Hypoxia is Involved in Deep Tissue Injury Formation in a Rat Model
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Abstract: Pressure ulcers that develop from deep tissue are known as deep tissue injuries (DTI). Although several mechanisms, including ischemic hypoxia, are attributed to pressure ulcer formation, the mechanisms involved in DTI formation are still unclear. Previous studies have suggested that hypoxia is involved in DTI in vitro, but it has yet to be determined whether hypoxia is also involved in DTI in vivo. Therefore, this study aimed to investigate whether hypoxia is involved in DTI using a newly established DTI model. Rats were divided into control, low pressure DTI, and high pressure DTI groups. Results of wound healing tests indicated that more severe DTI resulted in prolonged healing time, more severe inflammation and muscle damage, higher levels of exudate creatine phosphokinase, and greater muscle edema. Increased hypoxia was observed in severe DTI—nuclear localization of hypoxia-inducible factor-1α was markedly increased in the high pressure DTI group, while the low pressure group showed more increased cytoplasm localization compared to the control group on day 3. Study results revealed that hypoxia is involved in DTI in vivo.
Address correspondence to:
Takashi Nagase, MD, PhD
Faculty of Medicine Building,
No. 5-301
Hongo 7-3-1, Bunkyo-ku
Tokyo 113-0033
Japan
Phone/Fax: +81-3-5841-3419
E-mail: tnagase@fb3.so-net.ne.jp
Pressure ulcers (PUs) markedly affect patients’ quality of life, morbidity and mortality, and account for considerable costs to the healthcare system. Approximately 2.5 million PUs are treated each year in acute care facilities alone with an estimated cost of $11 billion.1 The cost of treating a single pressure ulcer ranges from $500 to $40,000 depending on the severity of the wound.1 Although the prevalence of PUs is relatively low in Japan ([3.64%] calculated as existing cases of pressure ulcer patients divided by the number of all inpatients surveyed in a Japanese national surveillance study2) compared to the United States and European countries, the proportion of severe PUs in Japan is high; the proportions of Stage III and Stage IV PUs based on National Pressure Ulcer Advisory Panel (NPUAP) classification were estimated as 18.8% and 8.1% of all PUs, respectively.2 It has been shown that the high proportion of severe PUs is, at least in part, due to a newly recognized phenomenon, deep tissue injury (DTI).3,4
Previously, it was thought that PUs developed from the superficial skin into the deep tissue; recently, however, a new concept of DTI proposes that PUs can also develop from the deep tissue rising in muscle layers adjacent to bony prominences as a result of sustained loading.5 Therefore, DTIs are gaining increasing attention because they are difficult to detect and also deteriorate rapidly compared to Stage III and Stage IV PUs despite aggressive and optimal treatment.6 The NPUAP classifies suspected DTIs as a different form of PU.7 The mechanism involved in DTI formation must be investigated for early initiation of treatment to prevent deterioration, as described above. Four factors are hypothesized to be causes of PUs: hypoxia as a result of ischemia,8 reperfusion injury,9 impaired lymphatic function,10 and prolonged mechanical deformation of tissue cells.11 Although the mechanism of DTI might be similar to these four factors, the mechanism involved in DTI remains unclear.
Several studies have shown that hypoxia is one of the mechanisms involved in DTI. Gawlitta et al5,11 suggested the involvement of hypoxia and deformation in DTI in an in-vitro model using engineered skeletal muscle produced from murine muscle cells.
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