Role of NO in IR‐injury in surgical flaps Introduction Since the advent of reconstructive surgery, ischemia‐reperfusion (IR) injury has been a detrimental factor in flap viability and survival. Ischemia is a condition of inadequate blood flow, which is an inevitable part in many clinical situations such as free tissue transfers, digit/limb replantation, and organ transplantation. Ischemia is the first level of damage and is characterized by oxygen depletion and conversion of cellular metabolism to anaerobic pathways. In case the ischemia period outruns the tolerance of the tissue, inflammation will develop with cell necrosis. Although reperfusion is essential for flap and tissue survival, reperfusion triggers a cascade of pathophysiological events resulting in tissue injury beyond that caused by the initial ischemia.1 Although success rates greater than 95% are common in microvascular reconstructive procedures, incidental total flap loss and more commonly partial flap loss still occur, frustrating the reconstructive team and increasing the morbidity for the patients. A large volume of experimental data has increased our knowledge of the pathophysiology mechanisms of IR injury. On that basis strategies to avoid flap loss have been investigated. Since the discovery of the endothelium‐derived relaxing factor as nitric oxide (NO) in 1987, a significant volume of research has been published investigating the role of NO in the vascular endothelium and its application to IR injury.2 Using the PubMed search—“Reperfusion Injury” (MesH) and “Nitric Oxide” (MesH)— leads to 1646 published studies. In this paper, the sequence of physiological changes that occur during flap elevation, the mechanisms of IR, and the role and applications of NO in surgical flaps are summarized. NO and NO synthase NO is an important signaling molecule and has a role in neuronal synapse signaling, as a host defense effector in the immune system, as a regulator of vascular tone in the cardiovascular system, and also in reactive oxygen species (ROS) scavenging.3,4 NO and citrulline are produced from L‐arginine and oxygen using nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor by a family of iso‐enzymes termed NO synthase (NOS) (Figure 3.1). Conversely, NO can also pose pathological capacity by forming ROS (peroxynitrate ONOO‐ and OH radicals) and thus contributes to further inflammation.5,6 The two‐faced nature of NO in surgical flaps is such that when presented early in the sequence of inflammatory buildup (e.g., during ischemia or at the start of reperfusion), it reduces/inhibits further inflammation, although its late production by macrophages and neutrophils contributes to the oxidative burst seen in IR. 39
Microsoft Word - chapter 0 v1 DB.doc
To see the actual publication please follow the link above