Muscle apoptosis is induced in pressure-induced deep tissue injury

Pressure ulcer is a complex and significant health problem. Although the factors including pressure, shear, and ischemia have been identified in the etiology of pressure ulcer, the cellular and molecular mechanisms that contribute to the development of pressure ulcer are unclear. This study tested the hypothesis that the early-onset molecular regulation of pressure ulcer involves apoptosis in muscle tissue. Adult Sprague-Dawley rats were subjected to an in vivo protocol to mimic pressure-induced deep tissue injury. Static pressure was applied to the tibialis region of the right limb of the rats for 6 h each day on two consecutive days. The compression force was continuously monitored by a three-axial force transducer equipped in the compression indentor. The contralateral uncompressed limb served as intra-animal control. Tissues underneath the compressed region were collected for histological analysis, terminal dUTP nick-end labeling (TUNEL), cell death ELISA, immunocytochemical staining, and real-time RT-PCR gene expression analysis. The compressed muscle tissue generally demonstrated degenerative characteristics. TUNEL/dystrophin labeling showed a significant increase in the apoptotic muscle-related nuclei, and cell death ELISA demonstrated a threefold elevation of apoptotic DNA fragmentation in the compressed muscle tissue relative to control. Positive immunoreactivities of cleaved caspase-3, Bax, and Bcl-2 were evident in compressed muscle. The mRNA contents of Bax, caspase-3, caspase-8, and caspase-9 were found to be higher in the compressed muscle tissue than control. These results demonstrated that apoptosis is activated in muscle tissue following prolonged moderate compression. The data are consistent with the hypothesis that muscle apoptosis is involved in the underlying mechanism of pressure-induced deep tissue injury.

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Temporal differences in the influence of ischemic factors and deformation on the metabolism of engineered skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.01374.2006 ◽

2007 ◽

Vol 103 (2) ◽

pp. 464-473 ◽

Cited By ~ 68

Author(s):

Debby Gawlitta ◽

Cees W. J. Oomens ◽

Dan L. Bader ◽

Frank P. T. Baaijens ◽

Carlijn V. C. Bouten

Keyword(s):

Skeletal Muscle ◽

Cell Death ◽

Muscle Tissue ◽

Tissue Injury ◽

Glucose Deprivation ◽

Tissue Response ◽

Deep Tissue ◽

Deep Tissue Injury ◽

Tissue Metabolism ◽

Glucose Levels

Prolonged periods of tissue compression may lead to the development of pressure ulcers, some of which may originate in, for example, skeletal muscle tissue and progress underneath intact skin, representing deep tissue injury. Their etiology is multifactorial and the interaction between individual causal factors and their relative importance remain unknown. The present study addressed the relative contributions of deformation and ischemic factors to altered metabolism and viability. Engineered muscle tissue was prepared as previously detailed ( 14 ) and subjected to a combination of factors including 0% oxygen, lactic acid concentrations resulting in pH from 5.3 to 7.4, 34% compression, and low glucose levels. Deformation had an immediate effect on tissue viability {[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay}, which increased with time. By contrast, hypoxia evoked metabolic responses (glucose and lactate levels) within 24 h, but viability was only reduced after 48 h. In addition, lactic acidification downregulated tissue metabolism up to an acid concentration (∼23 mM) where metabolism was arrested and cell death enhanced. A similar tissue response was observed during glucose deprivation, which, at negligible concentration, resulted in both a cessation of metabolic activity and a reduction in cell viability. The combination of results suggests that in a short-term (<24 h) deformation, extreme acidification and glucose deprivation increased the level of cell death. By contrast, nonextreme acidification and hypoxia influenced tissue metabolism, but not the development of cell death. These data provide more insight into how compression-induced factors can lead to the onset of deep tissue injury.

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The Relative Contributions of Muscle Deformation and Ischemia to Pressure Ulcer Development

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80239 ◽

2012 ◽

Cited By ~ 1

Author(s):

Sandra Loerakker ◽

Gustav J. Strijkers ◽

Klaas Nicolay ◽

Frank P. T. Baaijens ◽

Dan L. Bader ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Tissue ◽

Pressure Ulcer ◽

Soft Tissues ◽

Tissue Injury ◽

Skeletal Muscle Tissue ◽

Ischemia And Reperfusion ◽

Deep Tissue ◽

Deep Tissue Injury ◽

Damage Process

Sustained mechanical loading of soft tissues covering bony prominences may lead to degeneration of skeletal muscle tissue. This can result in a condition termed deep tissue injury (DTI), a severe kind of pressure ulcer that initiates in deep tissue layers, and progresses towards the skin. Previously, we have provided evidence that in a controlled animal model, deformation is the main trigger for damage within a 2 h loading period [1,2]. Recently, we also showed that ischemia and reperfusion may contribute to the damage process during prolonged loading [3]. In the present study, we investigated the relative effects of deformation, ischemia, and reperfusion on the temporal and spatial damage process of skeletal muscle tissue during a 6 h period using magnetic resonance imaging (MRI) techniques.

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Diffusion of water in skeletal muscle tissue is not influenced by compression in a rat model of deep tissue injury

Journal of Biomechanics ◽

10.1016/j.jbiomech.2009.07.043 ◽

2010 ◽

Vol 43 (3) ◽

pp. 570-575 ◽

Cited By ~ 10

Author(s):

Bastiaan J. van Nierop ◽

Anke Stekelenburg ◽

Sandra Loerakker ◽

Cees W. Oomens ◽

Dan Bader ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Tissue ◽

Rat Model ◽

Tissue Injury ◽

Skeletal Muscle Tissue ◽

Deep Tissue ◽

Deep Tissue Injury

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Biomechanical Analysis of a Serious Pressure Ulcer Case in a Real-World Scenario

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-205038 ◽

2009 ◽

Author(s):

Eran Linder-Ganz ◽

Nogah Shabshin ◽

Amit Gefen

Keyword(s):

Cell Death ◽

Pressure Ulcer ◽

Tissue Injury ◽

Biomechanical Analysis ◽

Sigmoid Function ◽

Metabolic Demand ◽

Physical Damage ◽

Tissue Mass ◽

Ulcer Case ◽

Deep Tissue Injury

Deep tissue injury (DTI) is a serious pressure ulcer, characterized by necrotic tissue mass under intact skin. There is evidence that elevated tissue strains/stresses over prolonged times cause DTI, via paths of physical damage to cells, ischemia and impaired diffusion. Skeletal muscle is considered less tolerable to mechanical loads, likely because of higher metabolic demand and denser vascularization. When damaged in compression, muscle tissue stiffens up to ∼3-fold, depending on the magnitude and duration of loading [1]. Cell-death thresholds for loaded muscle, that are a Boltzmann-type downward-step sigmoid function of the magnitude of compression strain/stress and time, were developed based on meta-analysis of animal experiments [2]. These cell-death thresholds allow extrapolation of biological damage trends from computational stress analyses of muscle in load bearing postures.

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Assessment of Nursesʼ Knowledge and Practice in Prevention and Management of Deep Tissue Injury and Stage I Pressure Ulcer

Journal of Wound Ostomy and Continence Nursing ◽

10.1097/won.0b013e3181edec0b ◽

2010 ◽

Vol 37 (5) ◽

pp. 487-494 ◽

Cited By ~ 31

Author(s):

Arzu Karadağ Aydin ◽

Ayise Karadağ

Keyword(s):

Pressure Ulcer ◽

Tissue Injury ◽

Stage I ◽

Deep Tissue ◽

Deep Tissue Injury ◽

Knowledge And Practice

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The Effects of Pressure and Shear on Capillary Closure in the Microstructure of Skeletal Muscles: Computational Studies

ASME 2007 Summer Bioengineering Conference ◽

10.1115/sbc2007-176516 ◽

2007 ◽

Author(s):

Eran Linder-Ganz ◽

Amit Gefen

Keyword(s):

Muscle Tissue ◽

Skeletal Muscles ◽

Tissue Injury ◽

The Body ◽

Acute Ischemia ◽

Fe Model ◽

Mechanical Forces ◽

Deep Tissue ◽

Deep Tissue Injury ◽

Complete Closure

Deep tissue injury (DTI) is a serious and potentially deadly type of pressure ulcers, which initiate in deep muscle tissue under bony prominences of immobilized patients, and progress outwards towards the skin with no clear visual indications of the injury at the surface of the body. It had been suggested that DTI appear in muscle tissue first, due to the dense capillary vasculature in skeletal muscles which is susceptible to obstruction and occlusion by mechanical forces [1–3]. Though mechanical forces may cause capillaries to collapse and thus induce ischemic conditions in adjacent muscle cells [2], some investigators stipulated that ischemia alone cannot explain the etiology of DTI, and so, other mechanisms, particularly excessive cellular deformations must be involved [1]. We hypothesize that physiological levels of stresses and strains in muscle tissue under bony prominences — even when muscles are highly loaded as during sitting — do not cause complete closure of muscle capillaries, and therefore, do not cause an acute ischemia in muscles. If this is indeed the case, then ischemia cannot be the only factor contributing to DTI onset. In order to test our hypothesis, we developed a finite element (FE) model of the microstructure of skeletal muscle, at the level of muscle fascicles, and employed the model to determine the stress and strain levels required for causing partial and complete closure of capillaries.

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