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Background and Purpose. Microamperage direct current and microamperage electromagnetic stimulation are used to accelerate healing in bone. Although many clinicians are using microamperage stimulation to relieve pain and facilitate wound healing, there is significant question regarding whether this low-intensity direct current significantly accelerates soft tissue wound repair. The purpose of this study was to determine whether low-voltage pulsed microamperage current (100 μA, 60 V, 0.1 Hz) enhances the healing of superficial, full-thickness, or incisional wounds created to simulate acute abrasions, ulcers, and lacerations. Subjects. Ten adult Yucatan mini pigs served as the subjects for this study. Methods. Variables associated with healing were measured in 60 matched pairs of surgically induced partial-thickness, full-thickness, and incisional wounds after either sham or anodal (positive-polarity) stimulation with pulsed microamperage current (100 μA) was administered for 1 hour per day for 5 days. Sterile, disposable electrodes (2×4 cm) were placed over each wound, which was kept wrapped and protected throughout the study. Results. At 7 days postinjury, all wounds were healing well with no signs of infection. There were no differences in tensile strength, collagen density, maturity, or deposition (hydroxyproline), wound size, or visual appearance between the sham treatment and treatment lesions. No changes in local subcutaneous oxygen or temperature were found in the swine during or after microamperage stimulation. Conclusion and Discussion. This study did not provide any evidence to support the use of microamperage stimulation to accelerate wound healing. No negative effects, however, were found. Further research is needed to determine whether there is a critical interaction between the size of the electrode relative to the wound, the density of the current, the duration of the treatment, the polarity of the treatment electrode, and the acuity or chronicity of wounding and the effectiveness of microcurrent stimulation for wound healing.

Oxygen tension and collagen deposition were measured in standardized, subcutaneous wounds in 33 postoperative surgical patients. Pertinent clinical and wound parameters were analyzed by Pearson's correlation test and sequential linear regression analysis. Collagen deposition was directly and significantly proportional to wound oxygen tension and measures of perfusion. There were no significant correlations with hematocrit, estimated blood loss, length of operation, smoking, age, weight, sex, or urine output. This study in humans confirms animal experiments showing that collagen deposition and tensile strength in wounds are limited by perfusion and tissue oxygen tension. It appears unnecessary to maintain hemoglobin at normal levels to support repair, provided that peripheral perfusion can be maintained at a high level in compensation for anemia. These circumstances reflect the fact that although oxygen is essential to many aspects of healing, and must be delivered at adequate partial pressures, reparative tissue consumes relatively little of it.

Hypothesis Anti-inflammatory corticosteroids significantly impair wound healing. Retinoids partially, but significantly, reverse this effect. Little is known about the mechanism of steroid retardation or retinoid reversal. We hypothesized that corticosteroids lower transforming growth factor-β (TGF-β) and insulin-like growth factor-I (IGF-I) levels and tissue deposition in wounds and that retinoids stimulate corticosteroid-impaired TGF-β and IGF-I release and collagen production. Design Randomized controlled trial. Setting Wound healing research laboratory. Participants Animal study. Interventions Four wire mesh wound cylinders were implanted subcutaneously into the backs of 72 male Sprague-Dawley rats. Wound healing was impaired by a single subcutaneous injection of 6 mg of methylprednisolone acetate (Depo-Medrol). Two preparations of retinoids were used in separate experiments: all- trans -retinoic acid and 9- cis -retinoic acid that were fed orally. Main Outcome Measures Hydroxyproline content was measured in the healing tissue and TGF-β and IGF-I levels were analyzed in the wound fluid. Results Methylprednisolone treatment significantly decreased TGF-β and IGF-I levels in the wound fluid and hydroxyproline content in the tissue ( P trans - and 9- cis -retinoic acid partially reversed the TGF-β and IGF-I decrease and significantly increased hydroxyproline content toward normal levels ( P trans -retinoic acid enhanced collagen deposition, TGF-β and IGF-I levels over normal chow fed control animals ( P Conclusions Steroids and retinoids have antagonistic effects on growth factors and collagen deposition in wound healing. These effects can be relevant for treatment options in a clinical setting.

Background: "Respiratory burst" activity, ie, O 2 −production, is dependent on Po 2 , temperature, pH, and glucose concentrations within the physiologic range. Objectives: To determine whether environmental conditions characteristic of wounds may limit human neutrophil respiratory burst metabolism and to clarify the degree to which bactericidal oxidant production depends on local Po 2 . Methods: Human blood and wound neutrophils were stimulated with phorbol myristate acetate. Oxygen consumption and superoxide production were measured over a range of 30 to 300 mm Hg Po 2 , 0 to 40 mmol/L glucose, pH 6.0 to 8.0, and 30°C to 37°C. The apparent Michaelis Menten constant for oxidant production with respect to Po 2 was calculated. Results: Oxygen consumption and O 2 −production were dependent on Po 2 throughout the range tested. Half-maximal oxidant production occurred in the range of 45 to 80 mm Hg Po 2 and maximal at Po 2 higher than 300 mm Hg. These data agree with the highest previous estimates. Oxidant generation was also dependent on pH, temperature, and glucose concentration, but to a lesser extent. Conclusions: Leukocyte bacterial killing capacity as measured by oxygen consumption and superoxide production are substantially impaired at the low oxygen tensions often found in wounds. Changes in pH, temperature, and glucose concentration have lesser but nonetheless significant consequences. The data provide a plausible mechanism for the vulnerability of some wounds to infection and for the previous finding that increasing oxygen tension at wound sites enhances bactericidal function. Thus, the data serve as a basis for future studies on prevention of wound infection. Arch Surg. 1997; 132:991-996

Hypothesis Women deposit more collagen after major abdominal surgery than men. Design A post hoc analysis of data obtained from 2 prospective, randomized, double-blind clinical trials. Setting University hospital general surgical service. Patients One hundred sixteen patients undergoing colon resection. Main Outcome Measures Protein and hydroxyproline (collagen) deposition during the first 7 postoperative days in expanded polytetrafluoroethylene implants positioned subcutaneously. Results On univariate analysis, men and women deposited comparable amounts of collagen (257 ± 120 vs 281 ± 117 ng/mm, respectively). When potential confounding factors were entered into a generalized mixed-effects model, only the interaction between age and sex was a significant factor ( P = .047). Collagen deposition decreased with age in men, being 317 ± 133 ng/mm in men younger than 45 years, but only 238 ± 113 ng/mm in those older than 45 years ( P = .03). In contrast, collagen deposition was virtually identical in women younger than 45 years (280 ± 133 ng/mm) and in those older than 45 years (281 ± 110 ng/mm). Only 3 of these women were receiving hormone replacement therapy. Conclusions Collagen deposition after surgery decreased significantly with age in men, while remaining unchanged in women. Younger men and women deposited similar amounts of collagen. Therefore, older men made less collagen after surgery than older women, perhaps explaining the consistent observation that wound dehiscence is twice as common in men than in women. Our results differ from previous studies conducted in healthy, nonsurgical volunteers, which showed that (1) young women made significantly more collagen than young men and (2) collagen deposition was reduced in postmenopausal women, but deposition returned to premenopausal values with hormone replacement therapy. Differences between our results and those reported previously likely stem from the populations studied. In particular, multiple perioperative factors decrease collagen deposition, which apparently obscures the differences observed previously in healthy, unstressed volunteers.