Ischemia occurs when external pressure exceeds the capillary pressure, which was shown by Landis9^,10 in the 1930s to be 12 mm Hg on the venous end and 32 mm Hg on the arterial end. If the external compressive force exceeds capillary bed pressure (32 mm Hg), capillary perfusion is impaired and ischemia will ensue. Original dog studies demonstrated an inverse parabolic relationship between the amount of pressure and duration of exposure (Figure 98.5). Early studies demonstrated that pressure of 70 mm Hg applied over 2 hours was sufficient to cause pathologic changes in dogs. Dinsdale11 confirmed these results in a pig model; perhaps just as importantly, he was also able to demonstrate the absence of injury if pressure could be relieved for as little as 5 minutes, even with pressures as high as 450 mm Hg. Similarly, Daniel et al.12 demonstrated that pressure of 500 mm Hg applied for 2 hours, or pressure
of 100 mm Hg for 10 hours, was sufficient to cause muscle necrosis. Interestingly, it was not until pressure of 600 mm Hg was applied for 11 hours that ulceration of the skin could be seen. Not only did these results confirm the relationship between pressure and time, but they also demonstrated that the initial pathologic changes occurred in the muscle overlying the bone, followed by the more superficial soft tissue, involving the skin last.13 Several classic studies investigated pressure and its effects as it relates to location, time, and intensity in humans (Figures 98.1 and 98.2). In the supine position, the maximal recorded pressures were 40 to 60 mm Hg near the heels, buttock, and sacrum. In the sitting position, pressures were greatest near the ischial tuberosities.

Maintenance of soft-tissue integrity requires tightly regulated interactions between cells, growth factors, their receptors, extracellular matrix molecules, and a variety of proteases and their inhibitors. When tissue is injured by causes such as unrelieved pressure, there is a demargination and influx of cells responsible for inflammation. For injuries to heal, a series of events unfolds, including vasoconstriction/vasodilatation, coagulation, influx of proinflammatory cells like neutrophils and macrophages, and, finally, matrix formation/maturation. In chronic wounds, there is a breakdown in this sequence, leading to a non-healing wound. Altered immune function has been implicated in the development of pressure sores and molecular evidence points to an imbalance between matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). MMPs, especially 1 and 9, are key to cell signaling and migration, whereas TIMPs, especially 1 and 2, bind to these proteases and presumably protect uninjured tissues. Numerous subsequent studies have documented the presence of elevated levels of various MMPs and decreased levels of TIMPs in chronic wounds, or an imbalance between the levels of MMPs and TIMPs.14 In patients with spinal cord injuries, the loss of sympathetic tone results in vasodilatation of denervated tissues, which further intensifies this problem.

Approximately 80% of soft tissue mass is fluid. External pressure on soft tissue increases plasma extravasation, which leads to edema formation, a significant factor in pressure sore formation. Denervation contributes to pressure sore development through loss of blood vessel sympathetic tone and its subsequent vasodilatation, vessel engorgement, and edema. Circulatory deficiencies, such as heart failure, renal failure, and venous insufficiency, are risk factors for pressure sore formation in part due to their propensity to increase edema in dependent soft tissue. On a molecular level, inflammatory mediators such as prostaglandin E₂ released in response to the trauma of compression increase leakage through the cell membranes and increase interstitial fluid accumulation.