Anterior Neck Resurfacing Using Multiple Free Flaps in Patients With Burn Sequelae of the Anterior Neck and Chest.

BACKGROUND: It has been established that patients with burn sequelae of the anterior neck and chest have a significant degree of flap descent and deficit in neck extension when resurfaced with a single free flap. A protocol was developed to avoid flap descent in these patients by resurfacing the neck with multiple free flaps. The purpose of this article is to present our protocol for treatment and long-term results of this technique. METHODS: Twenty-five 25 patients with burn sequelae of the anterior neck and anterior thorax were retrospectively identified. Ten patients were treated with a single free flap (group 1), and 15 patients were treated with multiple free flaps (group 2). Patients were followed up for an average of 7 years after their definitive reconstructive procedure at which time measurements including flap descent from sternal notch, deficit of neck extension, and subjective reports of discomfort were obtained. RESULTS: Patients in group 1 demonstrated 8 cm (interquartile range [IQR], 1.75 cm) of flap descent, whereas patients in group 2 demonstrated 0.5 cm (IQR, 0 cm) of flap descent. Patients in group 1 demonstrated 12.5 degrees (IQR, 10 degrees) of deficit in neck extension, whereas patients in group 2 demonstrated 0 degrees (IQR, 0 degrees) of deficit in neck extension. Analysis demonstrated significantly greater descent and deficit in neck extension in group 1 compared with group 2. CONCLUSIONS: Patients with burn sequelae of the neck and anterior chest experience less flap descent and deficits in neck extension when resurfaced with multiple free flaps.

The Deltopectoral/Internal Mammary Artery Perforator Flap Revisited: Design Variations Based on Cadaveric and Clinical Investigation.

ABSTRACT: Current understanding of the vascular anatomy of the anterior chest wall suggests that perfusion of the deltopectoral flap may be compromised when crossing the midline at the anterior thoracic wall. The traditional deltopectoral flap is designed longitudinally over the ipsilateral side to avoid the risk of distal flap necrosis. The purpose of this article is to present our experience and results with 26 deltopectoral flaps that were designed and raised with the perforating vessels on the ipsilateral side with the majority of the flap crossing the midline extending to the contralateral side. This anatomic variation in flap design indicates that the sternal midline is not a barrier and that the internal mammary perforator flap may be raised on different longitudinal axes.

Anterior Neck Resurfacing Using a Single Free Flap: Comparison of Flap Descent in Patients With Burn Sequelae of the Neck/Chest and Patients With Burn Sequelae of Only the Neck.

BACKGROUND: Burn sequelae involving the anterior neck and thorax produce a difficult challenge for reconstruction because contracture of anterior thoracic burns in addition to functional movement of the chest wall can result in downward displacement of the neck unit. The purpose of this study was to understand the influence of burn sequelae of the anterior thorax on anterior neck flap descent, function, and aesthetics. METHODS: Ten patients with burn sequelae of only the anterior neck (group 1) and 10 additional patients with burn sequelae of the anterior neck and thorax (group 2) were retrospectively identified. All 20 patients were treated with scar release and a single extended circumflex scapular free flap for neck resurfacing. Patients were followed for an average of 10 years, at which time flap descent from the sternal notch, deficit of neck extension, and subjective reports of discomfort were measured. RESULTS: Patients in group 1 experienced a median flap descent of 0 [interquartile range (IQR), 1.62 cm] and a median deficit of 0° (IQR, 5°) during neck extension. Patients in group 2 experienced a median flap descent of 8 cm (IQR, 1.75 cm) and a median deficit of 12.5° (IQR, 10°) during neck extension. Retrospective analysis of the 10 patients with burn sequelae of the anterior neck and thorax (group 2) demonstrated a significantly greater degree of flap descent and deficit of neck extension compared with the 10 patients with burn sequelae of only the anterior neck (group 1). Patients in group 1 also subjectively reported less discomfort at follow-up compared with patients in group 2. CONCLUSIONS: We conclude that patients with burn sequelae involving the anterior neck and thorax have a significantly greater degree of flap descent and neck extension compared with patients with burn sequelae involving only the anterior neck. Flaps of a larger surface area or use of multiple flaps for neck resurfacing may be considered to avoid significant flap descent associated with burn sequelae involving both the anterior neck and thorax.

Initial Clinical Experience with Dual-Agent Relaxation Contrast for Isolated Lymphatic Channel Mapping.

Purpose To evaluate the clinical performance of dual-agent relaxation contrast (DARC) magnetic resonance (MR) lymphangiography compared with that of conventional MR lymphangiography in the creation of isolated lymphatic maps in patients with secondary lymphedema. Materials and Methods This retrospective study was approved by the institutional review board. The diagnostic quality of 42 DARC MR lymphangiographic studies was compared with that of 42 conventional MR lymphangiographic studies. Two independent readers rated venous contamination as absent, mild, or moderate to severe. Interreader agreement on venous contamination grades was assessed by using the linearly weighted Cohen κ statistic. The Mann-Whitney U test was used to compare the distribution of grades at each station between conventional MR lymphangiography and DARC MR lymphangiography for each reader separately. Results DARC MR lymphangiography had significantly less venous contamination than did conventional MR lymphangiography (P < .001). The two radiologists rated venous contamination as moderate to severe in 64% (27 of 42) and 69% (29 of 42) of distal limbs, 23% (10 of 42) of midlimbs, and 2% (one of 42) and 9% (four of 42) of proximal limbs at conventional MR lymphangiography compared with 0% (0 of 42) of distal limbs, 2% (one of 42) of midlimbs, and 0% (0 of 42) of proximal limbs at DARC MR lymphangiography. Lymphatic signal was partially attenuated (median 45% decrease) when longer echo times were used for venous suppression, but it did not subjectively degrade diagnostic quality. Conclusion DARC MR lymphangiography yields isolated lymphatic maps through nulling of venous contamination, thereby simplifying diagnostic interpretation and communication with surgical colleagues. © RSNA, 2017.

Lymph node transplantation for the treatment of lymphedema.

Lymphedema is a complex disease process with deranged lymphatic transport, fluid accumulation and secondary lipedema and fibrosis. This is a challenging disease to treat with a surgical focus on debulking and physiologic strategies. One strategy is the use of vascularized lymph node transplant (VLNT) to improve physiologic lymph clearance. In this article, VLNT is discussed in detail, including mechanisms, combined strategies, and outcomes.

MR lymphangiography in the treatment of lymphedema.

Lymphedema is a common condition frequently seen in cancer patients who have had lymph node dissection +/- radiation treatment. Traditional management is mainly non-surgical and unsatisfactory. Surgical treatment has relied on excisional techniques in the past. Physiologic operations have more recently been devised to help improve this condition. Assessing patients and deciding which of the available operations to offer them can be challenging. MRI is an extremely useful tool in patient assessment and treatment planning. J. Surg. Oncol. 2017;115:18-22. © 2016 Wiley Periodicals, Inc.

Comparison of Synthetic and Biologic Mesh in Ventral Hernia Repair Using Components Separation Technique.

Ventral hernia repair (VHR) for large abdominal wall defects is challenging. Prior research established that the use of mesh is superior to suture closure alone and that component separation is an effective technique to combat loss of abdominal domain. Studies comparing component separation technique (CST) outcomes utilizing synthetic versus biologic mesh are limited. A retrospective review was conducted of 72 consecutive patients who underwent VHR with CST between 2006 and 2010 at our institution. Surgeon preference and the presence of contamination guided whether synthetic mesh (27 patients) or biologic mesh (45 patients) was used. Mean follow-up interval for all comers was 13.9 months and similar in both groups (P > 0.05). Degree of contamination and severity of premorbid medical conditions were significantly higher in the biologic mesh group, as reflected in the higher Ventral Hernia Working Group (VHWG) score (2.04 versus 2.86). Clinical outcomes, as measured by both minor and major complication rates and recurrence rates, were not significantly different. Minor complication rates were 26% in the synthetic group and 37% in the biologic group and major complication rates 15% in the synthetic group and 22% in the biologic group. There was 1 recurrence (4%) in the synthetic mesh group versus 5 (11%) in the biologic mesh group. Multivariable analysis for major complications revealed no significant difference for either synthetic or biologic mesh while controlling for other variables. Subset analysis of uncontaminated cases revealed recurrence rates of 4% in the synthetic mesh group and 6% in the biologic mesh group. VHR using CST and either synthetic mesh or biologic mesh resulted in low recurrence rates with similar overall complication profiles, despite the higher average VHWG grading score in the biologic mesh group. Our results support the VHWG recommendation for biologic mesh utilization in higher VHWG grade patients. In VHWG grade 2 patients, our clinical outcomes were similar, supporting the use of either type of mesh.

MR lymphangiography: How i do it.

Lymphedema is a chronic progressive edematous disease that in the United States is most commonly related to malignancy and its treatment. Lymphaticovenular anastomosis is a recently introduced microsurgical treatment option for lymphedema that requires the identification and mapping of individual lymphatic channels. While nuclear medicine lymphoscintigraphy has been the primary imaging modality performed to evaluate suspected lymphedema, lymphoscintigraphy does not provide the spatial information necessary for presurgical planning. High-resolution dynamic 3D magnetic resonance imaging (MRI) can noninvasively image abnormal lymphatic channels to both diagnose lymphedema and depict the location and number of individual lymphatic channels for surgical planning. MR lymphangiography can be performed at 1.5T or 3.0T using multichannel phased array surface coils. The main components of the exam are a heavily T2 -weighted 3D sequence to define the severity and extent of edema, a high-resolution dynamic 3D gradient echo imaging after intracutaneous contrast injection to visualize lymphatic channels, and a delayed 3D gradient echo sequence after intravenous contrast to define veins. This article reviews the pathophysiology and microsurgical treatment of lymphedema, presents the imaging protocol used at our institution, and describes exam interpretation and the image postprocessing performed for surgical planning.

Comparison of outcomes using AlloDerm versus FlexHD for implant-based breast reconstruction.

BACKGROUND: Prosthetic reconstruction using human acellular dermis (ADM) is a common practice in breast reconstruction. AlloDerm and FlexHD are two different forms of ADM, each with unique characteristics. No studies have directly compared the postoperative complications of these 2 products. METHODS: The outcomes of 547 consecutive implant-based breast reconstructions were reviewed. RESULTS: Reconstruction was performed in 382 consecutive women (547 total breasts), employing mostly immediate reconstruction (81%). Mean follow-up was 6.4 months. Among immediate reconstructions, 165 used AlloDerm and 97 used FlexHD. Complications were similar by univariate analysis. In multivariate analysis, smoking and higher initial implant fill were risk factors for delayed healing. The use of FlexHD, single-stage reconstruction, and smoking were independent risk factors for implant loss. CONCLUSIONS: There is no significant difference in the complication rates between AlloDerm and FlexHD in immediate breast reconstruction. Multivariate analysis suggests that FlexHD may be a risk factor for implant loss.

Useful Flaps for Plastic Surgeons to Know.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe different useful flaps. 2. Identify pitfalls of specific flaps. 3. Incorporate tips that facilitate flap use. SUMMARY: We have a wide selection of flaps to choose from for any given reconstruction. This article describes the use of different flaps that the author has found useful in his practice. Some of these flaps are mainstream, whereas others are not. The article does not suggest that these are the only flaps that one should use, nor does it go into great detail on the dissection of each flap except where the author has identified pitfalls or where he can offer tips and tricks that facilitate use of these flaps. Flaps are described from head to toe.

Decompression of Axillary vein - An essential adjunct for advanced lymphedema.

INTRODUCTION: In advanced lymphedema, lymphovenous anastomosis (LVA) can be a solution based on utilizing the pressure gradient between the high pressure lymphatics and low pressure veins. If the vein pressure in high, the effect affect surgery will be less optimal. This study evaluated the effect of axillary vein perivascular scar release on LVA. MATERIALS AND METHODS: This is a retrospective study of 40 upper limb stage 2 and 3 lymphedema patients divided into 2 groups with an average follow-up of 33 months (minimal of at least 12 months); scar-released group (n=25) and control group (n=15). All patients underwent LVA with or without lymph node transfer. Demographic data, outcome (volumetric change and bioimpedence analysis (BIA)), and major veins (axillary, basilic and cephalic) diameter changes were evaluated. RESULTS: Both groups showed significant reduction in volume and BIA parameters after LVA. The scar-released groups (24/25 with lymph node transfer and 1 without) showed statistically higher reduction of BIA analysis compared to the control group at 1, 6 and 12 months after LVA. The changes in the major veins after axilla scar release showed significant changes in all 3 veins. There was a significant correlation between cephailic vein dimeter reduction and BIA measurement. CONCLUSION: The release of perivascular scar in the axially vein may result in better outcome after LVA. This is based on the finding that scar release shows correlation between cephailic vein dimeter reduction and BIA measurement suggesting reduction of venous pressure in the peripheral vein increasing the pressure gradient between the lymphatic and venous system allowing better outflow after LVA.

Vasorelaxation effect and mechanism of action of vascular endothelial growth factor-165 in isolated perfused human skin flaps.

BACKGROUND: Experimental evidence is accumulating to indicate that local acute vascular endothelial growth factor-165 (VEGF(165)) therapy is effective in attenuation of skin ischemia and increase in skin viability in rat skin flap surgery and the mechanism involves vasodilation induced by VEGF(165). So far, the vasodilator effect and mechanism of action of VEGF(165) have not been studied in human skin. The objective of this project is to test the hypothesis that VEGF(165) is also a potent vasodilator in human skin vasculature. MATERIALS AND METHODS: We used an established isolated perfused human skin flap model and pharmacologic probes to demonstrate that VEGF(165) is a potent vasodilator in human skin vasculature and the mechanism involves activation of receptors and postreceptor signaling pathway, which in turn stimulates local synthesis/release of endothelial vasodilators. RESULTS: We observed that VEGF(165) induced a concentration-dependent vasorelaxation in human skin flaps preconstricted with norephinephrine (8 × 10(-7)M; n = 7) or endothelin-1 (3 × 10(-9)M; n = 6). The vasorelaxation potency of VEGF(165) (pD(2) = 12.02 ± 0.25; n = 7) was higher (P < 0.05) than that of acetylcholine (pD(2) = 6.76 ± 0.06; n = 5) in human skin flaps preconstricted with 8 x 10(-7)M of norepinephrine. Using pharmacologic probes, we also detected that the vasorelaxation effect of VEGF(165) in the isolated perfused human skin flaps (n = 4) was triggered by activation of VEGF receptor-2. Furthermore, the postreceptor signaling pathway involved activation of Src family tyrosine kinase, phospholipase C, protein kinase C, an increase in inositol 1,4,5-triphosphate activity, a release of the intracellular Ca(2+) store, and finally synthesis/release of the endothelial nitric oxide (eNO) and prostacyclin and eNO predominantly mediated the vasodilator effect of VEGF(165) in the effector mechanism. CONCLUSION: These findings support our hypothesis that VEGF(165) is a potent vasodilator in human skin vasculature and also provide important insights into the clinical study of local acute VEGF(165) therapy for prevention/treatment of skin ischemia in skin flap surgery.

Updates on Excisional Procedures for Lymphedema.

Significance: Excisional procedures for lymphedema have been used for over a century, and many surgeons have abandoned the old techniques as improvements in nonsurgical management and microsurgery have limited their clinical utility. Nonetheless, excisional procedures remain relevant as an important tool in the comprehensive surgical management of lymphedema. Recent Advances: Modifications to the Charles procedure and other direct excisional procedures have improved the complication profile and patient outcomes. Moreover, the use of liposuction techniques for minimally invasive tissue excision has expanded the scope of excisional surgery to benefit patients with less severe lymphedema. Recent operations combining excisional and physiologic procedures may prove to have superior results to stand-alone procedures. Critical Issues: No standard protocol exists for the comprehensive surgical management of lymphedema. Proper patient selection for any procedure requires robust outpatient assessment, cooperation with physiotherapy treatment teams, careful patient stratification, and a clear understanding of the procedure's goal. Future Directions: Larger, prospective trials will be needed to elucidate the ideal timing and combinations of techniques to optimize outcomes for patients with late-stage lymphedema.

Use of fluorescence imaging during lymphatic surgery: A Delphi survey of experts worldwide.

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly used during lymphedema patient management. However, to date, no guidelines exist on when it should and should not be used or how it should be performed. Our objective was to have an international panel of experts identify areas of consensus and nonconsensus in current attitudes and practices in fluorescence imaging with indocyanine green use during lymphedema surgery patient management. METHODS: A 2-round Delphi study was conducted involving 18 experts in the use of fluorescence imaging during lymphatic surgery, all asked to vote on 49 statements on patient preparation and contraindications (n = 7 statements), indocyanine green dosing and administration (n = 10), fluorescence imaging uses and potential advantages (n = 16), and potential disadvantages and training needs (n = 16). RESULTS: Consensus ultimately was reached on 40/49 statements, including consistent consensus regarding the value of fluorescence imaging with indocyanine green in almost all facets of lymphedema patient management, including early detection, assessing disease extent, preoperative work-up, surgical planning, intraoperative guidance, monitoring short- and longer-term outcomes, quality control, and resident training. All experts felt it was very safe, while 94% felt it should be part of routine care and that indocyanine green was superior to colored dyes and ultrasound. Nonetheless, there also was consensus that limited high-quality evidence remains a barrier to its widespread use and that patients should still be provided with specific information and asked to sign specific consent for both fluorescence imaging and indocyanine green. CONCLUSION: Fluorescence imaging with or without indocyanine green appears to have several roles in lymphedema prevention, diagnosis, assessment, and treatment.

Delphi survey of intercontinental experts to identify areas of consensus on the use of indocyanine green angiography for tissue perfusion assessment during plastic and reconstructive surgery.

BACKGROUND: In recent years, indocyanine green angiography (ICG-A) has been used increasingly to assist tissue perfusion assessments during plastic and reconstructive surgery procedures, but no guidelines exist regarding its use. We sought to identify areas of consensus and non-consensus among international experts on the use of ICG-A for tissue-perfusion assessments during plastic and reconstructive surgery. METHODS: A two-round, online Delphi survey was conducted of 22 international experts from four continents asking them to vote on 79 statements divided into five modules: module 1 = patient preparation and contraindications (n = 11 statements); module 2 = ICG administration and camera settings (n = 17); module 3 = other factors impacting perfusion assessments (n = 10); module 4 = specific indications, including trauma debridement (n = 9), mastectomy skin flaps (n = 6), and free flap reconstruction (n = 8); and module 5 = general advantages and disadvantages, training, insurance coverage issues, and future directions (n = 18). Consensus was defined as ≥70% inter-voter agreement. RESULTS: Consensus was reached on 73/79 statements, including the overall value, advantages, and limitations of ICG-A in numerous surgical settings; also, on the dose (0.05 mg/kg) and timing of ICG administration (∼20-60 seconds preassessment) and best camera angle (61-90o) and target-to-tissue distance (20-30 cm). However, consensus also was reached that camera angle and distance can vary, depending on the make of camera, and that further research is necessary to technically optimize this imaging tool. The experts also agreed that ambient light, patient body temperature, and vasopressor use impact perfusion assessments. CONCLUSION: ICG-A aids perfusion assessments during plastic and reconstructive surgery and should no longer be considered experimental. It has become an important surgical tool.

The application of indocyanine green fluorescence angiography in plastic surgery.

In flap reconstruction of complex defects the perfusion of the reconstructive flap is critical to the ultimate success of the reconstruction. This is especially true in perforator-based flaps where it can be difficult to assess the adequacy of perfusion in the operating room. However, the ability to definitively determine the degree of flap perfusion is imperative to clinical decision-making. An emerging technology using near-infrared angiography with indocyanine green (ICG) dye may significantly improve the immediacy and accuracy of the assessment of flap perfusion. This article reviews the current state of ICG angiography and its use in clinical practice in plastic surgery. There are 17 case series, including a total of 386 patients, published in the literature using ICG angiography in various plastic surgical procedures. ICG angiography may aid flap design and assessment in the intraoperative/postoperative settings, reduce complications, and ultimately improve outcomes.

Surgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference.

BACKGROUND: The goal of this consensus conference, sponsored by the American Association of Plastic Surgeons, was to perform a systematic review and meta-analysis of controlled trials to examine both the benefits and risks of surgical treatment and surgical prevention of upper and lower extremity lymphedema. METHODS: The panel met in Boston for a 3-day, face-to-face meeting in July of 2017. After an exhaustive review of the existing literature, the authors created consensus recommendations using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Important directions for future research were also identified. RESULTS: There is evidence to support that lymphovenous anastomosis can be effective in reducing severity of lymphedema (grade 1C). There is evidence to support that vascular lymph node transplantation can be effective in reducing severity of lymphedema (grade 1B). Currently, there is no consensus on which procedure (lymphovenous bypass versus vascular lymph node transplantation) is more effective (grade 2C). A few studies show that prophylactic lymphovenous bypass in patients undergoing extremity lymphadenectomy may reduce the incidence of lymphedema (grade 1B). More studies with longer follow-up are required to confirm this benefit. Debulking procedures such as liposuction are effective in addressing a nonfluid component such as fat involving lymphedema (grade 1C). There is a role for liposuction combined with physiologic procedures although the timing of each procedure is currently unresolved (grade 1C). CONCLUSIONS: Many studies seem to support some efficacy of lymphovenous bypass and vascular lymph node transplantation. Many studies show the important role of lymphedema therapy and other procedures such as liposuction and debulking. The management of lymphedema is a challenging field with many promising advances. However, many questions remain unanswered.

Current techniques in preoperative imaging for abdomen-based perforator flap microsurgical breast reconstruction.

Perforator-based microsurgical reconstruction of the breast has steadily increased since the introduction of the technique in the 1990s. The procedure appears to offer less postoperative pain, lower abdominal morbidity, and better preservation of the rectus muscles than the more conventional flaps. However, the major disadvantage of these flaps that they can be difficult to harvest, resulting in a longer operative times. The challenges in flap dissection are a result of the variability in the vascular anatomy of the deep inferior epigastric artery (DIEA) and its perforating branches through the rectus muscle. The location, number, and caliber of the perforators and the intramuscular trajectory of the DIEA branches vary greatly not only from individual to individual, but from one hemiabdomen to the other. The establishment of a presurgical map of the vessels on the abdomen facilitates surgical planning and may decrease operating room time, reduce intraoperative complications, and possibly improve outcomes. This article reviews the available techniques for preoperative planning with the currently available imaging modalities of handheld Doppler, color Doppler (duplex) ultrasound, computed tomography angiography, and magnetic resonance angiography.

The New 2019 Institutional Review Board Common Rule Update: Implications for Plastic Surgery Research.

Clinical research remains at the forefront of academic practice and evidence-based medicine. Unfortunately, history has shown that human subjects are vulnerable to experimentation without regard for their own dignity and informed decision-making. Subsequently, it is vital for research institutes to uphold safeguards and ethical conscientiousness toward human subjects. The establishment of federal regulations and the development of institutional review boards have set guidance on these processes. On January 21, 2019, final revisions to the Federal Policy for the Protection of Human Subjects (the "Common Rule") went into effect. The purpose of this article is to review changes to the Common Rule and discuss their impact on plastic surgery research.

Na+/H+ exchange inhibitor cariporide attenuates skeletal muscle infarction when administered before ischemia or reperfusion.

Administration of Na(+)/H(+) exchange isoform-1 (NHE-1) inhibitors before ischemia has been shown to attenuate myocardial infarction in several animal models of ischemia-reperfusion injury. However, controversy still exists as to the efficacy of NHE-1 inhibitors in protection of myocardial infarction when administered at the onset of reperfusion. Furthermore, the efficacy of NHE-1 inhibition in protection of skeletal muscle from infarction (necrosis) has not been studied. This information has potential clinical applications in prevention or salvage of skeletal muscle from ischemia-reperfusion injury in elective and trauma reconstructive surgery. The objective of this research project is to test our hypothesis that the NHE-1 inhibitor cariporide is effective in protection of skeletal muscle from infarction when administered at the onset of sustained ischemia or reperfusion and to study the mechanism of action of cariporide. In our studies, we observed that intravenous administration of cariporide 10 min before ischemia (1 or 3 mg/kg) or reperfusion (3 mg/kg) significantly reduced infarction in pig latissimus dorsi muscle flaps compared with the control, when these muscle flaps were subjected to 4 h of ischemia and 48 h of reperfusion (P < 0.05; n = 5 pigs/group). Both preischemic and postischemic cariporide treatment (3 mg/kg) induced a significant decrease in muscle myeloperoxidase activity and mitochondrial-free Ca(2+) content and a significant increase in muscle ATP content within 2 h of reperfusion (P < 0.05; n = 4 pigs/group). Preischemic and postischemic cariporide treatment (3 mg/kg) also significantly inhibited muscle NHE-1 protein expression within 2 h of reperfusion after 4 h of ischemia, compared with the control (P < 0.05; n = 3 pigs/group). These observations support our hypothesis that cariporide attenuates skeletal muscle infarction when administered at the onset of ischemia or reperfusion, and the mechanism involves attenuation of neutrophil accumulation and mitochondrial-free Ca(2+) overload and preservation of ATP synthesis in the early stage of reperfusion.