Ischemia-reperfusion injury of the appendicular musculoskeletal system

Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including

• "Ischemia": an inadequate blood supply to an organ or part of the body.^{[citation needed]}
• "Reperfusion": the restoration of blood flow to an organ or tissue after having been blocked.^{[citation needed]}

Mechanisms and basic science

IR and biomarkers

Serum lactate level is a proxy measure of tissue oxygenation. When tissues do not have adequate oxygen delivery (i.e., are ischemic), they revert to less efficient metabolic processes, producing lactic acid.^{[citation needed]}

Myoglobin is released from damaged muscle, as in the case of ischemia.^{[citation needed]}

Serum creatinine and BUN may be elevated in the setting of acute kidney injury.^{[citation needed]}

IR and epigenetics

IR and stem cells

While some investigations suggest a possible beneficial effect of

Stem cells have been implicated in the regeneration of skeletal muscle after traumatic and blast injuries, and have been shown to hone to muscle damaged after exercise.^[citation needed]

Clinical implications

• Systemic effects of IR injury

During periods of ischemia, cellular break down products accumulate in the local tissue. Once reperfusion occurs, these cellular products are returned to the systemic circulation, and are exposed to other organs. Organs involved in filtration (e.g., the kidneys and the liver), may be overwhelmed by the high load of cellular break down products, and face injury themselves (e.g., acute kidney injury).^{[citation needed]}

• Tissue swelling and fasciotomy

Following ischemia, reperfusion induces local tissue swelling. Tissue that swells within a confined space (e.g., muscle within its overlaying fascia) is susceptible to compartment syndrome in this situation. Recognizing this, surgeons frequently prophylactically release (i.e., incise) fascia of arm and leg fascial compartments after repair of a proximal vascular injury.^{[citation needed]}

Tourniquets

• Pneumatic / Surgical

Pneumatic, surgical tourniquets are frequently applied in the controlled environment of the operating room in order to control blood loss during an upper or lower extremity operative case. Aside from lower blood loss in itself, this improves visualization and surgical efficiency. Modern examples are found in many different sizes to accommodate different patients and sites of applications, with adult cuffs approximately 4″ wide. This distributes the pressure over, generally, a broader area than field (emergency, combat) tourniquets. The cuff is typically attached to an adjustable pneumatic pump with a built-in timer. Surgical tourniquet times in excess of two hours have been associated with an increased risk of nerve damage (e.g.,

Emergency field tourniquets have been used for many centuries, and have seen a resurgence in the recent combat operations in Afghanistan and Iraq, as well as expanded use in civilian trauma and mass casualty settings. Expedient and widespread tourniquet use in the modern combat setting is frequently cited as a primary driver for increased survival following major battlefield trauma. These tourniquets are often 1–2″ in width, which concentrates the pressure to a narrow band of tissue. They can result in tissue necrosis if kept in place for long periods, and should only be applied after other methods to control bleeding (e.g., elevation or direct pressure to the wound) have failed, except in settings where time does not allow waiting. Generally, tissue distal to a field tourniquet that has been in place for greater than 6 hours is considered likely to be non-viable.^[citation needed]

• Tourniquet equivalents

In the same way that external compression tourniquets reduce or eliminate arterial blood flow, aortic cross clamping has the same effect. The resuscitative endovascular balloon occlusion of the aorta (REBOA) device achieves this as well. By design, these devices induce ischemia to the lower extremities (as a secondary effect, or less commonly as their primary use). Releasing the cross clamp or removing the REBOA initiates reperfusion, and IR injury to the lower extremities may follow.^{[citation needed]}

Treatment approaches

Available hind limb IR animal model are either artery vein ligation or tourniquet application (by rubber band or O-ring).^[12][13] Possible treatments are the application of IR related-pathway derived drug/inhibitor and

References