent-burst stimulation also significantly improved chronic work capacity relative to continuous-burst stimulation (Fig. 2B). At the conclusion of the 40-min fatigue test, control LD muscles retained <1% of their initial work capacity. Stimulated muscles in the 6-wk continuous group fatigued by 61% (from 205.0 ± 22.4 to 124.3 ± 8.2 g · cm) after the first 10 min of testing and retained 35% (71.5 ± 19.5 g · cm) of their initial stroke work at 40 min. Muscles stimulated intermittently had the highest initial stroke work (449.7 ± 92.4 g · cm) and the highest remaining stroke work (234.7 ± 50.1 g · cm) at 40 min. Fatigue tests for the 12-wk intermittent group were continued to 3 or 8 h and yielded the following temporal stroke-work profile (in g · cm): 239.3 ± 54.7 at 1 h, 198.3 ± 39.0 at 2 h, 213.0 ± 61.0 at 3 h, 228 at 4 h, 258 at 5 h, 225 at 6 h, 181 at 7 h, and 165 at 8 h.
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In addition to changes in muscle function, concurrent changes in
muscular structure were also measured. Intermittent-burst stimulation
significantly increased the percentage and CSA of type 2A fibers.
Muscle fiber CSAs and relative distribution are shown in Figs.
3 and 4. The
percentage of type 1 fibers in both the 6-wk continuous group (52.1%)
and the 12-wk intermittent group (22.4%) was higher than that in
control (15.3%). Muscles in the 6-wk continuous group had a higher
percentage of type 1 fibers than that in the 12-wk intermittent group.
The percentages of type 2X fibers in the 6-wk continuous (12.0%) and
the 12-wk intermittent (19.5%) groups were lower than that in control
(62.8%). Type 2A differences were significant between stimulated and
control groups. The highest proportion of type 2A fibers (58.1%) was
in the 12-wk intermittent group. There were no differences in the CSA
of type 1 and 2X fibers between control and 12-wk intermittent groups. However, the CSA of type 2A fibers was increased in the
intermittent-stimulated muscles. The CSA of all type fibers was reduced
in the 6-wk continuous group.
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The electrophoretic mobility of the MHCs found in rabbit muscle fibers
was nearly equivalent to that of rat
MHC2X,
MHC2A, and
MHC
/slow as determined by
analysis of rat mixed vastus lateralis muscle myosin containing all
four rodent MHC isoforms (2B, 2X, 2A, /slow) (Fig.
5). Control LD muscles exhibited an overwhelming majority in the MHC2X
band, which matched with the distribution of type 2X fibers in Fig. 3.
Muscles in the 6-wk continuous group had majority bands in
MHC/slow and
MHC2A. However, intermittent-burst
stimulation consistently altered MHC composition of LD muscles,
resulting in conversion to MHC2A.
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Enzyme activities measured in these muscles are presented in Table
3. PFK and LDH levels were reduced only by
6-wk continuous stimulation, whereas MDH was not enhanced in the
stimulated groups. Significant increases in CS activity were seen in
both stimulated groups.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Observations from these three experiments provide insight into how phenotype expression may be controlled to improve function in chronically stimulated skeletal muscle. Traditional training techniques produce skeletal muscle comprising 100% type 1 fibers, which are very durable but slow and relatively weak. Thus the capacity of such "fully trained" muscles to move blood is limited. The ideal muscle for long-term cardiac assist would, in principle, comprise mostly type 2A fibers, which combine fatigue resistance, contractile power, and rapid relaxation rates. These fibers contain the fast MHC2A isoforms, display a high aerobic-oxidative potential, and contain large amounts of the fast isoform of the sarcoplasmic reticulum Ca2+-ATPase (15). The purpose of this study was to determine whether a significant population of type 2A muscle fibers can be maintained under stimulation conditions typically used for direct cardiac assistance.
Results from the first set of experiments (protocol I) indicate that continuous-burst stimulation effectively transforms muscle fibers from fast (type 2) to slow (type 1) phenotype, with a concomitant increase in fatigue resistance and a marked decrease in muscle strength. Data from protocol II suggest that continuous single-pulse stimulation will eventually lead to complete conversion to type 1 fibers, even if delivered at very low frequencies (i.e., 1 pulse/s). Taken together, these studies suggest that long-term continuous stimulation, either burst or single pulse, cannot be used to regulate phenotype expression to produce stronger fatigue-resistant muscle.
A third set of experiments (protocol III) was conducted to determine whether chronic burst stimulation combined with regular rest periods would produce a more powerful fatigue-resistant muscle. Intermittent-burst stimulation significantly increased maximum isometric force generation and chronic work capacity (at clinically relevant stimulation frequencies and burst duration) compared with both the continuous stimulation group and control muscles. In addition to changes in muscle function, concurrent changes in muscular structure were also observed. Intermittent-burst stimulation significantly increased the percentage of type 2A fibers relative to both control and 6-wk continuous groups. The percentage of type 1 fibers in both 6-wk continuous and 12-wk intermittent groups was also higher than control. There were no differences in the CSA of type 1 and 2X fibers between control and 12-wk intermittent groups. The CSA of type 2A fibers, however, was increased in muscles stimulated intermittently. The CSA of all fiber types was reduced in the 6-wk continuous group. The activity of enzymes involved in glycolosis (PFK and LDH) was reduced only by 6-wk continuous stimulation, whereas the oxidative enzyme MDH was not enhanced in either stimulated group. However, significant increases in the activity of a second enzyme involved in terminal oxidation (CS) was seen in both stimulated groups. Results suggest that a stable population of type 2A muscle fibers can be generated and maintained via intermittent-burst stimulation and that improvements in muscle strength and fatigue resistance can be achieved when fiber transformation to the type 1 phenotype is controlled.
Although fiber type distribution is critical to long-term contractile function, it is also important that the CSA of muscle fibers not decrease with stimulation. Tables 1 and 2 and Fig. 3 show that type 2X fibers occupy the most space in control LD muscle because they have the biggest CSA and the greatest number of fibers. This is why normal LD muscle is powerful but prone to fatigue. Both continuous-burst stimulation and continuous single-pulse stimulation produced muscles composed mostly of type 1 fibers with <30% CSA occupied by type 2A fibers. These changes were accompanied by a reduction in muscle strength and improvements in fatigue resistance. Muscles with the largest proportion of type 2A fibers (56% of total CSA) were conditioned via intermittent stimulation. With this fiber distribution, muscle strength and steady-state work capacity were seen to improve significantly (Fig. 2). The mechanism by which muscles composed mainly of type 2A fibers generate higher isometric force than those with mainly type 2X fibers (control muscle) is not known. One hypothesis is that the function of the neuromuscular junction, such as the maintenance of the acetylcholine receptor, is improved by intermittent stimulation.
It is important to note that measurements of peak isometric force reported here do not equate to the maximum force-generating capability of these muscles but rather indicate their capacity to perform under stimulation conditions generally accepted for clinical use (9, 13). In practical terms, preserving a given fiber type distribution over the long term requires that skeletal muscle be activated with the same pulse pattern used during training. We therefore chose to limit testing to a single stimulation regimen (25 Hz, 250-ms burst duration, 53 contractions/min) that was used to train the muscle and was proven safe for clinical use. Slightly higher stimulation frequencies (on the order of 35-40 Hz) might also prove effective for cardiac assist purposes.
Regarding the practical application of these results it should be stressed that, to maintain favorable LD fiber composition and contractile characteristics, cardiac assistance must be provided with the same on/off intervals used to train the muscle. With the use of the training protocol tested here for example, circulatory support could be provided for 12 h each day by harnessing energy from a single conditioned LD muscle. In this instance, cardiac assist would be provided during waking hours when the patient is most active and circulatory demands are at their peak. Continuous cardiac support could be provided by harvesting a second muscle to operate during the 12-h rest period of the first. Further studies are needed to determine whether similar results can be achieved using rest periods of shorter duration.
Perspectives
These findings suggest that the insertion of rest periods during chronic electrical conditioning preserves myofiber CSA and yields fatigue-resistant fiber distributions that are stronger than those achieved via conventional training techniques. The implication is that skeletal muscle phenotype can be controlled by manipulating stimulation patterns to produce fatigue-resistant muscle capable of providing clinically significant levels of work production. Previous efforts to adapt skeletal muscle for cardiac assistance have used continuous-burst stimulation protocols, which result in fatigue resistance at the expense of reduced muscle power. Our findings indicate that future clinical applications of stimulated skeletal muscle for cardiac assist should use intermittent stimulation protocols that produce more powerful fatigue-resistant muscles.| |
FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: D. R. Trumble, Cardiothoracic Surgery Research, Allegheny Univ. of the Health Sciences, Allegheny Campus (9th floor-South Tower), 320 East North Ave., Pittsburgh, PA 15212 (E-mail: trumble{at}pgh.auhs.edu).
Received 8 September 1998; accepted in final form 14 January 1999.
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
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