Role of NO in IR‐injury in surgical flaps In free flap surgery, there are two possible secondary ischemia periods, which are not tolerated well.12,13 In the first type, global ischemia occurs to the entire flap because of extra‐ or intraluminal obstruction of the vascular pedicle. This may be arterial or venous or a combination of these. In these cases, secondary ischemia is caused by technical failure of either anastomosis. In the second type, ischemia is prolonged in distal parts of the flap. This can be venous and/or arterial in origin because of variable vascular anatomy and/or excess flap size for its inherent blood supply. The return of blood flow in distal parts of the flap is delayed compared with the central parts of the flap overlying the vascular pedicle following IR. This has been clinically observed in several studies.14,15 This prolonged ischemic period is also called distal ischemia and occurs in the (vascular) margins of the flap. The duration of an ischemia period determines the severity of tissue damage and flap loss.16,17 IR injury may thus occur in whole flaps, but it occurs more commonly in the vascular marginal parts of the flap where the period of ischemia is increased despite reperfusion, rendering this part of the flap more vulnerable to IR injury. Surgical delay of distal parts of the flap is an effective method of reducing partial flap loss and fat necrosis. With surgical delay, the distal random‐pattern blood supply is converted to an axial‐pattern flap by opening the choke vessels.18 This, however, necessitates an extra procedure for the patient. Therefore, a “pharmacological delay” has been the focus of many studies in order to increase the ischemic tolerance of the tissue and reduce IR‐mediated (partial) flap loss. Mechanism of IR Injury Ischemia The tolerance of tissue against ischemia varies, depending on the type of tissue and its metabolic properties. Tissues with higher metabolic rate are more susceptible to ischemia than those with lower metabolic rate (e.g., muscle versus skin). In the early phase of ischemia, adenosine triphosphate (ATP) is provided by glycolysis. As glycogen stores are depleted and the oxygen tissue level drops, cell metabolism is turned to an anaerobic state and causes lactate and other toxic metabolic products. Decreased production of energy‐rich phosphates such as ATP is decreased, and ATP‐dependent processes are halted, leading to cell membrane transport malfunction. This leads to an increase of intracellular calcium, which triggers enzyme‐systems to produce proinflammatory mediators such as interleukins and tumor necrosis factor alpha (TNFα). The released chemical mediators lead to an upregulation of surface adhesion molecules (e.g., P‐selectin, L‐selectin) on endothelial cells, leukocytes, and platelets. At the same time, protective factors from the endothelium, such as NO, are decreased. This results 41
Microsoft Word - chapter 0 v1 DB.doc
To see the actual publication please follow the link above