Anterolateral Ligament Reconstruction and Modified Lemaire Lateral Extra-Articular Tenodesis Similarly Improve Knee Stability After Anterior Cruciate Ligament Reconstruction: A Biomechanical Study.

PURPOSE: To determine the stabilizing role of anterolateral ligament reconstruction (ALLR) and modified Lemaire lateral extra-articular tenodesis (LET) performed in combination with anterior cruciate ligament reconstruction (ACLR) and to determine whether either procedure was superior to the other. METHODS: Six nonpaired, human, fresh-frozen cadaveric knees were tested with a 6-df robotic system. Internal rotation and anterior translation of the knee were recorded from 0° to 90° of flexion after application of a 5-Nm internal rotation torque and a 134-N anterior load, respectively. A full kinematic assessment was performed in each of the following conditions: (1) intact knee, (2) after sectioning of the anterior cruciate ligament (ACL), (3) after sectioning of the ACL and anterolateral ligament, (4) after isolated ACLR, and (5) after combined ACLR and Lemaire LET and combined ACLR and ALLR. ALLR was performed using the gracilis tendon, whereas the modified Lemaire procedure was performed using the central strip of the iliotibial band. The different states were compared using a Tukey paired comparison test. RESULTS: In knees with combined deficiency of the ACL and anterolateral structures, anterior translation and internal rotation remained significantly increased after isolated ACLR compared with the intact knee (+2.33 ± 1.44 mm and +1.98° ± 1.06°, respectively; P < .01). On the other hand, the addition of ALLR or modified Lemaire LET to ACLR restored anterior translation and internal rotation to values similar to those in the intact knee. The 2 anterolateral procedures did not show statistically significantly different values for both tests. This difference was 0.67 ± 1.46 mm for anterior translation (P = .79) and 0.11° ± 1.11° for internal rotation (P = .99). CONCLUSIONS: In knees with ACL and anterolateral deficiency, combined ACLR and anterolateral reconstruction restored the native knee stability in anterior translation and internal rotation contrary to isolated ACLR. In addition, both types of extra-articular reconstruction-ALLR and modified Lemaire LET-were similar in terms of restoring knee kinematics, and neither overconstrained the knee. CLINICAL RELEVANCE: In knees with deficiency of the ACL and anterolateral structures, combined ACLR and anterolateral reconstruction increased knee stability at time zero after surgery. This biomechanical improvement could be responsible for the protective effect on ACL graft and meniscal repair reported in the literature after the combined procedure.

Clinical Outcomes After Combined Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction.

BACKGROUND: Graft rupture rate, return to sport and persistent rotational instability remain a concern postoperatively following anterior cruciate ligament (ACL) reconstruction. The anterolateral ligament (ALL) has recently been shown to act as a lateral knee stabilizer that helps improve rotational stability. To improve functional and clinical outcomes, a combined ACL reconstruction with an associated ALL reconstruction has been proposed. PURPOSE: The main purpose of this study was to evaluate the clinical outcomes of the combined ACL and ALL reconstruction. METHODS: A literature search in PubMed was performed and papers reporting on clinical outcomes after combined ACL and ALL reconstruction were identified. The inclusion criteria was a minimum 2-year follow-up. RESULTS: Five studies were included in the review. The overall graft failure rate in patients with ACL and ALL reconstruction was <3% at 2 years minimum after surgery. Comparison analysis in a high-risk population demonstrated that the graft failure rate in combined ACL and ALL reconstruction was 2.5 times lower than with isolated bone-patella tendon-bone graft and 3.1 times lower than with isolated hamstring graft. The medial meniscal repair failure rate was also 2 times lower in the combined ACL and ALL reconstruction group compared with isolated ACL reconstruction. Return to sport and functional outcomes did not show any significant difference between the groups. The rate of reoperations was not increased in patients with combined ACL and ALL reconstruction. CONCLUSIONS: Overall, combined ACL and ALL reconstruction provides promising results that may improve graft rupture rates and meniscal repair failure rates, while maintaining excellent functional outcomes.

Biomechanical Comparison of Anterior Cruciate Ligament Reconstruction Using a Single-Bundle Round or Ribbon-like Hamstring Tendon Graft.

BACKGROUND: Persistent instability of the knee is reported in up to 30% of patients after anterior cruciate ligament (ACL) reconstruction. Based on anatomic findings showing that ACL is a flat ribbon-like structure that twists during knee flexion, a new surgical ACL reconstruction technique using a ribbon-like graft has been developed. However the effect of this surgical technique on knee kinematics has not yet been evaluated. PURPOSE: To compare the anteroposterior and rotational stability of the knee after ACL reconstruction using single-bundle (SB) round and ribbon-like grafts in anterolateral-intact/deficient knees. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve human fresh-frozen cadaveric knees were tested with a 6 degrees of freedom robotic system. Internal rotation and anterior translation of the knee were recorded from 0° to 90° of flexion. A full kinematic assessment was performed in each of the following conditions: (1) intact knee, (2) after sectioning of the ACL, (3) after ACL reconstruction using a SB hamstring tendon graft in a round configuration and a ribbon-like configuration, and (4) after sectioning of the anterolateral structures. One-way analysis of variance and post hoc Tukey tests were used for statistical analyses. RESULTS: When compared with the intact knee, the ACL-deficient knee demonstrated a mean ± SD increase in anterior translation and internal rotation of 6.3 ± 2.5 mm (P < .01) and 5.8°± 2.3° (P < .01), respectively. After ACL reconstruction using a SB ribbon-like graft, the mean difference in anterior translation and internal rotation as compared with the intact knee was -0.1 ± 1.5 mm (P = .842) and 0.0°± 1.1° (P = .999). These differences from the intact knee were also not significant after ACL reconstruction using a round graft (-0.1 ± 1.3 mm, P = .999; -0.5°± 1.5°, P = .401). In the ACL-reconstructed knee using either a ribbon-like or round graft, sectioning of the anterolateral structures did not induce a significant increase of anterior translation and internal rotation of the knee. CONCLUSION: ACL reconstruction using a SB ribbon-like or round graft restored the kinematics of the intact knee at time zero. Secondary sectioning of the anterolateral structures in the ACL-reconstructed knee using both types of graft did not significantly affect the anterior translation and internal rotation of the knee. CLINICAL RELEVANCE: This is the first biomechanical study on the new ACL reconstruction technique using a ribbon-like graft.

Isopropylamine NONOate (IPA/NO) moderates neointimal hyperplasia following vascular injury.

OBJECTIVE: Isopropylamine NONOate (IPA/NO) is a nitroxyl (HNO) donor at physiologic pH. HNO is a positive inotrope and vasodilator, but little is known about its effect on neointimal hyperplasia. The aims of this study are to determine the effect of IPA/NO on endothelial and vascular smooth muscle cells (VSMC) in vitro and to determine if IPA/NO inhibits neointimal hyperplasia in vivo. METHODS: VSMC were harvested from the abdominal aortas of male Sprague Dawley rats, and human umbilical vein endothelial cells were purchased from ATCC. In vitro, cellular proliferation was assessed by (3)H-thymidine incorporation, cell migration was assessed using the scrape assay, and cell death was assessed using Guava personal cell analysis (PCA). Cell cycle analysis was performed using propidium iodide staining and flow cytometry analysis. Protein expression was assessed using Western blot analysis. Phosphorylated proteins were assessed using immunoprecipitation and Western blot analysis. In vivo, the carotid artery injury model was performed on male Sprague Dawley rats treated with (n = 12) or without (n = 6) periadventitial IPA/NO (10 mg). Arteries harvested at 2 weeks were assessed for morphometrics using ImageJ. Inflammation was assessed using immunohistochemistry. Endothelialization was assessed by Evans blue staining of carotid arteries harvested 7 days after balloon injury from rats treated with (n = 6) or without (n = 3) periadventitial IPA/NO (10 mg). RESULTS: In vitro, 1000 micromol/L IPA/NO inhibited both VSMC (38.7 +/- 4.5% inhibition vs control, P = .003) and endothelial cell proliferation (54.0 +/- 2.9% inhibition vs control, P < or = 0.001) without inducing cell death or inhibiting migration. In VSMC, this inhibition was associated with an S-phase cell cycle arrest and increased expression of cyclin A, cyclin D1, and the cyclin-dependent kinase inhibitor p21. No change was noted in the phosphorylation status of cdk2, cdk4, or cdk6 by IPA/NO. In rodents subjected to the carotid artery balloon injury model, IPA/NO caused significant reductions in neointimal area (298 +/- 20 vs 422 +/- 30, P < or = .001) and medial area (311 +/- 14 vs 449 +/- 16, P < or = .001) compared with injury alone, and reduced macrophage infiltration to 1.7 +/- 0.8 from 16.1 +/- 3.5 cells per high power field (P < or = .001). IPA/NO also prevented re-endothelialization compared with injury alone (55.9 +/- 0.5% nonendothelialized vs 21 +/- 4.4%, respectively, P = .001). Lastly, a 50% mortality rate was observed in the IPA/NO-treated groups. CONCLUSIONS: In summary, while IPA/NO modestly inhibited neointimal hyperplasia by inhibiting VSMC proliferation and macrophage infiltration, it also inhibited endothelial cell proliferation and induced significant mortality in our animal model. Since HNO is being investigated as a treatment for congestive heart failure, our results raise some concerns about the use of IPA/NO in the vasculature and suggest that further studies be conducted on the safety of HNO donors in the cardiovascular system.

Knee Extension Deficit in the Early Postoperative Period Predisposes to Cyclops Syndrome After Anterior Cruciate Ligament Reconstruction: A Risk Factor Analysis in 3633 Patients From the SANTI Study Group Database.

BACKGROUND: Cyclops syndrome is characterized by a symptomatic extension deficit attributed to impingement of a cyclops lesion within the intercondylar notch. The syndrome is an important cause of reoperation after anterior cruciate ligament reconstruction (ACLR). It has been suggested that remnant-preserving ACLR techniques may predispose to cyclops syndrome, but there is very limited evidence to support this. In general terms, risk factors for cyclops syndrome are not well-understood. PURPOSE: To determine the frequency of and risk factors for reoperation for cyclops syndrome in a large series of patients after ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A retrospective analysis of prospectively collected data was performed, including all patients who underwent primary ACLR between January 2011 to December 2017. Patients undergoing major concomitant procedures were excluded. Demographic data, intraoperative findings (including the size of preserved remnants), and postoperative outcomes were recorded. Those patients who underwent reoperation for cyclops syndrome were identified, and potential risk factors were evaluated in multivariate analysis. RESULTS: A total of 3633 patients were included in the study, among whom 65 (1.8%) underwent reoperation for cyclops syndrome. Multivariate analysis demonstrated that preservation of large remnants did not predispose to cyclops lesions (odds ratio [OR], 1.11; 95% CI, 0.63-1.93). The most important risk factor was extension deficit in the early postoperative period. If present at 3 weeks postoperatively, it was associated with a >2-fold increased risk of cyclops syndrome (OR, 2.302; 95% CI, 1.268-4.239; P < .01), which was increased to 8-fold if present 6 weeks after ACLR (OR, 7.959; 95% CI, 4.442-14.405; P < .0001). None of the other potential risk factors evaluated were found to be significantly associated with an increased frequency of cyclops syndrome. CONCLUSION: Failure to regain full extension in the early postoperative period was the only significant risk factor for cyclops syndrome after ACLR in a large cohort of patients. Other previously hypothesized risk factors, such as preservation of a large anterior cruciate ligament remnant, did not predispose to the development of this debilitating postoperative complication.

Combined Anterior Cruciate Ligament Repair and Anterolateral Ligament Reconstruction.

There has been a renewed interest in anterior cruciate ligament (ACL) repairs over the last decade with some early promising results in the right patient population. Additionally, the anterolateral ligament has been extensively studied and has recently been shown to have a protective effect on standard ACL reconstructions in a clinical trial. Given its protective effect on ACL reconstructions, we believe this phenomenon is also relevant to ACL repairs and can decrease rerupture rates. In this publication, we demonstrate a surgical technique for ACL repair using an internal brace combined with an anterolateral ligament reconstruction using a gracilis autograft.

Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia.

Nitric oxide (NO)-based therapies effectively inhibit neointimal hyperplasia in animal models of arterial injury and bypass grafting, but are not available clinically. We created a simple, effective, locally applied NO-eluting therapy to prevent restenosis after vascular procedures. We investigated the efficacy of perivascular delivery of two distinctly different diazeniumdiolate NO donors, 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (short half-life) and diazeniumdiolated poly(acrylonitrile) (PAN/NO) (long half-life), in powder or gel form (30% poloxamer 407), at inhibiting neointimal hyperplasia using the rat carotid artery injury model. Two weeks postinjury, all of the NO-eluting therapies successfully reduced neointimal hyperplasia. However, most dramatically, PROLI/NO powder reduced intimal area by 91.2% (p<0.05) versus injury alone. PROLI/NO powder was noted to reduce the medial area (40.2% vs injury alone, p<0.05), whereas other groups showed no such effect. Three days postinjury, each NO treatment group significantly reduced cellular proliferation. However, inflammatory markers revealed a distinct pattern: PAN/NO groups displayed increased leukocyte infiltration (p<0.05), whereas PROLI/NO groups displayed less macrophage infiltration (p<0.05). In conclusion, perivascular delivery of diazeniumdiolate NO donors in powder or gel form effectively inhibits neointimal hyperplasia. Application of short-acting PROLI/NO powder most effectively inhibited neointimal hyperplasia and inflammation and may represent a simple, clinically applicable NO-eluting therapy to prevent neointimal hyperplasia and restenosis after open vascular interventions.

A reproducible porcine ePTFE arterial bypass model for neointimal hyperplasia.

BACKGROUND: Late failure of prosthetic vascular bypass grafting using expanded polytetrafluoroethylene (ePTFE) is secondary to the development of neointimal hyperplasia, most commonly at the distal anastomosis. To develop therapies that can improve upon current prosthetic vascular bypass grafting, a large animal model of prosthetic bypass grafting that results in reproducible neointimal hyperplasia is necessary. METHODS: We performed bilateral end-to-side carotid artery bypasses with 6 mm ePTFE in a porcine model (n = 11). We studied graft patency using magnetic resonance angiography (MRA, 3 wk), duplex ultrasonography (4 wk), and digital-subtraction contrast angiography (4 wk). Animals were sacrificed at 4 wk and morphometric analysis was performed. RESULTS: Of the 11 animals that underwent surgery, one pig died from respiratory compromise; of the remaining 10, graft patency was 90% at 4 wk. Peak systolic and end diastolic velocities were established for this model using ultrasonography. MRA, ultrasonography, and angiography confirmed graft patency and were complimentary tools to evaluate the grafts. Development of neointimal hyperplasia was reproducible at 4 wk in both the proximal and distal anastomoses (2.5 to 3 mm(2)) of the ePTFE bypass grafts. CONCLUSION: We developed a reproducible porcine ePTFE carotid artery bypass model for studying neointimal hyperplasia. Not only does this model allow for the manipulation and evaluation of potential therapies, but patency and neointimal hyperplasia can be easily evaluated by traditional means, such as MRA, ultrasonography, and angiography. This preclinical model is ideal for evaluation of novel therapies in vivo designed to inhibit neointimal hyperplasia following arterial reconstruction with prosthetic bypass grafting.

How to Rapidly Abolish Knee Extension Deficit After Injury or Surgery: A Practice-Changing Video Pearl From the Scientific Anterior Cruciate Ligament Network International (SANTI) Study Group.

Knee extension deficit is frequently observed after anterior cruciate ligament reconstruction or rupture and other acute knee injuries. Loss of terminal extension often occurs because of hamstring contracture and quadriceps inactivation rather than mechanical intra-articular pathology. Failure to regain full extension in the first few weeks after anterior cruciate ligament reconstruction is a recognized risk factor for adverse long-term outcomes, and therefore, it is important to try to address it. In this Technical Note, a simple, rapid, and effective technique to help regain full knee extension and abolish quadriceps activation failure is described.

Accuracy and cost-effectiveness of [18F]-2-fluoro-deoxy-D-glucose-positron emission tomography scan in potentially resectable non-small cell lung cancer.

STUDY OBJECTIVES: This retrospective study of patients who were referred for surgical resection of non-small cell lung cancer (NSCLC) assessed the accuracy and cost-effectiveness of positron emission tomography (PET) with radiolabeled [18F]-2-fluoro-deoxy-D-glucose (FDG) in staging mediastinal lymph nodes (MLNs). DESIGN: From January 2001 to September 2002, 90 patients with suspected or proven NSCLC who had been referred for curative resection were retrospectively reviewed. All patients were without evidence of metastatic disease. Sixty-nine of the 90 patients had undergone thoracic FDG-PET imaging as part of their evaluation and are the focus of this study. Sensitivity, specificity, accuracy, and positive and negative predictive values for metastasis to the MLN were calculated for CT scanning vs FDG-PET scanning. Four algorithms for staging MLN with mediastinoscopy and/or FDG-PET scan were compared. MEASUREMENTS AND RESULTS: Sixty-nine patients underwent preoperative CT and FDG-PET scans, and 32 of 69 patients underwent mediastinoscopy. Fifty-seven patients underwent thoracotomy with complete mediastinal lymphadenectomy. Sensitivity, specificity, accuracy, and positive and negative predictive values for CT scans and FDG-PET scans were 46%, 86%, 78%, 43%, and 87%, and 62%, 98%, 91%, 89% and 92%, respectively. Mediastinoscopy was accurate in 32 of 32 patients (100%). Routine mediastinoscopy remains the most economically reasonable strategy with excellent sensitivity. Selective FDG-PET imaging improved the sensitivity of noninvasive staging for patients with normal MLNs on CT scans. CONCLUSIONS: Selective use of FDG-PET imaging improves staging accuracy compared to CT scanning alone and makes it a cost-effective adjunct to the preoperative staging of NSCLC. However, in patients with adenocarcinoma and MLNs of < 1 cm, FDG-PET scanning cannot yet replace mediastinoscopy.

Low potassium dextran lung preservation solution reduces reactive oxygen species production.

BACKGROUND: Low potassium dextran lung preservation solution has reduced primary graft failure in animal and human studies. Though the mechanism of reducing primary graft failure is unknown, low potassium dextran differs most significantly from solutions such as Euro-Collins (EC) and University of Wisconsin in its potassium concentration. The aim of this study was to investigate the impact that potassium concentration in lung preservation solutions had on pulmonary arterial smooth muscle cell depolarization and production of reactive oxygen species. METHODS: Using isolated pulmonary artery smooth muscle cells from Sprague-Dawley rats, the patch-clamp technique was used to measure resting cellular membrane potential and whole cell potassium current. Measurements were recorded at base line and after exposure to low potassium dextran, EC, and University of Wisconsin solutions. Pulmonary arteries from rats were isolated from the main pulmonary artery to the fourth segmental branch. Arteries were placed into vials containing low potassium dextran, EC, low potassium EC, Celsior, and University of Wisconsin solutions with reactive oxygen species measured by lucigenin-enhanced chemiluminescence. RESULTS: Pulmonary artery smooth muscle cell membrane potentials had a significant depolarization when placed in the University of Wisconsin or EC solutions, with changes probably related to inhibition of voltage-gated potassium channels. Low potassium dextran solution did not alter the membrane potential. Production of reactive oxygen species as measured by chemiluminescence was significantly higher when pulmonary arteries were exposed to University of Wisconsin or EC solutions (51,289 +/- 5,615 and 35,702 +/- 4353 counts/0.1 minute, respectively) compared with low potassium dextran, Celsior, and low potassium EC (12,537 +/- 3623, 13,717 +/- 3,844 and 15,187 +/- 3,792 counts/0.1 minute, respectively). CONCLUSIONS: Preservation solutions with high potassium concentration are clearly able to depolarize the pulmonary artery smooth muscle cells and increase pulmonary artery reactive oxygen species production. Low potassium preservations solutions may limit reactive oxygen species production and thus reduce the incidence of primary graft failure in lung transplantation.

Dysphagia after anterior cervical spine surgery: a systematic review of potential preventative measures.

BACKGROUND CONTEXT: Anterior cervical spine surgery is one of the most common spinal procedures performed around the world, but dysphagia is a frequent postoperative complication. Many factors have been associated with an increased risk of swallowing difficulties, including multilevel surgery, revision surgery, and female gender. PURPOSE: The objective of this study was to review and define potential preventative measures that can decrease the incidence of dysphagia after anterior cervical spine surgery. STUDY DESIGN: This was a systematic literature review. METHODS: A systematic review in the Medline database was performed. Articles related to dysphagia after anterior cervical spine surgery and potential preventative measures were included. RESULTS: Twenty articles met all inclusion and exclusion criteria. These articles reported several potential preventative measures to avoid postoperative dysphagia. Preoperative measures include performing tracheal exercises before the surgical procedure. Intraoperative measures can be summarized as avoiding a prolonged operative time and the use of recombinant human bone morphogenetic protein in routine anterior cervical spine surgery, using small and smoother cervical plates, using anchored spacers instead of plates, application of steroid before wound closure, performing arthroplasty instead of anterior cervical fusion for one-level disease, decreasing tracheal cuff pressure during medial retraction, using specific retractors, and changing the dissection plan. CONCLUSIONS: Current literature supports several preventative measures that may decrease the incidence of postoperative dysphagia. Although the evidence is limited and weak, most of these measures did not appear to increase other complications and can be easily incorporated into a surgical practice, especially in patients who are at high risk for postoperative dysphagia.

Poly(diol-co-citrate)s as novel elastomeric perivascular wraps for the reduction of neointimal hyperplasia.

The synthesis of poly(diol-co-citrate) elastomers that are biocompatible with vascular cells and can modulate the kinetics of the NO release based on the diol of selection is reported. NO-mediated cytostatic or cytotoxic effects can be controlled depending on the NO dose and the exposure time. When implanted in vivo in a rat carotid artery injury model, these materials demonstrate a significant reduction of neointimal hyperplasia. This is the first report of a NO-releasing polymer fabricated in the form of an elastomeric perivascular wrap for the treatment of neointimal hyperplasia. These elastomers also show promise for other cardiovascular pathologies where NO-based therapies could be beneficial.

Nitric oxide and nanotechnology: a novel approach to inhibit neointimal hyperplasia.

OBJECTIVE: Nitric oxide (NO) has been shown to inhibit neointimal hyperplasia after arterial interventions in several animal models. To date, however, NO-based therapies have not been used in the clinical arena. Our objective was to combine nanofiber delivery vehicles with NO chemistry to create a novel, more potent NO-releasing therapy that can be used clinically. Thus, the aim of this study was to evaluate the perivascular application of spontaneously self-assembling NO-releasing nanofiber gels. Our hypothesis was that this application would prevent neointimal hyperplasia. METHODS: Gels consisted of a peptide amphiphile, heparin, and a diazeniumdiolate NO donor (1-[N-(3-Aminopropyl)-N-(3-ammoniopropyl)]diazen-1-ium-1,2-diolate [DPTA/NO] or disodium 1-[(2-Carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate [PROLI/NO]). Nitric oxide release from the gels was evaluated by the Griess reaction, and scanning electron microscopy confirmed nanofiber formation. Vascular smooth muscle cell (VSMC) proliferation and cell death were assessed in vitro by (3)H-thymidine incorporation and Personal Cell Analysis (PCA) system (Guava Technologies, Hayward, Calif). For the in vivo work, gels were modified by reducing the free-water content. Neointimal hyperplasia after periadventitial gel application was evaluated using the rat carotid artery injury model at 14 days (n = 6 per group). Inflammation and proliferation were examined in vivo with immunofluorescent staining against CD45, ED1, and Ki67 at 3 days (n = 2 per group), and graded by blinded observers. Endothelialization was assessed by Evans blue injection at 7 days (n = 3 per group). RESULTS: Both DPTA/NO and PROLI/NO, combined with the peptide amphiphile and heparin, formed nanofiber gels and released NO for 4 days. In vitro, DPTA/NO inhibited VSMC proliferation and induced cell death to a greater extent than PROLI/NO. However, the DPTA/NO nanofiber gel only reduced neointimal hyperplasia by 45% (intima/media [I/M] area ratio, 0.45 +/- 0.07), whereas the PROLI/NO nanofiber gel reduced neointimal hyperplasia by 77% (I/M area ratio, 0.19 +/- 0.03, P < .05) vs control (injury alone I/M area ratio, 0.83 +/- 0.07; P < .05). Both DPTA/NO and PROLI/NO nanofiber gels significantly inhibited proliferation in vivo (1.06 +/- 0.30 and 0.19 +/- 0.11 vs injury alone, 2.02 +/- 0.20, P < .05), yet had minimal effect on apoptosis. Only the PROLI/NO nanofiber gel inhibited inflammation (monocytes and leukocytes). Both NO-releasing nanofiber gels stimulated re-endothelialization. CONCLUSIONS: Perivascular application of NO-releasing self-assembling nanofiber gels is an effective and simple therapy to prevent neointimal hyperplasia after arterial injury. Our study demonstrates that the PROLI/NO nanofiber gel most effectively prevented neointimal hyperplasia and resulted in less inflammation than the DPTA/NO nanofiber gel. This therapy has great clinical potential to prevent neointimal hyperplasia after open vascular interventions in patients.

Increased release of serotonin from rat ileum due to dexfenfluramine.

Plasma levels of serotonin are elevated in primary pulmonary hypertension even after bilateral lung transplantation, suggesting a possible etiologic role. Serotonin is released primarily from the small intestine. Anorectic agents, such as dexfenfluramine, which can cause pulmonary hypertension, are known to inhibit potassium channels in vascular smooth muscle cells. We examined the hypothesis that dexfenfluramine may stimulate release of serotonin from the ileum by inhibition of K+ channels. In an isolated loop of rat ileum perfused with a physiological salt solution, the administration of dexfenfluramine, its major metabolite D-norfenfluramine, the potassium channel blocker 4-aminopyridine (5 mM), and caffeine (30 mM) increased serotonin levels in the venous effluent. Potassium chloride (60 mM) tended to increase serotonin levels. In genetically susceptible individuals, dexfenfluramine may induce pulmonary hypertension by increasing cytosolic calcium in enterochromaffin cells of the small intestine, thus releasing serotonin and causing vasoconstriction. This work indicates that dexfenfluramine and its major metabolite d-norfenfluramine can increase serotonin release from the small intestine.