Cath Lab Digest

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     Wound healing is influenced by a combination of well-documented environmental and biological factors that have an impact on patient recovery. Currently, no effective diagnostic tools to assess the critical biologic activities or impairments within the wound that, in turn, may direct clinicians to the most appropriate and cost effective wound treatment protocols exist — treatment protocols designed to address wound healing range in effectiveness and are not based on the biologic activity of each unique wound. In many cases, wound care practitioners feel as if they are flipping a coin when selecting wound therapies. Many times, the trial-and-error processes used for clinical wound management lead to significant expense and prolong patient morbidity.

     If clinicians were able to assess the biological factors affecting the wound, they would have a clearer concept of what constitutes appropriate therapy. One way to do this is to use biomarkers of wound healing to assess the state of readiness of a wound for healing. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological or biochemical features that can be used to assess the progress of disease or the effects of treatment. Currently, approximately 14 known biomarkers are under investigation for use as either a diagnostic tool or therapy for the treatment of chronic or difficult-to-heal wounds.

     In the effective treatment of wounds, diagnostic tests utilizing biomarkers would be used to predict and manage wound outcomes and would play a critical role in determining the cause of a wound, assessing its status in healing and helping identify any comorbidities or complications that may contribute to healing delay. These tests also would be helpful in the development of effective management plans using proven wound protocols.

     Nitric oxide. One biomarker being investigated as a diagnostic test for wound healing is nitric oxide (NO). Nitric oxide is formed from the amino acid L-arginine and oxygen by three distinct isoforms of nitric oxide synthase (NOS). The inducible isoform (iNOS) is synthesized in the early phase of wound healing by inflammatory cells (mainly macrophages) and is a critical co-factor in wound healing.¹ NO is a pivotal biological factor for wound repair and is an important regulator of wound inflammation, epidermal cell migration, wound angiogenesis, collagen deposition, and wound tensile strength. The stable, end-oxidation products of NO (called nitrate, or NOx) can be measured in tissues and fluids to determine NO bioactivity in wounds. The early results of these determinations in clinical settings appear to offer promise for the use of NO as a noninvasive diagnostic indicator of wound healing.^2-4

     A current hypothesis regarding the role of NO assumes that when wound NO bioactivity is significantly below normal biological levels for wounds — or the optimal range that promotes healing — normal wound repair mechanisms are impaired. Therefore, by measuring wound NO bioactivity (using NOx), we may be able to predict wound outcomes for difficult-to-heal wounds, monitor the effectiveness of selected “wound healing” therapies, and develop “novel” topical wound treatments or dressings based on their ability to enhance wound NO bioactivity.

     Matrix metalloproteinase. Another biomarker that, like NO, plays a critical role in the healing process is matrix metalloproteinase (MMP).