The main finding of the present study is that HPC protects skin from PI. For skin tissue that will be subjected to long-term surgical compression, local HPC can reduce the occurrence of PI, and this protective mechanism is achieved by stimulating HSP27 expression in tissues. This was also the first study to use HPC to prevent IAPUs in patients undergoing surgery in the supine position. Local HPC (using 43ºC warm water in a hot water bag) on the sacral skin can reduce the incidence of IAPUs in elective surgery patients.
At present, measures such as the use of dressings and skin emollients, nutritional supplements, physical support, and repositioning are commonly used to prevent IAPUs. However, there is no high-quality report on the relative effectiveness of these products.18
When organisms are exposed to harmful external stimuli (such as high-temperature heat shock, trauma, infection, and hypoxia), they quickly initiate a self-protective response that involves the activation of genes that encode protective HSPs.19 HSPs are a group of proteins expressed in the heat shock response. The HSP family can be divided into seven categories based on relative molecular weight: small HSP family, HSP10/60 family, HSP40 family, HSP70 family, HSP90 family, HSP110 family, and CCT family.20 There is evidence that HSP27 protects cells from apoptosis induced by various stimuli in vivo and in vitro. The expression of HSP27 can induce the expression of anti-apoptotic factors in the skin, reduce oxidative stress and aging, and thereby alleviate skin damage.21 HSPs play an important role in maintaining protein homeostasis and cell survival. Small-molecular-weight HSPs play a particularly important role, especially HSP27. Muramatsu et al.22 measured the expression of HSP27 by immunofluorescence in normal human skin after HPC for 1 hour, and found that HSP27 plays an important role in resistance to various environmental stresses in human skin. Small-molecular-weight HSPs can combine with a variety of proteins to enhance cellular protection to a range of stressors.23 Our results were consistent with these findings.
Many studies in both humans and animals have applied HPC to the skin, but the efficacy of HPC in preventing PI has not been clearly established. Several studies have confirmed that local heating of the skin can significantly improve tissue survival.24,25 The protective effects observed in these studies are thought to be due to the upregulation of HSP70 and HSP32 expression induced by high temperatures. In addition, Mehta et al.11 heated the skin of breast cancer patients in skin-sparing mastectomy and found that HPC could reduce skin necrosis and duration of hospital stay. In the present study, we found that the incidence of PI and the area of PI could be significantly reduced by heating rat dorsal skin. In human patients, we found that HPC could significantly reduce the incidence of IAPUs.
Ischemia/reperfusion injury is the main cause of PI.26,27 There is a great deal of evidence showing that HPC can protect heart,28 liver,29 and kidney30 tissue from hypoxia and ischemia/reperfusion injury in rats. Overexpression of HSP70 plays a direct role in improving myocardial and renal tolerance to ischemia/reperfusion injury in the heart and kidney.31,32 In hepatic ischemia/reperfusion injury, the improvement in microcirculation resulting from HPC-induced HSP70 expression is the main mechanism for these effects.29 However, other studies found that HSP70 was not detected during intestinal heat preconditioning,33 or in whole body hyperthermia at 40ºC.34 HSP72, HSP60, and HSP27 expression has been found to increase after HPC treatment of normal human skin, but the expression of HSP90 and HSP110 did not increase.35 However, some studies have also suggested that in chronic ischemic skin, HPC reduces ischemic tissue necrosis by improving microcirculation, an effect mediated by HSP32.36 Therefore, the mechanism underlying the protective effects of HPC remains controversial.
To elucidate the mechanism underlying the protective effects of HPC on PI, including the heat shock proteins involved, we observed both groups for 4 days after compression and selected tissues for histological analysis after 1 day. We chose the 1 day timepoint based on our observation that whether PI occurs tends to be determined in both groups after one day. The results of this study suggest that the protective effects of HPC on ischemic skin are related to the induction of HSP27, which is consistent with the results of Boxman et al.37 Boxman et al. 40 used chemicals to stimulate human skin and identified seven proteins as potential new epidermal markers for skin irritation. Among these seven proteins, HSP27 was identified as the most significantly upregulated, suggesting that HSP27 can be used as a sensitive marker for skin irritation. However, there were some differences between the present results and the HSP70 expression induced by HPC in the study mentioned above. In this previous study, the temperature used for HPC was 43ºC. However, in the current study, the final temperature of the heat transfer sheet material was 40.7 ± 0.3ºC owing to the use of three 30 minutes cycles at room temperature. While the temperature used in the present study was lower than those used in previous studies, it is also capable of inducing HSP. Our study has the following limitations: In the whole process of animal experiment, the sample size may be small. In addition, due to the limitation of the research conditions, we failed to analyze the microcirculation including arterioles, venules and capillaries in the compressed parts of the rats in the control group and the intervention group. During the human studies, there were fewer patients with Intraoperatively Acquired Pressure Ulcers, which may be related to the cotton cushion on the operating table to reduce the compression of sacrococcygeal. Considering the follow-up and survival rate, some patients with higher risk operations such as cardiac surgery and craniocerebral surgery were not included in the study. The main group of this study was digestive tract related diseases (esophageal cancer, gastric cancer, intestine), pancreatic disease, biliary disease, etc.). The sample size is not representative of all kinds of inpatients. In the future, we can consider increasing the sample size, and further explore the mechanism that HPC can alleviate the occurrence of PI.
In this study, we found that HPC treatment can significantly improve body temperature and enhance the skin healing process in both a rat PI model and surgical patients, indicating that HPC has protective effects against PI. This effect appears to be mediated by HSP27 upregulation. HPC can be implemented preoperatively in surgical patients and does not require intraoperative change of body position. Therefore, HPC may be a novel and effective means of preventing IAPUs for elective surgery patients.