Oxygen delivery to skeletal muscle fibers: effects of microvascular unit structure and control mechanisms

2003 ◽  
Vol 285 (3) ◽  
pp. H955-H963 ◽  
Author(s):  
Arthur Lo ◽  
Andrew J. Fuglevand ◽  
Timothy W. Secomb

The number of perfused capillaries in skeletal muscle varies with muscle activation. With increasing activation, muscle fibers are recruited as motor units consisting of widely dispersed fibers, whereas capillaries are recruited as groups called microvascular units (MVUs) that supply several adjacent fibers. In this study, a theoretical model was used to examine the consequences of this spatial mismatch between the functional units of muscle activation and capillary perfusion. Diffusive oxygen transport was simulated in cross sections of skeletal muscle, including several MVUs and fibers from several motor units. Four alternative hypothetical mechanisms controlling capillary perfusion were considered. First, all capillaries adjacent to active fibers are perfused. Second, all MVUs containing capillaries adjacent to active fibers are perfused. Third, each MVU is perfused whenever oxygen levels at its feed arteriole fall below a threshold value. Fourth, each MVU is perfused whenever the average oxygen level at its capillaries falls below a threshold value. For each mechanism, the dependence of the fraction of perfused capillaries on the level of muscle activation was predicted. Comparison of the results led to the following conclusions. Control of perfusion by MVUs increases the fraction of perfused capillaries relative to control by individual capillaries. Control by arteriolar oxygen sensing leads to poor control of tissue oxygenation at high levels of muscle activation. Control of MVU perfusion by capillary oxygen sensing permits adequate tissue oxygenation over the full range of activation without resulting in perfusion of all MVUs containing capillaries adjacent to active fibers.

2007 ◽  
Vol 102 (5) ◽  
pp. 1985-1991 ◽  
Author(s):  
Ryan D. Maladen ◽  
Ramu Perumal ◽  
Anthony S. Wexler ◽  
Stuart A. Binder-Macleod

During volitional muscle activation, motor units often fire with varying discharge patterns that include brief, high-frequency bursts of activity. These variations in the activation rate allow the central nervous system to precisely control the forces produced by the muscle. The present study explores how varying the instantaneous frequency of stimulation pulses within a train affects nonisometric muscle performance. The peak excursion produced in response to each stimulation train was considered as the primary measure of muscle performance. The results showed that at each frequency tested between 10 and 50 Hz, variable-frequency trains that took advantage of the catchlike property of skeletal muscle produced greater excursions than constant-frequency trains. In addition, variable-frequency trains that could achieve targeted trajectories with fewer pulses than constant-frequency trains were identified. These findings suggest that similar to voluntary muscle activation patterns, varying the instantaneous frequency within a train of pulses can be used to improve muscle performance during functional electrical stimulation.


1983 ◽  
Vol 97 (3) ◽  
pp. 756-771 ◽  
Author(s):  
G F Gauthier ◽  
R E Burke ◽  
S Lowey ◽  
A W Hobbs

Immunocytochemical characteristics of myosin have been demonstrated directly in normal and cross-reinnervated skeletal muscle fibers whose physiological properties have been defined. Fibers belonging to individual motor units were identified by the glycogen-depletion method, which permits correlation of cytochemical and physiological data on the same fibers. The normal flexor digitorum longus (FDL) of the cat is composed primarily of fast-twitch motor units having muscle fibers with high myosin ATPase activity. These fibers reacted with antibodies specific for the two light chains characteristic of fast myosin, but not with antibodies against slow myosin. Two categories of fast fibers, corresponding to two physiological motor unit types (FF and FR), differed in their immunochemical response, from which it can be concluded that their myosins are distinctive. The soleus (SOL) consists almost entirely of slow-twitch motor units having muscle fibers with low myosin ATPase activity. These fibers reacted with antibodies against slow myosin, but not with antibodies specific for fast myosin. When the FDL muscle was cross-reinnervated by the SOL nerve, twitch contraction times were slowed about twofold, and motor units resembled SOL units in a number of physiological properties. The corresponding muscle fibers had low ATPase activity, and they reacted with antibodies against slow myosin only. The myosin of individual cross-reinnervated FDL muscle units was therefore transformed, apparently completely, to a slow type. In contrast, cross-reinnervation of the SOL muscle by FDL motoneurons did not effect a complete converse transformation. Although cross-reinnervated SOL motor units had faster than normal twitch contraction times (about twofold), other physiological properties characteristic of type S motor units were unchanged. Despite the change in contraction times, cross-reinnervated SOL muscle fibers exhibited no change in ATPase activity. They also continued to react with antibodies against slow myosin, but in contrast to the normal SOL, they now showed a positive response to an antibody specific for one of the light chains of fast myosin. The myosins of both fast and slow muscles were thus converted by cross-reinnervation, but in the SOL, the newly synthesized myosin was not equivalent to that normally present in either the FDL or SOL. This suggests that, in the SOL, alteration of the nerve supply and the associated dynamic activity pattern are not sufficient to completely respecify the type of myosin expressed.


1994 ◽  
Vol 125 (4) ◽  
pp. 893-902 ◽  
Author(s):  
P Caroni ◽  
C Schneider ◽  
M C Kiefer ◽  
J Zapf

The protracted absence of muscle activation initiates complex cellular and molecular reactions aimed at restoring functional neuromuscular transmission and preventing degenerative processes. A central aspect of these reactions is the sprouting of intramuscular nerves in the vicinity of inactivated muscle fibers. Sprouts emerging from terminal nerve branches and nodes of Ranvier can reestablish functional contacts with inactive muscle fibers, and this is an essential restorative process in pathological conditions of the neuromuscular system. Due to their rapid upregulation in inactive skeletal muscle fibers and their ability to induce nerve sprouting in adult muscle, insulin-like growth factors (IGFs) are candidate signaling molecules to promote restorative reactions in the neuromuscular system. In this study we have exploited the high affinity and specificity of IGF-binding protein 4 (IGF-BP4) and IGF-BP5 for IGF1 and IGF2 to determine whether these growth factors are involved in the nerve sprouting reaction in paralyzed skeletal muscle. In tissue culture experiments with sensory- and motoneurons we demonstrate that the neurite promoting activity of IGF1 is blocked by IGF-BP4, and that a similar IGF-BP-sensitive activity is detected in muscle extracts from paralyzed, but not from control muscle. In in vivo experiments, we show that local delivery of IGF-BP4 to Botulinum toxin A-paralyzed skeletal muscle effectively prevents nerve sprouting in that muscle. Our findings indicate that muscle IGFs play an essential role in intramuscular nerve sprouting. In addition, these findings suggest that IGFs are major signaling factors from inactivated muscle to promote local restorative reactions, including interstitial cell proliferation and nerve sprouting.


2011 ◽  
Vol 14 (4) ◽  
pp. 683-694 ◽  
Author(s):  
I. Otrocka-Domagała

Sensitivity of skeletal muscle to pro-apoptotic factors In mononuclear cells, apoptosis leads to DNA fragmentation and cell destruction, regardless of the activated pathway. As regards multinuclear cells, e.g. skeletal muscle fibers, apoptosis rarely induces the death of the entire cell, and it generally affects single nuclei. This process, referred to as nuclear apoptosis, has a negative effect on the expression of genes in the myonuclear domain. Apoptosis may be initiated in muscle cells by external stimuli which activate cell membrane death receptors as well as by internal stimuli which stimulate the mitochondrial release of pro-apoptotic proteins. Reactive oxygen species also play an important role in the initiation of apoptosis. In muscle cells, ROS are produced in response to extracellular reactions or by cell mitochondria. It is, therefore, believed that mitochondria play a central role in apoptosis within skeletal muscle. Skeletal muscles have a well-developed system that protects them against oxidative damage. Myogenic stem cells are an integral part of multinucleated myofibers, and they are critically important for the maintenance of normal muscle mass, muscle growth, regeneration and hypertrophy. The latest research results indicate that myogenic cells are more sensitive to oxidative stress and pro-apoptotic factors than well-differentiated cells, such as myotubes. The complex structure and activity of skeletal muscle prompted research into the role of apoptosis and its intensity under various physiological and pathological conditions. This review summarizes the results of research investigating control mechanisms and the apoptosis process in skeletal muscle fibers, and indicates unresearched areas where further work is required.


2005 ◽  
Vol 85 (4) ◽  
pp. 358-364 ◽  
Author(s):  
Chris M Gregory ◽  
C Scott Bickel

Abstract Electromyostimulation (EMS) incorporates the use of electrical current to activate skeletal muscle and facilitate contraction. It is commonly used in clinical settings to mimic voluntary contractions and enhance the rehabilitation of human skeletal muscles. Although the beneficial effects of EMS are widely accepted, discrepancies concerning the specific responses to EMS versus voluntary actions exist. The unique effects of EMS have been attributed to several mechanisms, most notably a reversal of the recruitment pattern typically associated with voluntary muscle activation. This perspective outlines the authors' contention that electrical stimulation recruits motor units in a nonselective, spatially fixed, and temporally synchronous pattern. Furthermore, it synthesizes the evidence that supports the contention that this recruitment pattern contributes to increased muscle fatigue when compared with voluntary actions. The authors believe the majority of evidence suggests that EMS-induced motor unit recruitment is nonselective and that muscle fibers are recruited without obvious sequencing related to fiber types.


1997 ◽  
Vol 82 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Geoffrey G. Emerson ◽  
Steven S. Segal

Emerson, Geoffrey G., and Steven S. Segal. Alignment of microvascular units along skeletal muscle fibers of hamster retractor. J. Appl. Physiol. 82(1): 42–48, 1997.—When muscle fibers contract, blood flow requirements increase along their entire length. However, the organization of capillary perfusion along muscle fibers is unclear. The microvascular unit (MVU) is defined as a terminal arteriole and the group of capillaries it supplies. We investigated whether neighboring MVUs along the fiber axis perfused the same group of muscle fibers by using the parallel-fibered retractor muscle. Hamsters were anesthetized and perfused with Microfil to visualize MVUs relative to muscle fibers. Fields of study, which encompassed five to seven neighboring MVUs along a muscle fiber, were chosen from the interior of muscles and along muscle edges. On average, MVUs were 1 mm in length, 0.50 mm in width, and 0.1 mm deep; segments of ∼30 fibers were contained in this tissue volume of 0.05 mm3 (20 MVUs/mg muscle). The total distance across muscle fibers encompassed by a pair of MVUs is designated “union” (U); the fraction of this distance common to both MVUs is designated “intersection” (I). The ratio of I to U for the widths of neighboring MVUs provides an index of MVU alignment along muscle fibers (e.g., I/U = 1.0 indicates complete alignment, where the fibers perfused by one MVU are the same as those perfused by the neighboring MVU). We found that I/U along muscle edges (0.71 ± 0.02) was greater ( P < 0.05) than the ratio measured within muscles (0.66 ± 0.02). A model predicted a maximum I/U of 0.58 with random MVU alignment. Thus measured values were closer to random than to complete alignment. These findings indicate that an increase in blood flow along muscle fibers requires the perfusion of many MVUs and imply that vasodilation is coordinated among the parent arterioles from which corresponding MVUs arise.


1981 ◽  
Vol 51 (3) ◽  
pp. 552-556 ◽  
Author(s):  
R. B. Armstrong ◽  
D. F. Peterson

This experiment was designed to determine if glycogen loss in active rat skeletal muscle fibers could be accentuated by periodic occlusion of blood to the muscles without significantly altering the numbers of types of fibers that lose glycogen. We attempted to augment glycogen loss by periodically occluding blood flow to the muscles while the animals ran on a treadmill. An occluder cuff was placed on the right common iliac artery of 10 rats. While the rats ran for 5 min at 26 m . min-1, blood flow to the right hindlimb was completely occluded for 16 +/- 5 (SD) s during every 30 s of the run. Glycogen loss in soleus (S), plantaris (P), and gastrocnemius (G) muscles was determined biochemically and histochemically. Muscles from both the occluded limb (S, P, and the deep red portion of G) and the nonoccluded limb (S and red G) of the runners showed significant glycogen loss compared with the controls. Furthermore, glycogen concentration was significantly lower in S, P, and red G of the occluded limb than in the same muscles of the nonoccluded limb. Significantly greater numbers of fibers within fiber type populations of P and G showed glycogen loss in the occluded limb, indicating that more motor units were recruited during the exercise bout in these muscles. The data suggest a sensitive link between motor unit recruitment and the metabolic condition of the contracting fibers, as the increased number of fibers showing glycogen loss presumably, resulted from fatigue of active units. We conclude that occlusion of blood flow to active muscles is not a feasible means of accentuating glycogen loss in active fibers while maintaining normal patterns of recruitment.


Author(s):  
I. Taylor ◽  
P. Ingram ◽  
J.R. Sommer

In studying quick-frozen single intact skeletal muscle fibers for structural and microchemical alterations that occur milliseconds, and fractions thereof, after electrical stimulation, we have developed a method to compare, directly, ice crystal formation in freeze-substituted thin sections adjacent to all, and beneath the last, freeze-dried cryosections. We have observed images in the cryosections that to our knowledge have not been published heretofore (Figs.1-4). The main features are that isolated, sometimes large regions of the sections appear hazy and have much less contrast than adjacent regions. Sometimes within the hazy regions there are smaller areas that appear crinkled and have much more contrast. We have also observed that while the hazy areas remain still, the regions of higher contrast visibly contract in the beam, often causing tears in the sections that are clearly not caused by ice crystals (Fig.3, arrows).


Author(s):  
Leonardo Hernández

The influence of Ca2+ and other divalent cations on contractile responses of slow skeletal muscle fibers of the frog (Rana pipiens) under conditions of chronic denervation was investigated.Isometric tension was recorded from slow bundles of normal and denervated cruralis muscle in normal solution and in solutions with free calcium concentration solution or in solutions where other divalent cations (Sr2+, Ni2+, Co2+ or Mn2+) substituted for calcium. In the second week after nerve section, in Ca2+-free solutions, we observed that contractures (evoked from 40 to 80 mM-K+) of non-denervated muscles showed significantly higher tensions (p<0.05), than those from denervated bundles. Likewise, in solutions where calcium was substituted by all divalent cations tested, with exception of Mn2+, the denervated bundles displayed lower tension than non-denervated, also in the second week of denervation. In this case, the Ca2+ substitution by Sr2+ caused the higher decrease in tension, followed by Co2+ and Ni2+, which were different to non-denervated bundles, as the lowest tension was developed by Mn2+, followed by Co2+, and then Ni2+ and Sr2+. After the third week, we observed a recovery in tension. These results suggest that denervation altering the binding capacity to divalent cations of the voltage sensor.


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