Paul N. Manson

Xanthine: Acceptor oxidoreductase activities in ischemic rat skin flaps

Xanthine:acceptor oxidoreductase activities were assayed in free skin flaps following prolonged preservation. In normal rat skin, xanthine dehydrogenase transfers electrons to NAD+ and accounts for 73% of total oxidoreductase activity, and xanthine oxidase transfers electrons to molecular oxygen and accounts for the remaining 27%. Xanthine oxidase activity increased significantly in skin flaps during ischemia: approximately 30 and 100% increases after 6 and 24 hr of ischemia, respectively. Allopurinol inhibited xanthine oxidoreductase activity: free skin flaps obtained from allopurinol-treated animals exhibited a low level of xanthine oxidoreductase activity throughout the period of preservation. Systemic allopurinol significantly improved the survival rate from 32 to 75% of free flaps transferred after 24 hr of preservation at room temperature. These observations suggest that the xanthine oxidase system is a major source of oxygen free radicals following ischemia/reperfusion in skin. The increase in xanthine oxidase is attributable to the conversion of xanthine dehydrogenase to oxidase, a conversion which involves sulfhydryl oxidation in skin flaps.

Biologic response to passive dissolution of titanium craniofacial microplates

The effect of anodization on passive dissolution of titanium was studied by measuring titanium levels in peritoneal leukocytes and tissues of laboratory animals with titanium plates implanted into the peritoneal cavity. Fifteen Sprague-Dawley rats were assigned randomly to three treatment groups of five animals. One group served as controls, the other two groups had an anodized or an unanodized implant placed in the left paracolic gutter. Peritoneal lavage samples and blood samples, organ tissues and tissue surrounding the implants, were removed for histologic examination and titanium levels. Titanium was not detected in any distant organs or in the peritoneal lavage fluid. The capsular tissues surrounding the implants contained titanium at levels ranging from 2610 to 16786 ng/g for unanodized plates, and 888-5933 ng/g for anodized plates. The titanium levels within the peritoneal leukocytes of animals with unanodized implants were significantly elevated (P = 0.01) over time, as compared with controls. The level of titanium in the peritoneal leukocytes of animals with anodized implants was not significantly elevated when compared with controls. Titanium levels in the trace range, as measured in the capsular tissues, are likely a result of corrosion. Surface treatment of titanium by anodization reduces passive dissolution.

The role of metal ions in ischemia/reperfusion injury in skin flaps

The role of hydroxyl radical generation by the metal-catalyzed Haber-Weiss reaction in producing injury to postischemic skin flaps in rats was evaluated. The venous drainage from groin island flaps was occluded for 7 hr and then reperfused. The flaps were infused with either deferoxamine, CaNa2EDTA, histidine, salicylate, or vehicle (saline) at the time of reperfusion. In another experimental group, the role of hydrogen peroxide was evaluated by the infusion of catalase at the time of reperfusion. Treatment with a single dose of deferoxamine (40 mg/kg), CaNa2EDTA (50 mg/kg), or histidine (50 mg/kg), significantly increased the flap survival rate from 24 to 63, 75, and 63%, respectively. A large dose of salicylate (80 mg/kg) improved the flap survival rate (to 63%): a smaller dose (40 mg/kg) offered no improvement. A large dose of catalase ameliorated the survival rate (to 88%). The results suggest that the presence of metal ions is required for the expression of free radical-induced tissue damage. Hydrogen peroxide appears to be essential for the production of this injury.

Flap tolerance to ischaemia in streptozotocin-induced diabetes mellitus

The effects of diabetes mellitus (DM) on skin flap tolerance to 3 h of secondary venous ischaemia were evaluated. Epigastric island flaps were elevated 3, 6 and 12 weeks after induction of DM in rats. In the non-diabetic control groups, the flap survival was 85% in the 3-week group, 72% in the 6-week, and 78% in the 12-week. In untreated DM groups, the flap survival significantly decreased to 40% in the 3-week group, 25% in the 6-week, and 17% in the 12-week (P < 0.05 in all groups). Flap survival in the DM/insulin group decreased to 31% in the 3-week group. Effects of insulin therapy, however, were observed in later stages of DM: 71% and 62% survival in the 6- and 12-week group, respectively. Significant linear correlations between enzymatic responses and the flap survival were found. The results suggest that DM is detrimental to flap tolerance and is associated with the lack of metabolic responses to secondary ischaemia.

Forehead reconstruction with microvascular flaps: utility of aesthetic subunits.

BACKGROUNDnCurrent literature describes the forehead as one aesthetic subunit of the face. We argue for the usefulness of aesthetic forehead subunits when microvascular flap reconstruction is required. Key to utilization of microvascular flaps for restoration of forehead subunits is an understanding of the patient population and defect characteristics most amiable to treatment.nnnMETHODSnWe conducted an International Review Board-approved retrospective chart review of nine consecutive patients who had undergone free flap reconstruction for large forehead defects.nnnRESULTSnThe patients foreheads included one paramedian defect; one central and paramedian defect; four central, paramedian, and lateral defects; and three lateral defects. Seven patients had ulnar forearm flaps and two had anterolateral thigh flaps. The success rate was 100%.nnnCONCLUSIONnA forehead subunit classification system has been devised that provides a suitable option for cases that benefit from distant tissue replacement in a single stage, while preserving the principles of aesthetic replacement.

The effect of cobalt chloride on skin flap survival

The effects of cobalt chloride on ischaemia-reperfusion injury were evaluated in skin flaps. Groin neurovascular island flaps, 3 x 6 cm, were elevated in rats and subjected to primary and secondary ischaemia. Primary ischaemia was produced by 1 hour occlusion of the femoral artery and vein and, 22 hours later, secondary ischaemia was produced by 3 hours venous occlusion. The treatment group received intraperitoneal cobalt chloride (5 or 10 mg/kg) at the time of secondary ischaemia. Flap survival was 80% in the control, 10 to 20% in the cobalt chloride treated, and 20% in the cobalt plus mannitol group. Mannitol (100 mg/kg) failed to prevent the harmful effects of cobalt. Skin flaps exposed to cobalt chloride exhibited increased thiobarbituric acid reactant (TBAR) levels of 20 to 30 times normal. Of the antioxidant enzymes, glutathione peroxidase activity increased by 40% (P < 0.01), whereas glutathione reductase activity decreased by 40% (P < 0.01) in the cobalt exposed groups. Glucose 6-phosphate dehydrogenase activity was not affected.

Intraoperative Use of Vasopressors Is Safe in Head and Neck Free Tissue Transfer.

BACKGROUNDnThe purpose of this study is to identify whether intraoperative use of vasoactive medications increases the risk of free flap failure or complications through a systematic review and meta-analysis.nnnMATERIALS AND METHODSnPubMed/MEDLINE, EMBASE, and Scopus databases were searched for studies published through January 2015. English publications that met the following criteria were included: (1) adult patients undergoing head and neck free flap reconstruction; (2) comparison of patients with and without intraoperative vasopressor administration; and (3) documentation of flap failure rate and/or flap complications. The primary outcome was the incidence of flap failure. The secondary outcome was the incidence of overall flap complications. Meta-analysis was performed to obtain pooled odds ratios (ORs) of the effect of intraoperative use of vasopressors on flap failure and complication rates.nnnRESULTSnFour cohort studies met inclusion criteria. All studies were of high methodological quality with an average Methodological Index for Non-Randomized Studies score of 18.75 (range 16-23). A total of 933 patients undergoing head and neck free flap reconstruction were included. Meta-analysis demonstrated no statistically significant difference in the incidence of flap failure (2.9 vs. 3.6%; OR, 0.68; 95% confidence interval [CI], 0.23-1.99; pu2009=u20090.48) or incidence of flap complications (16.8 vs. 18.6%; OR, 0.92; 95% CI, 0.60-1.42; pu2009=u20090.71).nnnCONCLUSIONnBased on the current evidence, intraoperative use of vasopressors has no impact on the incidence of flap failure or flap complications.

The safety and efficacy of epinephrine in hand surgery: a systematic review of the literature and international survey

The concept that epinephrine-based local anesthetics cannot be injected in terminal appendages has been perpetuated for decades. The hypothesis that the vasoconstrictive effect of epinephrine will result in finger necrosis has been accepted as fact, often preventing its use in hand surgery. To scientifically challenge this hypothesis, a systematic review of the literature was performed, and a survey of ASPS members reported to highlight the lack of evidence-based opinions. A systematic literature review performed using Medline, Embase, PubMed, and Cochrane databases identified all published studies evaluating use of epinephrine/adrenaline in hand, finger or digit surgery. Each study was independently evaluated by three reviewers for inclusion or exclusion from the systematic review. Additionally, a survey (E-survey link) was distributed to all ASPS members and data were collected over a 5-month period through SurveyMonkey®. A total of 568 articles published prior to December 2012 were identified. After elimination of 151 duplicates, 417 articles remained. Fifty-five articles were selected and full examination of the texts was performed. Forty-five studies matched the selection criteria and were included in the analysis. The ASPS member survey demonstrated a 13xa0% overall questionnaire response rate (5,299 questionnaires/687 responses). Of all respondents, 37.4xa0% felt it was unsafe to inject local anesthesia mixed with epinephrine into the fingers/thumb, respectively. Critical literature review validated the safety and efficacy of utilizing epinephrine-based local anesthetics. The author’s survey elucidates the pervasive concern of employing epinephrine in hand surgery.Level of Evidence: Not ratable

Application of the Mandible Injury Severity Score to Pediatric Mandibular Fractures

PURPOSEnThe Mandible Injury Severity Score (MISS) has been used to evaluate adult mandibular fractures. The purpose of this study was to evaluate the MISS in a cohort of pediatric patients.nnnPATIENTS AND METHODSnThis was a retrospective study of pediatric patients treated for mandibular fractures over a 20-year period. Patients were included if they had computed tomographic imaging available for review and had at least 1 post-treatment visit. The primary predictor variable was the MISS. Secondary predictors were demographic and injury-associated factors. The outcome was treatment-associated complications. Descriptive, bivariate, and multiple logistic regression statistics were computed.nnnRESULTSnOne hundred sixteen patients with mandibular fractures were identified; 73 (62.9%) met the inclusion criteria. The samples mean age was 8.5 ± 4.1 years; 44% were girls. Motor vehicle collisions (60%) and falls (15.1%) were the most common mechanisms. More than 50% of patients had an extra-mandibular injury. The mean MISS was 13.5 ± 7.8. Forty-five percent of the sample underwent open reduction and internal fixation. Complications were noted in 20.5% of patients, of which malocclusion was the most common (8.2%). Increasing MISS was associated with complications (P < .001). After controlling for the effects of age, mechanism, cervical spine and skull base injuries, and treatment, patients with an MISS of at least 14 were significantly more likely to have a complication (odds ratio = 4.0; 95% confidence interval, 1.05-15.0; P = .04).nnnCONCLUSIONSnIn pediatric patients with mandibular fractures, increased severity of injury is associated with complications, even after controlling for the effects of multiple confounders, including open treatment.

Microanalyses of enzymes and metabolites in ischemia/reperfusion‐induced partial‐thickness skin wounds

A transition zone between well‐perfused proximal tissue and inadequately perfused distal tissue was evaluated histologically and biochemically in skin flaps. Cranially based pedicle flaps, 3 × 7.5 cm, were made on the backs of female Sprague‐Dawley rats. Flap survival was 22% of the original flap area at 7 days and 40% at 14 days after flap elevation (p < 0.001). The transition zone consisted of full‐thickness skin survival proximally and partial‐thickness wound distally. It is evident that skin wounds induced by ischemia or reperfusion repair continuously between 7 and 14 days after flap elevation. Tissue glucose, lactate, and hypoxanthine levels were measured to assess capillary perfusion in the transition zone on postoperative day 3. The proximal full‐thickness skin 5 mm from the wound margin demonstrated no significant changes in glucose and lactate levels compared with normal skin. The partial‐thickness wounds exhibited no change in glucose (a 33% decrease was not statistically significant) but a significant increase (319% of normal) in lactate level (p < 0.05). Hypoxanthine levels increased to 453% of normal in full‐thickness skin (p < 0.01) and to 787% in partial‐thickness wounds (p < 0.001). Metabolic response was evaluated by enzyme assays in the transition zone. Hexokinase activity increased by 251% of normal (p < 0.05), glucose 6‐phosphate dehydrogenase by 245% (p < 0.01), and glutathione reductase by 184% (p < 0.05) in the proximal full‐thickness skin. Hexokinase activity further increased by 482% of normal (p < 0.01), glucose 6‐phosphate dehydrogenase by 379% (p < 0.05), and glutathione reductase by 346% (p < 0.01) in partial‐thickness wounds. The results suggest that partial‐thickness wounds have less capillary circulation but greater antioxidant enzyme activities than does the survival area with full‐thickness skin.