Towards the prevention of pressure ulcers

Abstract

This study is centred around preventing pressure ulcer (PU) progression by first understanding what happens in an early experimental PU and later attempting to prevent experimental PU progression. Pressure ulcer is one of the costliest and physically debilitating condition in the 20th century. While there are many guidelines on preventing PU progression, it continues to be prevalent. This warrants for a better understanding of what causes a PU with the aim of treating the cause. Ischaemia reperfusion (I/R) injury has been one of the potential causes of PU. This injury happens as bony prominences are rested on surfaces for relatively long periods of time where tissues experience ischaemia. Tissue injury is then exacerbated by reperfusion upon pressure relief. Ischaemia reperfusion injury is well studied in ischaemic stroke and cardiac infarction situations. In both organs, connexin43 is implicated in the pathogenesis of I/R injuries and modulating connexins in these organs can reduce I/R injury. Regarding the skin, publications report the creation of an experimental PU model by inducing I/R injuries. However, few experimental PU models are characterised to study the early events of an experimental PU. To do so, an early experimental PU model is optimised and characterised. With this early experimental PU model, epidermal Cx43 expression was demonstrated to be up regulated in the skin after I/R injury at 4 h and 24 h. The up regulation of epidermal Cx43 is incidentally an observation also seen in publications regarding wound edges of human PUs. Epidermal Cx43 up-regulation was found to be prevented by treating the early PU model with Cx43 antisense oligonucleotide (Cx43asODN). Necroptosis, a cell death pathway, is also known to be involved in I/R injury. Up-regulation of both necroptosis related proteins, high mobility group box 1 protein (HMGB1) and receptor-interacting seine/threonine-protein kinase 3 (RIP3), were observed in the epidermis. Expectedly, epidermal high mobility group box 1 protein (HMGB1) and receptor-interacting seine/threonine-protein kinase 3 (RIP3) up-regulation was also inhibited when treated with Cx43asODN. Furthermore, experimental PU progression was prevented when Cx43asODN was administered in a more severe experimental PU model. These findings suggest that the treatment of Cx43asODN was successful in inhibiting I/R injury which resulted in the prevention of experimental PU progression.