Optimization and validation of an ischemic wound model

Localized tissue ischemia is a key factor in the development and poor prognosis of chronic wounds. Currently, there are no standardized animal models that provide sufficient tissue to evaluate the effect of modalities that may induce angiogenesis, and in vitro models of angiogenesis do not mimic the complexity of the ischemic wound bed. Therefore, we set out to develop a reproducible ischemic model for use in wound-healing studies. Male Sprague-Dawley rats underwent creation of dorsal bipedicle skin flaps with centrally located excisional wounds. Oxygen tension, wound-breaking strength, wound area, lactate, and wound vascular endothelial growth factor (VEGF) were compared in flaps measuring 2.5 and 2.0 x 11 cm with and without an underlying silicone sheet. We found that the center of the 2.0 cm flap with silicone remains in the critically ischemic range up to 14 days without tissue necrosis (33+/-4 vs. 49+/-6 mmHg in controls). Wound healing and breaking strength were significantly impaired and tissue lactate from the center of this flap was 2.9 times greater than tissue from either nonischemic controls and 2.5 cm flap (0.23+/-0.05 mg/dL/mg sample vs. 0.09+/-0.02 and 0.08+/-0.02, respectively). Vascular endothelial growth factor was 2 times greater than the nonischemic control. This ischemic wound model is relatively inexpensive, easy to perform, reproducible, and reliable. The excisional wounds provide sufficient tissue for biochemical and histologic analysis, and are amenable to the evaluation of topical and systemic therapies that may induce angiogenesis or improve wound healing.     

Hyperbaric oxygen delays healing in an ischemic wound model

The true etiology of non-healing, chronic wounds remains elusive. One common denominator, whether the wounds are due to pressure, diabetes, or arterial insufficiency is localized tissue ischemia in the wound bed. Angiogenesis is an important process in tissue growth and development and therefore plays an integral role in wound healing. This study was designed to test the hypothesis that hyperbaric oxygen (HBO) will promote angiogenesis and therefore improve healing in a rat model of tissue ischemia. A rat model of tissue ischemia was used in which excisional wounds were centered on a 2.0 cm dorsal bipedicle skin flap with an intervening silicone sheet. In previous studies we have shown that the tissue remains ischemic up to 14 days, wound healing and tensile strength are impaired and lactate is elevated. After flap creation, 60 rats were divided into treatment and control groups, with the treatment group receiving daily HBO at 2.4 atm for 90 minutes. Wound surface area tracing and excision of the wound beds was performed on days 1, 3, 7, 10 and 14, with n = 6 per data point. The concentration of VEGF in wound extracts was quantified by ELISA and standardized for total protein. Data were expressed as mean ± SEM. The wound healing curves diverge at day 5, with HBO-treated wounds consistently larger and delayed in healing compared to control (day 7: HBO - 0.27 ± 0.02 cm² vs control - 0.17 ± 0.07 cm², day 14: HBO - 0.06 ± 0.04 vs cm² vs control - 0.03 ± 0.02 cm²). VEGF is greater at all time points in the control wounds with a peak at day 10 (HBO: 159 ± 55 pg/mg protein vs control: 244 ± 61 pg/mg protein). Non-ischemic wounds expressed low levels of VEGF, which was unchanged by hyperbaric treatment throughout the course of healing. HBO suppresses the expression of VEGF and delays healing in a model of tissue ischemia. Ongoing studies will analyze the effect of HBO on matrix metalloproteinase expression and the relationship between the angiogenic factors, oxidative stress and neovascularization.     

Electron paramagnetic resonance assessment of brain tissue oxygen tension in anesthetized rats

The adequacy of cerebral tissue oxygenation (PtO(2)) is a central therapeutic end point in critically ill and anesthetized patients. Clinically, PtO(2) is currently measured indirectly, based on measurements of cerebrovascular oxygenation using near infrared spectroscopy and experimentally, using positron emission tomographic scanning. Recent developments in electron paramagnetic resonance (EPR) oximetry facilitate accurate, sensitive, and repeated measurements of PtO(2). EPR is similar to nuclear magnetic resonance but detects paramagnetic species. Because these species are not abundant in brain (or other tissues) in vivo, oxygen-responsive paramagnetic lithium phthalocyanine crystals implanted into the cerebral cortex are used for the measurement of oxygen. The line widths of the EPR spectra of these materials are linear functions of PtO(2). We used EPR oximetry in anesthetized rats to study the patterns of PtO(2) during exposure to various inhaled and injected general anesthetics and to varying levels of inspired oxygen. Rats anesthetized with 2.0 minimum alveolar anesthetic concentration isoflurane maintained the largest PtO(2) (38.0 +/- 4.5 mm Hg) and rats anesthetized with ketamine/xylazine had the smallest PtO(2) (3.5 +/- 0.3 mm Hg) at a fraction of inspired oxygen (FIO(2)) of 0.21, P < 0.05. The maximal PtO(2) achieved under ketamine/xylazine anesthesia with FIO(2) of 1.0 was 8.8 +/- 0.3 mm Hg, whereas PtO(2) measured during isoflurane anesthesia with FIO(2) of 1.0 was 56.3 +/- 1.7 mm Hg (P < 0.05). These data highlight the experimental utility of EPR in measuring PtO(2) during anesthesia and serve as a foundation for further study of PtO(2) in response to physiologic perturbations and therapeutic interventions directed at preventing cerebral ischemia. IMPLICATIONS: Using in vivo electron paramagnetic resonance oximetry, we studied the patterns of cerebral tissue oxygenation (PtO(2)) during exposure to various inhaled and injected general anesthetics, and to varying levels of inspired oxygen. These data show that inhaled anesthetics result in larger levels of PtO(2) in the brain than do several injectable anesthetics. The results highlight the experimental utility of electron paramagnetic resonance in measuring PtO(2) during anesthesia and serve as a foundation for further study of PtO(2) in response to physiologic perturbations and therapeutic interventions directed at preventing cerebral ischemia.     

Wound healing essentials: Let there be oxygen

The state of wound oxygenation is a key determinant of healing outcomes. From a diagnostic standpoint, measurements of wound oxygenation are commonly used to guide treatment planning such as amputation decision. In preventive applications, optimizing wound perfusion and providing supplemental O₂ in the perioperative period reduces the incidence of postoperative infections. Correction of wound p O₂ may, by itself, trigger some healing responses. Importantly, approaches to correct wound p O₂ favorably influence outcomes of other therapies such as responsiveness to growth factors and acceptance of grafts. Chronic ischemic wounds are essentially hypoxic. Primarily based on the tumor literature, hypoxia is generally viewed as being angiogenic. This is true with the condition that hypoxia be acute and mild to modest in magnitude. Extreme near-anoxic hypoxia, as commonly noted in problem wounds, is not compatible with tissue repair. Adequate wound tissue oxygenation is required but may not be sufficient to favorably influence healing outcomes. Success in wound care may be improved by a personalized health care approach. The key lies in our ability to specifically identify the key limitations of a given wound and in developing a multifaceted strategy to specifically address those limitations. In considering approaches to oxygenate the wound tissue it is important to recognize that both too little as well as too much may impede the healing process. Oxygen dosing based on the specific need of a wound therefore seems prudent. Therapeutic approaches targeting the oxygen sensing and redox signaling pathways are promising.     

Oxygen in Wound Healing and Infection

It is a fundamental clinical observation that wounds do not heal in tissue that does not bleed, and they almost always heal in tissue that bleeds extensively. Continuous supply of oxygen to the tissue through microcirculation is vital for the healing process and for resistance to infection. Evaluation of tissue perfusion and oxygenation is important in all types of wound patients. Monitoring systems should measure the hemodynamic situation and the ability of the cardiovascular system to deliver an adequate volume of oxygen to meet the metabolic demands of the peripheral tissue. Oxygen therapy is important in relation to both healing and resistance to infections. External factors have been shown to significantly decrease the peripheral oxygen supply, and supplementary perioperative oxygen to reduce the surgical wound infection rate by one- half in patients undergoing colorectal resection. Hyperbaric oxygen therapy may be beneficial in situations where the nutritive flow and oxygen supply to the healing tissue are compromised by local injury, and particularly if anaerobic infection is present. However, the definitive proof for the effect and indications of this therapy in wound healing still has to be established. It can be concluded that adequate delivery of oxygen to the wound tissue is vital for optimal healing and resistance to infection. Assessment of perfusion and oxygenation is essential for the wound patient, as well as the treating personnel. The indication for hyperbaric oxygen treatment still needs to be defined. During wound healing the continuity and function of the damaged tissue are re-established. This is only possible through a restoration of the microcirculation and thereby the nutrition to the tissue. The main component of the nutrition is oxygen, which is critically important for healing a wound by production of granulation tissue and for ensuring resistance against infection. This has been shown experimentally, but recently a short period of supplementary oxygen has been shown to decrease wound complications in clinical practice as well.     

Topical oxygen therapy & micro/nanobubbles: a new modality for tissue oxygen delivery

Up to 15 billion dollars of US health care expenditure each year is consumed by treatment of poorly healing wounds whose etiologies are often associated with aberrancies in tissue oxygenation. To address this issue, several modes of tissue oxygen delivery systems exist, including Hyperbaric Oxygen Therapy (HBOT) and Topical Oxygen Therapy (TOT), but their efficacies have yet to be fully substantiated. Micro/nanobubbles (MNBs), which range anywhere from 100 μm to <1 μm in diameter and are relatively stable for hours, offer a new mode of oxygen delivery to wounds. The aim of this article is to systematically review literature examining the use of TOT for wound healing and use of MNBs for tissue oxygenation using the MEDLINE database. The search yielded 87 articles (12 MNB articles and 75 TOT articles), of which 52 met the inclusion criteria for this literature review (12 MNB articles and 40 TOT articles). Additionally, we present an analysis on the efficacy of our MNB generating technology and propose its use as a wound healing agent.     

Altered collagen metabolism and delayed healing in a novel model of ischemic wounds

Cellular mechanisms occurring in the healing wound have been well described in various animal models. However, the events associated with wound healing seen in ischemic skin have not been as thoroughly defined. In this series of experiments, we created a novel model of excisional skin wounds under gradient ischemia to study the cellular and extracellular events leading to delayed healing. We hypothesized that altered collagen metabolism accounts for delayed wound healing in ischemic skin. Three pairs of 4 mm punch wounds were made 4 days after bipedicle skin flaps were created on the dorsum of rats. Sham-operated control animals had the same punch wounds without flap creation. The kinetics of excisional wound healing were measured by means of computerized planimetry. In addition, wounds were excised with a 6 mm trephine, radiolabelled with ((3)H)-proline and in vitro collagen synthesis determined as collagenase digestible protein along with quantitation of DNA content. Total collagen deposition was determined as 4-hydroxy-L-proline by high-performance liquid chromatography, and wounds were histologically evaluated. Data was analyzed by means of two-way analysis of variance. Although control wounds healed by day 10, flap wounds consistently had greater surface area on days 2, 4, 6, 8, and 12 (p < 0.001). Relative collagen synthesis (% collagen/noncollagen protein), as measured by an in vitro synthesis method, showed no statistically significant differences between flap and controls wounds. However, the total collagen content (deposition) as measured by 4-hydroxy-l-proline was significantly lower in flap wounds compared with controls on days 7 (p < 0.05) and 9 (p < 0.001). In addition, a significant increase occurred in DNA content in the flap wounds on days 7 (p < 0.05) and 9 (p < 0.001) versus control wounds. These data indicate that, in ischemic wounds, significantly less collagen is deposited despite the inherent ability of the tissue to synthesize appropriate levels of collagen. Because the in vitro collagen synthesis technique only assesses the ability of the tissue to synthesize collagen in a well oxygenated environment, one cannot be assured that the tissue expresses this potential in vivo. However, these data are consistent with the hypothesis that the delay in wound closure is due to an alteration in collagen metabolism which results in a net decrease in collagen accumulation. Because of the observed increase in DNA within the ischemic wounds, we suggest that there is prolonged inflammation in these wounds which may enhance collagen degradation through the release of proteases. In addition, there may be an inability of the tissue to maintain appropriate levels of collagen in this inflammatory wound environment.     

封闭负压技术治疗各种术后伤口裂开

目的：观察封闭负压技术治疗外科手术后伤口裂开的临床效果及总结应用经验。方法：从2007年5月至2009年12月,采用封闭负压技术治疗各类外科术后伤口裂开患者17例,其中男10例,女7例,平均年龄41岁。创面面积为0.5cm×3.2cm～5.5cm×18.6cm,创面形成时间为8～94天,期间采用常规湿敷或中药换药治疗伤口未愈。给予-120mmHg～-150mmHg负压持续吸引,治疗时间为6～37天。结果：10例经封闭负压治疗后创面直接愈合,其余7例创面清洁,肉芽组织新鲜,伤口缩小,4例清创缝合,2例行局部皮瓣转移,1例行皮片移植修复,伤口均一期愈合。术后随访2～12个月,所有伤口愈合良好,无再次裂开。结论：封闭负压技术简便、无创,能有效促进伤口清洁,加快肉芽组织生长,缩短创面愈合时间,适合治疗各种外科术后伤口裂开,有较高的临床推广应用价值。     

Thrombin peptide TP508 accelerates closure of dermal excisions in animal tissue with surgically induced ischemia.

TP508 is a synthetic peptide corresponding to amino acids 508 through 530 of human prothrombin. We previously demonstrated that a single topical application of TP508 stimulates revascularization and healing of acute incisional and excisional wounds in normal, healthy rat skin. To determine if TP508 would enhance wound healing in ischemic skin, we used bipedicle flaps, cranially based flaps, and free grafts to surgically create ischemic regions on the backs of rats. Full-thickness, circular excisions were made within the flaps or grafts and immediately treated with a single application of saline +/- TP508 (0.1 microg/wound). Compared to wound closure in normal skin, ischemic skin wounds exhibited delayed closure, and the length of delay correlated with the degree of surgically induced ischemia. TP508 significantly accelerated closure in both normal and ischemic skin, resulting in closure rates that were increased within the first 7 days of wounding by 30% in normal tissue and bipedicle flaps, 50% in cranially based flaps, and 225% in free grafts. Moreover, in both flap models, TP508 restored the rate of closure to a rate approximating the control rate observed in normal skin. Histological comparisons of wound tissue from normal skin and cranially based flaps showed that ischemia reduced early recruitment of inflammatory cells at day 1 but increased inflammatory cell numbers in wound beds at day 14. TP508 treatment of ischemic flap wounds significantly increased early inflammatory cell recruitment and restored the normal rapid resolution of the inflammatory phase. In addition, at day 7, TP508-treated wounds appeared to have an increased number of large functional blood vessels compared to saline controls. These studies support the potential efficacy of TP508 in treating ischemic wounds in humans.     

应用小阴唇扩张皮瓣的阴道形成术

目的　探索应用软组织扩张器扩张小阴唇组织 ,以小阴唇扩张皮瓣行阴道形成术的方法。方法　选择 3cm× 5cm、5 0ml肾形扩张器 ,置入小阴唇内外侧壁之间及阴唇间沟 ,扩张小阴唇 ,以获取足够面积的小阴唇组织。于尿道膀胱与直肠间造穴 ,翻转蒂在阴唇后联合处的小阴唇双叶皮瓣 ,以小阴唇皮瓣衬覆阴道腔壁 ,完成阴道形成术 ;术后夜间佩带模具 3～ 6个月。结果　本组5例经术后 6个月～ 2年随访 ,4例已结婚 ,性生活满意 ;外阴形态正常 ,再造阴道外口大于 2横指 ,深度≥ 8cm ,具有感觉和分泌功能 ,接近生理需要。结论　应用软组织扩张器扩张小阴唇形成阴道是诸多阴道形成术中较为理想的方法 ,其损伤小 ,并发症少 ,再造阴道接近解剖及生理状态。     

Bipedicle fasciocutaneous flaps for inframalleolar vascular graft coverage at the ankle/foot.

In 9 patients requiring inframalleolar bypass (11 extremities), intraoperative consult revealed exposed saphenous vein grafts at either the medial ankle or the dorsum of the foot in which primary wound closure resulted in the reduction or occlusion of blood flow. In these patients, longitudinally oriented bipedicle fasciocutaneous flaps were raised with widths of 3 to 4 cm and lengths ranging from 12 to 18 cm, with Doppler confirmation of discrete fascial perforators. Split-thickness skin grafts were placed in the wake of the flaps. Patient follow-up ranged from 2 to 78 months. All wounds healed, and 10 of 11 limbs were salvaged. Bipedicle flap coverage allows reconstruction of soft-tissue defects with the transposition of local tissues of similar qualities, avoiding the need for more complex distant tissue reconstruction. The inclusion of the deep fascia with the flap enhances its vascular perfusion, even in the ischemic lower extremity, with concurrent revascularization. The reliability of this type of flap is not dependent on traditional concepts of length-to-width ratios, but rather on standard principles of angiosome anatomy.     

应用胫后动脉穿支皮瓣修复足踝部复杂开放性骨折创面

目的：探讨胫后动脉穿支皮瓣在足踝部创面修复中的临床应用。方法应用胫后动脉穿支皮瓣逆行转移修复足踝部复杂开放性骨折创面6例。皮瓣切取面积：5.0 cm＆#215;6.0 cm～10.0 cm＆#215;15.0 cm。结果本组4例皮瓣全部成活,2例皮瓣边缘部分坏死,经换药及游离植皮后愈合。术后随访5～24个月,皮瓣外形满意,血供良好,无感染病例发生,足踝部骨折均骨性愈合,患肢均能负重行走。结论胫后动脉穿支皮瓣具有血供良好、操作简单、皮瓣供区破坏小等优点,适合修复足踝部皮肤软组织缺损。     

Reconstruction of ear helix: use of self-tubing pedicle flap

The tube pedicle flap is useful in reconstruction of an absent ear helix. However, immediate tubing of the flap may result in vascular compromise. By elevating a bipedicle flap in the postauricular region and shielding it with a silicone sheet, it is possible to allow the flap to assume a tubular shape while preventing adherence to the underlying suture line. Once mature, the flap maintains both a cylindrical shape and a sufficiently thin external diameter to provide adequate restoration of the ear helix.     

A silicone gel sheet dressing containing an antimicrobial agent for split thickness donor site wounds

Treatment of a split thickness donor site wound in 20 patients by means of a silicone gel sheet containing Ofloxacin, an antimicrobial agent, has been tested. For a comparison, each wound was divided into two parts, one for the silicone gel treatment and the other with a collagen sheet (10 cases) or an ointment-impregnated gauze (10 cases). Although Staphylococcus aureus was detected in three wounds treated with the collagen sheet, no wound treated with the silicone gel developed an infection even though the infected wound was adjacent. Results have shown that prompt epithelialisation occurred in the silicone gel-covered wounds, with little exudate and pain compared to wounds treated with either of the dressings. Although some wounds treated with the silicone gel tended to exhibit a slightly prolonged redness compared to wounds treated with an ointment-impregnated gauze, no subsequent cosmetic problem resulted.     

穿支皮瓣修复四肢创面临床应用56例

目的 探讨应用穿支皮瓣修复四肢创面的临床效果。方法 自2016年11月至2018年10月,采用股前外侧穿支皮瓣(ALTP)、腹壁下动脉穿支皮瓣(DIEP)、骨间后动脉穿支皮瓣(PIAP)、胸背动脉穿支皮瓣(TDAP)、腓肠内侧动脉穿支皮瓣(MSAP)、桡侧副动脉穿支皮瓣(RCAP)游离移植修复四肢创面56例,软组织缺损面积1.5 cm×1.5 cm~ 10.0 cm×24.0 cm,皮瓣切取面积2.0 cm×2.0 cm~ 11.0 cm×25.0 cm。供区均直接缝合关闭。术后观察皮瓣成活与创面愈合情况,定期随访皮瓣外观、质地、肢体功能恢复及皮瓣供区外形及功能。结果 1例DIEP移植术后第3天发生静脉危象,经手术探查重新吻合静脉后成活,皮瓣远端部分表皮坏死,经换药治疗后愈合;其余55例皮瓣均顺利成活,皮瓣受区与供区创口均一期愈合。术后6~ 18个月随访,皮瓣颜色正常,质地柔软,肢体功能恢复良好,皮瓣供区仅残留线形瘢痕,功能无影响。结论 穿支皮瓣修复四肢创面疗效可靠,可以推广应用。     

Wassergefiltertes Infrarot A (wIRA) hilft Wunden heilen

Water-filtered infrared-A (wIRA) is a special form of heat radiation with high tissue penetration and low thermal load to the skin surface which promotes the healing of acute and chronic wounds both by thermal and thermic as well as by non-thermal and non-thermic effects. Water-filtered infrared-A increases tissue temperature (+?2.7?°C at a tissue depth of 2 cm), tissue oxygen partial pressure (+?32?% at a tissue depth of 2 cm) and tissue perfusion. These three factors are decisive for a sufficient supply of tissue with energy and oxygen and consequently also for wound healing and infection defense. Water-filtered infrared-A promotes normal as well as disturbed wound healing by diminishing inflammation and exudation, by promotion of infection defense and regeneration, and by alleviation of pain. These effects have been proven in a total of seven prospective studies (of these six randomized controlled studies) with most of the effects having an evidence level of Ia or Ib. The additional cases of complicated courses of wound healing presented in this article illustrate the proven effects of wIRA. Not only in the 6 presented cases wIRA turned the complicated courses of wound healing for the better and facilitated the healing of the wounds after varying total times of irradiation (in the 6 cases 51–550 h) and after variable times of wound care and mostly after transplantation of split skin grafts. In complicated courses of wound healing wIRA does not replace consultation and, when indicated, treatment by an experienced plastic surgeon and by a surgeon specialized in septic surgery. With these limitations wIRA can be recommended as a valuable complement for the treatment of acute as well as of chronic wounds.     

依创面立体定形游离皮瓣的临床应用

目的：探讨应用游离皮瓣修复软组织缺损的方法及效果。方法：选择24例需要行游离皮瓣修复创面的患者,根据其软组织的不同缺损情况,取无菌棉布片制作与创面相同形状的模板,切下皮瓣后依据创面的形状及深度修剪掉皮瓣多余的脂肪组织,保留皮瓣的营养血管网,制备成立体的定形皮瓣填补创面缺损。皮瓣切取面积最小1．5cm×2．5cm,最大12cm×24cm,供区直接缝合或中厚皮片修复。结果：术后皮瓣全部成活,创面修复后表面平坦,术后随访13例,随访时间3-36个月,皮瓣颜色、质地和厚薄与受区相近,外形、功能恢复满意。皮瓣感觉恢复至S2-S4。结论：立体定形皮瓣兼顾了受区外形与功能的修复,是创面美容修复的理想方法。     

Energy metabolism of experimental wounds at various oxygen environments.

Energy metabolism of healing tissue was studied in experimental wounds of rats chronically breathing 11% O2, air or 55% O2. Increasing oxygen supply elevated both PO2 and PCO2 in the wound tissue. At the early phases of healing hypoxic wounds contained less DNA than normoxic or hyperoxic tissues. In hypoxia the accumulation of wound collagen was clearly retarded. Furthermore, tissue taken from wounds healing in hypoxic environments and tested ex vivo in air showed decreased capacity for glucose utilization, lactate production and oxygen consumption. Concentrations of AMP, ADP and ATP in repair tissue increased as healing progressed. The more oxygen available the higher the amounts of ADP and ATP. The AMP content was not affected by changes in local oxygen tension. These results support the earlier concept that the supply of oxygen in healing tissue may be rate-limitimg. Reduction of available oxygen either by systemic hypoxia or by increased diffusion distance impedes healing.     

感染缺损性创面岛状皮瓣修复的实验研究

目的：探讨皮瓣修复感染性创面机理，为临床提供实验依据。方法：实验选用兔侧胸岛状皮瓣转移修复皮肤、肌肉、骨骼缺损性创面。通过接种不同浓度绿脓杆菌混合液，观察修复后创面渗出液、皮瓣深浅层组织细菌数变化以及血流量改变，结合皮瓣成活、组织学检查等观察。结果：岛状皮瓣修复感染性创面在创面细菌数高于１０７个／ｍｌ时，皮瓣难以成活。结论：岛状皮瓣修复感染性创面与血供及白细胞吞噬功能存在密切关系，移植皮瓣修复感染创面是有一定限度的，且皮瓣深浅层抗菌力是不同的，以深筋膜层较强。     

Tissue salvage by mapping of skin surface transcutaneous oxygen tension index

Healing of both pathologic and surgical wounds is strongly dependent on adequate skin blood flow and oxygenation. The transcutaneous oxygen tension (PtcO2) index (regional PtcO2 index = RPI = limb PtcO2/chest PtcO2) and wound healing were assessed prospectively in 159 wounds in 113 high-risk patients referred for standard noninvasive tests. Patients were managed by referring practitioners on the basis of clinical assessment and standard tests. Treatment was divided into local procedures and amputations. Of 93 local procedures, 48 healed (RPI = 0.72 +/- 0.10 [mean +/- SD]) and 45 failed (RPI = 0.25 +/- 0.12). Of 66 amputations, 45 healed (RPI = 0.64 +/- 0.09) and 21 failed (RPI = 0.28 +/- 0.11). Well-oxygenated skin healed reliably regardless of the cause of the wound. Regional skin oxygenation studies aid rapid diagnosis of ischemia and allow maximal conservation of tissue in limb salvage situations.