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Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada H2L 4M1
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We hypothesized that the amount of sarcolemmal injury is directly related to the total tension time (TTtot), calculated as mean tension × total stimulation time. Diaphragm strips from Sprague-Dawley rats were superfused at optimal muscle length with Krebs containing procion orange to identify sarcolemmal injury. TTtot was induced by stimulation with 100 Hz for 3 min at duty cycles of 0.02, 0.15, 0.3, and 0.6, or with continuous contractions at 0.2, 0.4, 0.6, and 1.0 of maximal tension. A significant positive correlation between TTtot and the percentage of fibers with injured sarcolemma (r2 = 0.63, P < 0.05) is seen. Stimulation (at 100 Hz, duty cycle = 1) resulted in fast fatigue with low injury, likely caused by altered membrane conductivity. Stimulations inducing the largest injury are those showing progressive force loss and high TTtot, where injury may be due to activation of membrane degradative enzymes. The maximal tension measured at 20 min poststimulation was inversely related to the number of fibers injured, suggesting loss of force is caused by cellular injury.
fatigue; isometric contraction; membrane damage; procion; diaphragm muscle
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE MECHANISMS BY WHICH SKELETAL muscles develop injury have been extensively studied in limb muscles, where pliometric contractions were found to be most damaging. Injury has mainly been attributed to high stress and strain, leading to tears in the muscle fibers (12-14). The diaphragm, on the other hand, contracts mainly miometrically and seldom develops pressure >40% of maximal. Our laboratory (19) has previously studied the injury rate of dog diaphragm exposed to mild inspiratory resistance and found that there are injuries that occur relatively more often in the sarcolemma than in the sarcomere. There were no significant injuries while the dogs were breathing at rest (19).
Therefore, whereas the high tension theory as a cause of injury is convincing in eccentric contractions (EC), it does not fully explain the injuries seen in the diaphragm at relatively lower forces. We propose that the amount of injury should be directly related to the level of total tension time (TTtot; the integral of tension developed in the time of loading), a parameter that increases by the level of tension time of contractions.
To test this hypothesis, we measured, in isometric diaphragm strips, the effects of stimulation patterns of both nonfatiguing and fatiguing stimulation. We measured the TTtot developed over a 3-min stimulation protocol, together with the quantity of fibers showing sarcolemmal injury, and the force recovery over 40 min and related them to the amount of injury.
Diaphragm injury may explain the low endurance and prolonged weakness seen after inspiratory resistive loading, which cause fatigue (19).
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Animal care and preparation. Animal care was conducted under the guidelines of the Canadian Council of Animal Care, with all aspects of the experimental protocols being approved by the institutional animal care and ethics committee. Experiments were performed on mature (250-300 g) male Sprague-Dawley rats from Charles River (St-Constant, Quebec). On their receipt, rats were assigned to square wire-mesh cages in a temperature-controlled (26°C) room with a 12:12-h light-dark cycle. Rats were given free access to standard stock Purina rat chow diets and water.
General procedures. Animals were anesthetized with pentobarbital sodium (50 mg/kg) via an intraperitoneal injection. The entire diaphragm was rapidly excised and immersed in oxygenated Krebs solution for further dissection. Diaphragm strips (3-4 mm wide) were dissected from both right and left sides of the midcostal diaphragm with the fiber insertion at the ribs and the central tendon left intact. The average muscle strip length at optimal muscle length (Lo) was 20.3 ± 1.1 (SE) mm. The average strip weight was 36.7 ± 2.0 mg (wet weight). The strips were mounted in a vertically positioned muscle chamber, with the rib securely clamped to the bottom of the chamber. The central tendon was connected to the force transducer (Kent, Nagashigi, Japan) with no. 4.0 silk thread. The strips were positioned between two sets of platinum electrodes (mounted in the muscle chamber). These electrodes were used to deliver the electrical field stimulation. The strips were continuously superfused (5-10 ml/min at 35°C) with fresh Krebs solution, which had a composition of (in mM) 118 NaCl, 4.7 KCl, 2.5 CaCl2, 1.2 MgSO4, 1 KH2PO4, 25 NaHCO3, and 11.0 glucose. The Krebs solution was equilibrated with 95% O2-5% CO2 to a pH of 7.35 and was bubbled with this gas mixture throughout the experiment. The fluorescent molecular tracer procion orange 14 (Sigma Chemical) was added to the Krebs solution (0.15% wt/vol) for the identification of fibers that undergo sarcolemmal disruption. The total exposure time of the strips to the bath solution containing procion orange was 90 min in all studies.
After an equilibration period of 15 min, diaphragm strips were adjusted to Lo, where the Lo was defined as the length at which peak isometric tetanic tension was produced. The muscle strips were stimulated (model S48 stimulator, Grass, Quincy, MA) to achieve maximum tetanic force, where the final voltage (~6 V) was set at 1.3 times the voltage that gave maximal force, the stimulation frequency was 100 Hz, and the train duration was set at 600 ms (the train duration of a single rectangular current pulse was 0.3 ms). After the 3-min stimulation with the muscle recovering, contractility was measured by applying 600-ms tetanic stimulations, which were contractions given at 100-s intervals for 40 min until the recovery period was completed. The force signals produced by tetanic contractions were digitized (DT2821; Data Translation, Marlboro, MA) at a sampling rate of 1,000 Hz and fed into a personal computer for later analysis. The force was expressed in newtons per square centimeter, and the muscle cross-sectional area was calculated as the ratio of trimmed muscle mass (g) to strip length (cm) × 1.056 g/cm3 (muscle density) (6). The temperature of the bath was maintained at 35°C for the duration of the experiment.Experimental protocols.
In protocol 1, the diaphragm strips (n = 37) were
subjected to repeated 100-Hz maximal isometric tetanic contractions for 3 min at the following initial duty cycles (DCs): 0.02, 0.15, 0.3, and
0.6. DCs were changed by adjusting the rest-time interval. In
protocol 2, four groups of muscle strips were stimulated
continuously for 3 min. The sustained isometric contractions were
initiated at either 20, 40, 60, or 100% of maximal tension by
adjusting the stimulation frequency between 6 and 100 Hz. Table
1 lists the number of diaphragm strips in
each group, the stimulation frequency, the tension time index (TTI)
[tension/tensionmax × C/(C + R), where
tensionmax is maximum tension, C is contraction time, and R
is rest time] as a unitless parameter to describe the stimulation
pattern at the start of each protocol, DC, relative force,
TTtot, fraction of injured cells, and the number of
stimulation trains per 3 min for each protocol. In addition, 19 paired
strips were set at Lo in the muscle chamber without
stimulation and served as control for cell membrane injury counting.
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dF/dt, respectively), the muscle
contractile properties, which were measured from the dF/dt of
tetanic contractions (9); and the tension at 600 ms relative to the
peak tetanic tension within the contraction. Figure 2 shows the time course of PF during the
3-min stimulation period (A) and the recovery period
(B) for protocol 1. The TD50 is the time to
reach 50% decay from the PF at the start of the stimulation protocol.
The PF20 is measured at 20 min into the recovery period. Figure 2, C and D, shows data from protocol 2,
indicating the TD50 and PF20 values. Both
protocols were tested up to 40 min after the 3-min stimulation period.
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Quantification of fiber sarcolemmal injury.
Immediately after the recovery period was completed, the muscle strips
were rinsed in normal Krebs solution for 5 min, quick-frozen in
isopentane precooled with liquid nitrogen, and preserved at 80°C. Serial sections (10 µm thick) were cut in the
transverse plane with a cryostat microtome (Leica Cryocut 1800, Heidelberg, Germany). To assess the amount of sarcolemmal injury,
transverse frozen sections of rat diaphragm were randomly selected and
photographed by using epifluorescence microscopy (Carl Zeiss D-7082,
Oberkochen, Germany). Approximately 10-15 microscopic fields per
muscle were analyzed by using the fluorescein filter setting at a
magnification level of ×100. Muscle fibers that demonstrated a
clear increase in cytoplasmic fluorescence (i. e., fibers containing
the procion orange tracer dye) were counted, and the percentage of
dye-positive fibers on each diaphragm section was determined. Figure
3 shows samples of muscle exposed to
different TTI. The areas with sectioning artifacts (folds, tears, etc.)
were excluded, as were the edges of the sections to avoid areas damaged
by the muscle dissection. A minimum of 1,000 diaphragm fibers was
counted in each muscle.
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Statistical analysis. Results are expressed as mean values ± SE, unless otherwise indicated. Differences between groups were assessed by one-way ANOVA with post hoc application of the Student-Newman-Keuls test. Statistical significance was set at P < 0.05, unless otherwise specified.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Two protocols were carried out. In protocol 1, stimulation was done with supramaximal voltage at 100 Hz. The DC was varied to generate initial TTI values of 0.02-0.6. In protocol 2, the DC was constant at 1 (continuous contraction). The initial force was varied by changing the frequency of stimulation. Parameters defining the stimulation patterns are shown in Fig. 1.
Figure 2A shows the time course of force obtained from
protocol 1 during 3 min of stimulation. Figure 2B shows
the force elicited every 100 s, via a 600-ms electrical stimulation
given over the 40-min recovery period. The rate of force decay
increases in direct relationship to the initial TTI. The lowest TTI,
0.02, shows no force loss; fatigue becomes evident at all the other
initial TTI values. The rate of decay of force was quantified as
TD50 (the time of decrease of force to 50% of maximal
force), and values are shown in Table 2.
Time course of PF recovery is shown in Fig. 2B. Notice that the
TTI 0.02, a nonfatiguing protocol, shows the same PF at the start and
the end of the run (PFst and PFend, respectively). The PF20, or force measured after 20 min
poststimulation, was ~93% of control. At fatiguing protocols, force
decreased the most at TTI 0.6 and 1.0 with levels >88%. Force
recovery from fatigue runs was incomplete. The highest recovery in
force was seen at TTI 1.0 (74%), and the lowest was at TTI
0.3-0.6 (reaching 55-60% of control and deteriorating
further with time). Similar parameters measured in protocol 2 are shown in Fig. 2, C and D. Values of parameters
related to muscle contractility are shown in Table 2. The percentage of
fibers found to have procion in the cytoplasm is expressed as a
percentage of total fibers counted for each protocol; values are
included in Table 1. Samples of sarcolemmal injury are illustrated in
Fig. 3.
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The rate of rise of force at the start of the 3-min stimulation period and at the end (dF/dtend) is an indication of the contractile mechanism deterioration. It was not affected in the nonfatigue run. The largest decrease in the rate of rise of force occur at TTI 0.3-0.6 (19-27%).
The dF/dt is an expression of cytosolic Ca2+
management. A slow relaxation rate is seen when there is free
Ca2+ accumulation intracellularly (3). There was no change
between dF/dt at the start of the stimulation period and
dF/dtend in the nonfatigue run. The highest decay
is seen at initial TTI 0.6 in protocol 1 and at initial TTI 1.0 in protocol 2, with a decrease to 2-5% of
dF/dt at the start of the stimulation period
(dF/dtst).
The loss in dF/dt is a function of the intensity of the
stimulation pattern. dF/dt20 expresses the
recovery of relaxation rate after 20 min of rest. Compared with
dF/dtst, we note a decreased value of
dF/dt20 in all runs except the nonfatiguing
run (TTI 0.02). On the other hand, dF/dt20
values are considerably higher than dF/dt at the end of
the stimulation period (dF/dtend) of the
stimulation run, showing some recovery. The run at TTI 0.6 recovered
partially, with ~50% of dF/dtst. Figure
4 shows the dF/dtend and dF/dtend,
demonstrating a similar loss in both.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The objective of this study was to establish if there was a
relationship between the amount of injury and TTtot. Our
major findings indicate the following. 1) The TTtot
developed by the muscle shows a direct relationship to the amount of
sarcolemmal injury, as indicated in Fig.
5A. 2) The capacity to
recover force after fatigue is inversely proportional to the number of
injured fibers (Fig. 5B). 3) Neither the maximal level of
tension developed nor the DC alone was related to the amount of injury.
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Critique of methods to measure sarcolemmal injury. Many techniques have been used to assess the magnitude of sarcolemmal injury. Injecting procion orange into the blood circulation in vivo or adding it to the muscle bath are simple and highly sensitive techniques for the detection of sarcolemmal gaps in the diaphragm fibers (19). Procion orange 14, a fluorescent compound with a small molecular weight, is impermeable in healthy muscle membranes; it enters only into the cytoplasm when there is a membrane gap. The advantage of the procion orange technique for in vitro studies of the diaphragm is that the muscle is both flat and thin (between 15 and 25 cells across) and thus allows a good diffusion of the Krebs solution to the central fibers and creates a clear image of the distribution of fibers with sarcolemmal injury. Other techniques, such as measuring the amount of proteins released from the cytoplasm, such as myoglobin or enzyme efflux [e.g., creatine kinase and lactate dehydrogenase (18) or antiserum albumin (11)], have all been used with success in both in vivo and in vitro skeletal and cardiac muscle studies. In our experiments, however, the total amount of enzyme or protein release from the cytoplasm would be relatively small, because the muscle mass is 36.7 ± 2.0 mg and because the enzyme or protein efflux would dilute very rapidly in the 50-ml muscle bath. Furthermore, the flow rate of the Krebs solution in the bath is large at 5-10 ml/min. Consequently, whatever the amount of enzymes or proteins released by injured muscle fibers, it would quickly become diluted and would rapidly be removed from the bath. The sample taken from the bath would probably underestimate and vary considerably in the actual measurement of damage. Therefore, we believe that, for studies of the diaphragm in a muscle chamber preparation, the fluorescent dye (procion orange) technique is more sensitive than measuring the release of enzymes or proteins into the muscle bath.
Use of TTI and TTtot to evaluate muscle injury.
We use the term TTI to define the pattern of stimulation in terms of
tension/tensionmax × DC (unitless). The term
TTtot is defined as the time integral of tension throughout
the 3-min protocol. How do TTI and TTtot relate? In
nonfatiguing contractions, they are linearly related. In fatiguing
contractions, the correlation is shown in Fig.
6, suggesting a deterministic bimodal
relationship. A progressive increase in TTI up to ~0.4-0.6
results in a linear increase in TTtot, with the peak being
reached at TTI of ~0.6. Beyond 0.6, TTtot decreases. In
the ascending leg (TTI from 0.15 to 0.4), the increase in
TTtot correlates directly to the increase in sarcolemmal
injury. This may be caused via a cytosol Ca2+ increase,
activating Ca2+-sensitive degradative pathways, which leads
to SR and membrane lesions. Stimulation at TTI of 1.0 results in a
rapid fatigue, a low value in TTtot, and a lower level of
injury. It describes a parabolic relationship. The decrease in
TTtot at TTI of 0.6-1.0 may be due to the development
of high-frequency fatigue affecting mainly the membrane depolarization,
thereby causing loss of tension, which protects the integrity of cell
metabolism and structure. TTI 0.02 is a nonfatigue pattern, and little
injury is expected.
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Proposed mechanisms of sarcolemmal injury. Most of the hypotheses that support "mechanical stress" as a cause of muscle injury during exercise are based on studies of EC. EC indeed produce higher tension per cross-sectional area than do concentric contractions. It was proposed that EC stress all of the structural elements of the muscles, which are in series, and, eventually, pull apart the sarcomere with disruption of the A and Z bands (2), as well as cause disruption of the plasma membrane and sarcolemma by shearing forces (14). Also, the amount of sarcolemmal injury seen with pliometric contractions has been found to be directly correlated with the magnitude of mechanical stress in the mdx mouse, a strain lacking the dystrophin gene (15). Thus these observations support the hypothesis that cytoskeletal proteins that link the sarcolemma to contractile proteins are involved (17). In isometric contractions, there is evidence that the total free Ca2+ concentration is elevated by exercise. A high Ca2+ level in the cytosol is related to fiber injury (7) as well as to the protein release and cytosolic enzyme efflux (10). The elevation of cytosol Ca2+ can be secondary to disruption of SR membrane or to extracellular influx of Ca2+ (14).
In our work, the time at which the muscle strips lost 50% of their maximal force (TD50) is strongly related to the stimulation TTI, as shown in Table 2. The lowest initial TTI (0.02) did not produce fatigue and also showed a low TTtot (Table 1). The highest TTI (1.0) produced a precipitous decrease in force (TD50 of 12 s), and, therefore, TTtot also remains low. This fatigue can be defined as high frequency and occurs at the T tubular level because of a moderate and fully reversible state of action potential propagation failure, which is supported by the changes in the values of the percentage of force generated at 600 ms within a contraction to maximal force (13) (Table 2). Here, the cell's physical integrity is not affected, because the failure to contract occurs at the excitation phase rather than at the sarcomere level. The runs with intermediary levels of TTI result in higher TTtot and a higher amount of injury. In the runs with intermediary levels of TTI and maximal TTtot, the fatigue is likely to be originated at the contractile level. For example, thedF/dt at the
end of the 3-min run (dF/dtend, Table 2)
decreases considerably and shows an inverse relation with the
TTtot developed. The dF/dt decreases
significantly in runs having a high percentage of injured fibers.
Other mechanisms have been shown to participate in the process of
sarcolemmal injury. For example, it has been reported that oxygen free
radicals are formed in the diaphragm during inspiratory resistive
breathing, and these radicals cause impaired diaphragm function (1).
Recent reports support the view that the increase in oxygen free
radicals influences Ca2+ movements in the cell by modifying
the proteins associated with the Ca2+ release process (5, 11a).
In real life, the diaphragm is designed to shorten, rather than
generate, high force. In fact, shortenings of 20% from
Lo are common during hyperpnea, changes in body
position, or continuous positive airway pressure. We suspect length is
a relevant factor in diaphragm injury. This aspect was not explored in
this work, where length was constant (8, 16).
In conclusion, the integrity of skeletal muscle fiber membrane is
essential for muscle fiber homeostasis and for the performance of
muscle tension. Our results indicate that the amplitude of force
generation, both during the fatiguing protocol and in the subsequent
recovery period, was greatly affected by the initial tension time
protocol of stimulation applied during a 3-min period. The
TTtot developed was directly related to the number of
muscle fibers having sarcolemmal injury. The force recovery after 20 min of rest is inversely related to the amount of fiber injury. This is
in agreement with previous results reported by West-Jordan and
colleagues (18), who showed that the maximal creatine kinase efflux is
inversely related to the force recovery during poststimulation. We
found injury at effort levels in the range of those causing fatigue.
Fiber injury may be a cause of prolonged force loss after strong efforts.
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ACKNOWLEDGEMENTS |
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A. E. Grassino was supported by Medical Research Council of Canada, and A. S. Comtois by Fonds de la Recherche en Santé du Québec and the Association Pulmonaire du Quebéc.
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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: A. E. Grassino, Centre de Recherche du CHUM, Campus Notre-Dame, 1560 Rue Sherbrooke Est., Porte I-2158, Montreal, Quebec, Canada H2L 4M1 (E-mail: agrassino1{at}hotmail.com).
Received 11 June 1998; accepted in final form 31 August 1999.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Anzueto, A.,
G. S. Supinski,
S. M. Levine,
and
S. G. Jenkinson.
Mechanisms of disease: are oxygen-derived free radicals involved in diaphragmatic dysfunction?.
Am. J. Respir. Crit. Care Med.
149:
1048-1052,
1994[ISI][Medline].
2.
Armstrong, R. B.,
G. L. Warren,
and
J. A. Warren.
Mechanisms of exercise-induced muscle fiber injury.
Sports Med.
12:
184-207,
1991[ISI][Medline].
3.
Baker, A. J.,
and
M. W. Weiner.
Force decline during muscle relaxation promotes calcium release to the cytosol.
Am. J. Physiol. Cell Physiol.
273:
C85-C91,
1997
4.
Bellemare, F.,
D. Wight,
C. M. Lavigne,
and
A. Grassino.
Effect of tension and timing of contraction on the blood flow of the diaphragm.
J. Appl. Physiol.
54:
1597-1606,
1983
5.
Brotto, M. A.,
and
T. M. Nosek.
Hydrogen peroxide disrupts Ca2+ release from the sarcoplasmic reticulum of rat skeletal muscle fibers.
J. Appl. Physiol.
81:
731-737,
1996
6.
Close, R. I.
Dynamic properties of mammalian skeletal muscles.
Physiol. Rev.
52:
129-197,
1972
7.
Duan, C.,
M. D. Delp,
D. A. Hayes,
P. D. Delp,
and
R. B. Armstrong.
Rat skeletal muscle mitochondrial [Ca2+] and injury from downhill walking.
J. Appl. Physiol.
68:
1241-1251,
1990
8.
Easton, P.,
J. W. Fitting,
R. Arnoux,
A. Guerraty,
and
A. Grassino.
Costal and crural diaphragm function during CO2 rebreathing in awake dogs.
J. Appl. Physiol.
74:
1406-1418,
1993
9.
Esau, S. A.,
F. Bellemare,
A. Grassino,
S. Permutt,
C. Roussos,
and
R. L. Pardy.
Changes on relaxation rate with diaphragmatic fatigue in humans.
J. Appl. Physiol.
54:
1353-1360,
1983
10.
Helliwell, T. R.,
M. J. Jackson,
J. Phoenix,
P. MacLennan,
J. West-Jordan,
and
R. H. Edwards.
Immunohistochemical and biochemical indicators of muscle damage in vitro: the stability of control muscle and the effects of dinitrophenol and calcium ionophore.
Int. J. Exp. Pathol.
75:
329-343,
1994[ISI][Medline].
11.
Kasper, C. E.
Sarcolemmal disruption in reloaded atrophic skeletal muscle.
J. Appl. Physiol.
79:
607-614,
1995
11a.
Lamb, G. D.,
and
D. G. Stephenson.
Oxidation effects in fatigue: unphysiological responses to "depolarization" in skinned muscle fibers.
J. Appl. Physiol.
82:
2054-2056,
1997.
12.
Lieber, R. L.,
T. M. Woodburn,
and
J. Friden.
Muscle damage induced by eccentric contractions of 25% strain.
J. Appl. Physiol.
70:
2498-2507,
1991
13.
Light, P. E.,
A. S. Comtois,
and
J. M. Renaud.
The effect of glibenclamide on frog skeletal muscle: evidence for K+ ATP channel activation during fatigue.
J. Physiol. (Lond.)
475:
495-507,
1994
14.
McNeil, P. L.,
and
R. Khakee.
Disruptions of muscle fiber plasma membranes. Role in exercise-induced damage.
Am. J. Pathol.
140:
1097-1109,
1992[Abstract].
15.
Petrof, B. J.,
J. B. Shrager,
H. H. Stedman,
A. M. Kelly,
and
H. L. Sweeney.
Dystrophin protects the sarcolemma from stresses developed during muscle contraction.
Proc. Natl. Acad. Sci. USA
90:
3710-3714,
1993
16.
Road, J. D.,
A. M. Leevers,
and
A. Grassino.
The effect of continuous positive airway pressure versus positive end-expiratory pressure on the diaphragm.
J. Crit. Care
6:
136-142,
1991.
17.
Tidball, J. G.
Force transmission across muscle cell membranes.
J. Biomech. 24, Suppl.
1:
43-52,
1991.
18.
West-Jordan, J. A.,
P. A. Martin,
R. J. Abraham,
R. H. Edwards,
and
M. J. Jackson.
Energy metabolism during damaging contractile activity in isolated skeletal muscle: a 31P-NMR study.
Clin. Chim. Acta
203:
119-134,
1991[ISI][Medline].
19.
Zhu, E.,
B. J. Petrof,
J. Gea,
N. Comtois,
and
A. E. Grassino.
Diaphragm muscle fiber injury after inspiratory resistive breathing.
Am. J. Respir. Crit. Care Med.
155:
1110-1116,
1997[Abstract].
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, example of noninjured fibers (negative fibers);
arrow points to typical sample area that was excluded in quantification
of injured fibers for all samples analyzed.
, protocol 1.
