Homocysteine– A Stealth Mediator of Impaired Wound Healing: A Preliminary Study

  • 4/1/2006
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Author(s): 
Joseph V. Boykin, Jr., MD,1,2 and Chris Baylis, PhD3

Howdieshell31 documented a pattern of wound fluid NOx enhancement associated with a normal wound healing response that is similar to that observed with the responding dermal substitute patient. Using an experimental porcine ventral hernia wound model, Howdieshell measured wound fluid NOx, wound vascular perfusion and VEGF, and transforming growth factor-b (TGF-b) expression during normal wound repair and following the inhibition of iNOS. In this study, the maximal elevation of wound fluid NOx occurred on Day 11 of the study and was preceded by increased basal and heat provoked wound perfusion and increased thickness of healthy granulation tissue. This maximal elevation in wound fluid NOx was significantly greater than pre-injury values and correlated with significant elevations in the concentrations of VEGF and TGF-β from the granulating wound surface. After pharmacologic inhibition of iNOS, a significant reduction in wound NO bioactivity and wound fluid NOx was associated with decreased granulation tissue formation, VEGF expression, and impaired wound healing. Despite the limited clinical observations made in the present study, the authors believe that the supernormal elevations in wound fluid NOx associated with a normal wound healing response observed by Howdieshell are supportive of the present clinical findings. The present findings have demonstrated similar patterns of maximally increased wound fluid NOx (at about 2 weeks) that were associated with a favorable response for wound closure. Furthermore, given the identification of a normal wound fluid NOx threshold for normal healing established from the authors’ center, these observations suggest that baseline wound fluid NOx determinations may be predictive of successful outcome for the patient receiving dermal substitute treatment.
Homocysteine is an intermediate sulfur-containing amino acid formed during the intracellular metabolism of methionine, an essential amino acid supplied by dietary proteins.17 The factors responsible for hyperhomocysteinemia include inborn errors of homocysteine metabolism, drugs that interfere with homocysteine metabolism, deficiencies of folic acid, vitamin B6 (pyridoxal 5’-phosphate) or vitamin B12 (methylcobalamin), and certain disease states, such as chronic renal failure, that increase total plasma homocysteine levels.17 The prevalence of hyperhomocysteinemia for the general population and for individuals with metabolic syndrome or type II diabetes mellitus is estimated between 5% and 7%.32 These figures underscore the significance of the documented incidence of elevated Hcy in the authors’ chronic wound population where 50% of these patients and 63% of patients with diabetes mellitus and neuropathic LEU were observed with untreated, elevated Hcy levels.

References: 

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