Five-Year Management of Vascular Injuries of the Extremities in the "Real-World" Setting in Northeastern Greece: The Role of Iatrogenic Traumas.

BACKGROUND: Vascular trauma comprises a diagnostic and surgical challenge. Aim of this study was to present the vascular traumas treated in our Tertiary Hospital during the last 5 years. METHODS: We retrospectively reviewed the surgical records of our vascular department and documented the site and type of vascular injuries of the extremities along with the concurrence of musculoskeletal injuries. The type and outcome of surgical interventions were also recorded. RESULTS: Fifty-eight cases of vascular trauma were recorded (39 in the upper and 19 in the lower extremities). Overall, iatrogenic traumas accounted for 41.3% of cases. The arterial injuries of the upper limb were blunt and penetrating in 27% and 67%, respectively. The most affected artery in the upper limb was the radial artery (37.8%), followed by the ulnar artery (27%) and the brachial artery (24.3%). Orthopedic injuries were recorded in 19% of patients. Management involved simple revascularization, bypass operations, patch arterioplasty and endovascular management in 48.7%, 33.3%, 5.1%, and 5.1%, respectively. The most affected site in the lower extremity was the common femoral artery (36.8%) followed by the popliteal artery (21%). Bone fractures were reported in 5 cases (26.3%). The surgical management involved bypass, simple revascularization, patch arterioplasty in 42.1%, 26.3%, and 21%, respectively. Endovascular management was performed in 10.5%. CONCLUSIONS: A considerable percentage of iatrogenic vascular injuries was recorded, affecting both the upper and lower limbs. Despite the trend toward centralization of vascular services, a basic service of vascular surgery should be available in most sites to ensure that patients with vascular injuries receive fast and appropriate care.

Fufang-Zhenzhu-Tiaozhi capsule ameliorates rabbit's iliac artery restenosis by regulating adiponectin signaling pathway.

BACKGROUND AND PURPOSE: Fufang-Zhenzhu-Tiaozhi Capsule (FTZ), a traditional Chinese medicine, has been shown obvious effects on the treatment of dyslipidemia and atherosclerosis. The aim of this study was to evaluate whether FTZ can ameliorate rabbit iliac artery restenosis after angioplasty by regulating adiponectin signaling pathway. EXPERIMENTAL APPROACH: The rabbit iliac artery restenosis model was established through percutaneous iliac artery transluminal balloon angioplasty and a high-fat diet. Twenty eight male New Zealand rabbits (8-week-old) were divided into sham operation group (Group Ⅰ), model group (Group Ⅱ), atorvastatin group (Group Ⅲ) and FTZ group (Group Ⅳ), with 7 rabbits in each group. Vascular stenosis was analyzed with Digital Subtraction Angiography. Level of adiponectin (APN), and inflammatory factor including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) as well as monocyte chemoattractant protein-1 (MCP-1) was measured by Enzyme Linked Immunosorbent Assay; and injured iliac artery was collected for Hematoxylin-eosin staining and Western Blotting detection of expression of peroxisome proliferator-activated receptor-alpha (PPAR-α), adenosine 5'-monophosphate -activated protein kinase (AMPK) and phosphorylated adenosine 5'-monophosphate -activated protein kinase (p-AMPK). Besides, we evaluated FTZ's safety for the first time. KEY RESULTS: Percutaneous iliac artery transluminal balloon angioplasty and high-fat diet result in inflammatory response and restenosis. Compared with Group Ⅱ, iliac artery restenosis was significantly ameliorated in Group Ⅳ (P < 0.05). Treated with FTZ, serum lipids were significantly decreased (P < 0.01), while the level of APN was elevated significantly (P < 0.01). Western blotting detection of the injured iliac artery showed that the expressions of PPAR-α, AMPK and p-AMPK were significantly increased in Group Ⅳ (P < 0.01) than that in Group Ⅱ. Besides, before and after taking drugs, liver and kidney function indicators, creatine kinase, as well as measurement of echocardiography were of no statistical difference in four groups(P > 0.05). CONCLUSIONS AND IMPLICATIONS: FTZ could effectively reduce serum lipids and ameliorate rabbit's iliac artery restenosis after angioplasty, and its mechanism may be related to activation of APN signaling pathway.

Ultrasound Guidance Enhances the Efficiency of Brachial Plexus Block and Ameliorates the Vascular Injury Compared with Nerve Stimulator Guidance in Hand Surgery Patients.

Background: Nerve stimulation guidance and ultrasound guidance are two major methods that have been widely accepted and applied in axillary brachial plexus block. However, the differences between the effects of these two types of guidance still need to be further elucidated for clinical usage. Materials and Methods: Overall, 208 patients undergoing elective upper limb surgeries and receiving axillary brachial plexus block were recruited in our study. The patients were randomly assigned to receive either ultrasound guidance (group U, n = 112) or nerve stimulation (group N, n = 96). Pinprick test was performed for assessing the sensory blockades. The pain was evaluated by visual analog scale (VAS). Reactive oxygen species (ROS) levels were measured by dichloro-dihydro-fluorescein diacetate staining and serum levels of nitric oxide (NO), nitric oxide synthases (NOS), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein 1 (MCP1) were evaluated by ELISA. Results: Ultrasound guidance significantly enhanced the quality of the sensory blockade and reduced the VAS scores when compared with the nerve stimulator guidance. In addition, the production of ROS, NO, NOS, TNF-α, and MCP-1 were significantly alleviated by ultrasound guidance. Conclusion: Ultrasound-guided brachial plexus block relieves pain during operation, provides higher success rates in the nerve block, causes less vascular damage and results in lower levels of inflammatory cytokines secretion when compared with neurostimulator-directed brachial plexus blockage.

Danhong injection mobilizes endothelial progenitor cells to repair vascular endothelium injury via upregulating the expression of Akt, eNOS and MMP-9.

BACKGROUD: Endothelial progenitor cells (EPCs) have been characterized as one of the key effectors of endothelial healing. The effect of Danhong injection (DHI), the most widely prescribed Chinese medicine for coronary heart disease (CHD), on EPCs mobilization remains unclear. PURPOSE: We aimed to assess the effect of DHI on EPCs mobilization to repair percutaneous coronary intervention (PCI) induced vascular injury, and to investigate the characteristics and potential mechanism of DHI on EPCs mobilization. METHOD: Forty-two patients with CHD underwent PCI and received stent implantation were enrolled in a Phase II clinical trials. All patients received routine western medical treatment after PCI, patients of DHI group received DHI in addition. The levels of CECs, cytokines (vWF, IL-6, CRP) and EPCs were analyzed at baseline, post-PCI and after treatment. To investigate the characteristics of DHI on EPCs mobilization, 12 healthy volunteers received intravenous infusion of DHI once and the other 12 received for 7 days. EPCs enumeration were done at a series of time points. At last we tested the effect of DHI and three chemical constituents of DHI (danshensu; lithospermic acid, LA; salvianolic acid D, SaD) on EPCs level and expression of Akt, eNOS and MMP-9 in bone marrow cells of myocardial infarction (MI) mice. RESULTS: In the DHI group the angina symptoms were improved, the levels of cytokines and CECs were reduced; while EPCs population was increased after treatment. In the phase I clinical trials, EPCs counts reached a plateau phase in 9 h and maintained for more than 10 h after a single dose. After continuous administration, EPCs levels plateaued on the 3rd or 4th day, and maintain till 1 day after the withdrawal, then its levels gradually declined. DHI treatment induced a timely dependent mobilization of EPCs. DHI promoted EPCs mobilization via upregulating the expression of Akt, eNOS and MMP-9 in BM. LA and SaD have played a valuable role in EPCs mobilization. CONCLUSION: These initial results demonstrated that DHI is effective in alleviating endothelial injury and promoting endothelial repair through enhancing EPCs mobilization and revealed the effect feature and possible mechanisms of DHI in mobilizing EPCs.

Rate of acquired pulmonary vein stenosis after ablation of atrial fibrillation referred to electroanatomical mapping systems: Does it matter?

BACKGROUND: Thermal injury during radiofrequency ablation (RFA) of atrial fibrillation (AF) can lead to pulmonary vein stenosis (PVS). It is currently unclear if routine screening for PVS by imaging (echocardiography, computed tomography) is clinically meaningful and if there is a correlation between PVS and the electroanatomical mapping system (EAMS) used for the ablation procedure. It was therefore investigated in the current single center experience. METHODS: All patients from January 2004 to December 2016 with the diagnosis of PVS after interventional ablation of AF by radiofrequency were retrospectively analyzed. From 2004 to 2007, transesophageal echocardiography was routinely performed as screening for RFA-acquired PVS (group A). Since 2008, diagnostics were only initiated in cases of clinical symptoms suggestive for PVS (group B). RESULTS: The overall PVS rate after interventional RFA for AF of the documented institution is 0.72% (70/9754). The incidence was not influenced by screening: group A had a 0.74% PVS rate and group B a 0.72% rate (NS). Referred to as the EAMS, there were significant differences: 20/4229 (0.5%) using CARTO®, 48/4510 (1.1%) using EnSite®, 1/853 (0.1%) using MediGuide®, and 1/162 (0.6%) using Rhythmia®. Since 2009, no significant difference between technologies was found. CONCLUSIONS: The present analysis of 9754 procedures revealed 70 cases of PVS. The incidence of PVS is not related to screening but to the application of different EAMS. Possible explanations are technological backgrounds (magnetic vs. electrical), learning curves, operator experience, and work-flow differences. Furthermore, incorporation of new technologies seems to be associated with higher incidences of PVS before workflows are optimized.

Hyperhomocysteinaemia and vascular injury: advances in mechanisms and drug targets.

Homocysteine is a sulphur-containing non-proteinogenic amino acid. Hyperhomocysteinaemia (HHcy), the pathogenic elevation of plasma homocysteine as a result of an imbalance of its metabolism, is an independent risk factor for various vascular diseases, such as atherosclerosis, hypertension, vascular calcification and aneurysm. Treatments aimed at lowering plasma homocysteine via dietary supplementation with folic acids and vitamin B are more effective in preventing vascular disease where the population has a normally low folate consumption than in areas with higher dietary folate. To date, the mechanisms of HHcy-induced vascular injury are not fully understood. HHcy increases oxidative stress and its downstream signalling pathways, resulting in vascular inflammation. HHcy also causes vascular injury via endoplasmic reticulum stress. Moreover, HHcy up-regulates pathogenic genes and down-regulates protective genes via DNA demethylation and methylation respectively. Homocysteinylation of proteins induced by homocysteine also contributes to vascular injury by modulating intracellular redox state and altering protein function. Furthermore, HHcy-induced vascular injury leads to neuronal damage and disease. Also, an HHcy-activated sympathetic system and HHcy-injured adipose tissue also cause vascular injury, thus demonstrating the interactions between the organs injured by HHcy. Here, we have summarized the recent developments in the mechanisms of HHcy-induced vascular injury, which are further considered as potential therapeutic targets in this condition. LINKED ARTICLES: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Upper Limb Ischemia by Subclavian Artery Dissection after Osteopathic Manipulation.

We report the case of a young woman who experienced ischemia of upper limb after osteopathic manipulation. Duplex and computed tomography scan showed wall hematoma of the ostium of subclavian artery. The patient spontaneously recovered so that no surgery was necessary. Dissection of vertebral and carotid arteries has been reported after osteopathic manipulations. We report ischemia of upper limb secondary to dissection of subclavian artery. Arterial dissections associated with manipulation should be recorded in a register in order to assess more carefully the vascular risk that this method carries.

Trichosanthin attenuates vascular injury-induced neointimal hyperplasia following balloon catheter injury in rats.

Trichosanthin (TCS), isolated from the root tuber of Trichosantheskirilowii, a well-known traditional Chinese medicinal plant, belonging to the Cucurbitaceae family, was found to exhibit numerous biological and pharmacological activities including anti-inflammatory. However, the effects of TCS on arterial injury induced neointimal hyperplasia and inflammatory cell infiltration remains poorly understood. The aim of study was to examine the effectiveness of TCS on arterial injury-mediated inflammatory processes and underlying mechanisms. A balloon-injured carotid artery induced injury in vivo in rats was established as a model of vascular injury. After 1 day TCS at 20, 40, or 80 mg/kg/day was administered intraperitoneally, daily for 14 days. Subsequently, the carotid artery was excised and taken for immunohistochemical staining. Data showed that TCS significantly dose-dependently reduced balloon injury-induced neointima formation in the carotid artery model rat, accompanied by markedly decreased positive expression percentage proliferating cell nuclear antigen (PCNA). In the in vitro study vascular smooth muscle cells (VSMC) were cultured, proliferation stimulated with platelet-derived growth factor-BB (PDGF-BB) (20 ng/ml) and TCS at 1, 2, or 4 µM added. Data demonstrated that TCS inhibited proliferation and cell cycle progression of VSMC induced by PDGF-BB. Further, TCS significantly lowered mRNA expression of cyclinD1, cyclinE1, and c-fos, and protein expression levels of Akt1, Akt2, and mitogen-activated protein kinase MAPK (ERK1) signaling pathway mediated by PDGF-BB. These findings indicate that TCS inhibits vascular neointimal hyperplasia induced by vascular injury in rats by suppression of VSMC proliferation and migration, which may involve inhibition of Akt/MAPK/ERK signal pathway.

Resolution of vascular injury: Specialized lipid mediators and their evolving therapeutic implications.

Acute vascular injury occurs in a number of important clinical contexts, including spontaneous disease-related events (e.g. plaque rupture, thrombosis) and therapeutic interventions such as angioplasty, stenting, or bypass surgery. Endothelial cell (EC) disruption exposes the underlying matrix, leading to a rapid deposition of platelets, coagulation proteins, and leukocytes. A thrombo-inflammatory response ensues characterized by leukocyte recruitment, vascular smooth muscle cell (VSMC) activation, and the elaboration of cytokines, reactive oxygen species and growth factors within the vessel wall. A resolution phase of vascular injury may be described in which leukocyte efflux, clearance of debris, and re-endothelialization occurs. VSMC migration and proliferation leads to the development of a thickened neointima that may lead to lumen compromise. Subsequent remodeling involves matrix protein deposition, and return of EC and VSMC to quiescence. Recent studies suggest that specialized pro-resolving lipid mediators (SPM) modulate key aspects of this response, and may constitute an endogenous homeostatic pathway in the vasculature. SPM exert direct effects on vascular cells that counteract inflammatory signals, reduce leukocyte adhesion, and inhibit VSMC migration and proliferation. These effects appear to be largely G-protein coupled receptor-dependent. Across a range of animal models of vascular injury, including balloon angioplasty, bypass grafting, and experimental aneurysm formation, SPM accelerate repair and reduce lesion formation. With bioactivity in the pM-nM range, a lack of discernible cytotoxicity, and a spectrum of vasculo-protective properties, SPM represent a novel class of vascular therapeutics. This review summarizes current research in this field, including a consideration of critical next steps and challenges in translation.

Traumatic Anterior Knee Dislocation with Popliteal Artery Injury: The Importance of a Prompt Diagnosis and Treatment to Obtain Lower Limb Salvage.

We report a case of traumatic anterior dislocation of the left knee in association with disruption of the soft tissues including knee ligaments, popliteal artery, and common peroneal nerve, resulting in lower limb acute ischemia. All components of this complex trauma were recognized and treated promptly. First, he was submitted to closed reduction of the dislocated knee under general anesthesia; right after he underwent superficial femoro-tibioperoneal trunk bypass using a reversed saphenous contralateral vein recurring to a posterior approach through a popliteal S-shaped incision; rehabilitation program was initiated early; a second and final reconstructive orthopedic operation was carried out in a different center. The present case is important in 2 aspects. First, it reports a very rare occurrence of simultaneous anterior dislocation of the knee associated with vascular insult and common peroneal nerve injury, which was rarely reported in the current literature; second, it highlights that with timely intervention and a team approach, excellent results could be achieved.

Management of Vascular Trauma during the Paris Terrorist Attack of November 13, 2015.

BACKGROUND: On November 13, 2015, Paris and Saint-Denis were the targets of terrorist attacks. The Public Hospitals of Paris Organization and the Percy Armed Forces Instruction Hospitals were mobilized to face the mass casualty situation. The objective of this study is to analyze the management of the victims presenting with a nonthoracic vascular trauma (NTVT). METHODS: All the data relating to the victims of NTVT who required a specific vascular open or endovascular treatment were analyzed retrospectively. A 6-month follow-up was obtained for all the patients. RESULTS: Among the 351 wounded, 20 (5.7%) patients had an NTVT and were dispatched in 8 hospitals (11 men of average age 32). NTVTs were gunshots in 17 cases (85%) or due to a handmade bomb in 3 cases (15%). Twelve patients (60%) received cardiopulmonary resuscitation during prehospital care. NTVT affected the limbs (14 cases, 70%) and the abdomen or the small pelvis (6 cases, 30%). All the patients were operated in emergency. Arterial lesions were treated with greater saphenous vein bypasses, by ligation, and/or embolization. Eleven venous lesions were treated by direct repair or ligation. Associated lesions requiring a specific treatment were present in 19 patients (95%) and were primarily osseous, nervous, and abdomino-pelvic. Severe postoperative complications were observed in 9 patients (45%). Fourteen patients (70%) required blood transfusion (6.4 U of packed red blood cells on average, range 0-48). There were no deaths or amputation and all vascular reconstructions were patent at 6 months. CONCLUSIONS: The effectiveness of the prehospital emergency services and a multisite and multidisciplinary management made it possible to obtain satisfactory results for NTVT casualties. All the departments of vascular surgery must be prepared to receive many wounded victims in the event of terrorist attacks.

Wireless Ultrasound Guidance for Femoral Venous Cannulation in Electrophysiology: Impact on Safety, Efficacy, and Procedural Delay.

BACKGROUND: Ultrasound (US) guidance increases safety and efficacy in vascular cannulation and is considered the standard of care. However, barriers including workflow interference and the need to be assisted by a second operator limit its adoption in clinical routine. The use of wireless US (WUS) may overcome these barriers. The aim of this study was to assess the impact of a novel WUS probe during its initial implantation in an electrophysiology (EP) laboratory. METHODS: Thirty-six patients requiring femoral venous cannulation for EP procedures were included in this single center, prospective, observational study, comparing WUS guidance with the anatomical landmark approach. The primary endpoint was time to successful cannulation. Secondary endpoints included rate of unsuccessful punctures, accidental arterial punctures, and workflow interference. RESULTS: Compared with anatomical landmark approach, WUS guidance significantly reduced mean time to successful cannulation (87.3 ± 94.3 vs 238.1 ± 294.7 seconds, P < 0.01). Workflow interference was predominantly nonexistent or mild and decreased after the first three weeks of use. In addition, WUS guidance improved safety and efficacy, reducing the rate of accidental arterial punctures (0.02 ± 0.1 vs 0.25 ± 0.5 arterial punctures per cannulation, P < 0.05) and unsuccessful attempts (0.26 ± 0.8 vs 1.75 ± 2.1 attempts per cannulation, P < 0.01). CONCLUSIONS: WUS guidance resulted in faster, safer, and more effective femoral venous cannulation than the anatomical landmark approach without adding significant workflow interference. The application of wireless technology in this setting contributed to overcoming some of the barriers preventing a more widespread clinical use of US guidance.

Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients.

OBJECTIVES: Food or supplement-derived L-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral L-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue. METHODS: Thirty-one HD patients with carnitine deficiency were treated with oral L-carnitine (900 mg/d) for 6 months. At baseline and after treatment, clinical variables including circulating levels of carnitine fractions, TMA, TMAO, advanced glycation end products (AGE), soluble forms of intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and malondialdehyde (MDA) were measured. RESULTS: Oral L-carnitine supplementation significantly increased total, free, acyl carnitine, and plasma TMA and TMAO levels, whereas it decreased markers of vascular injury and oxidative stress such as sICAM-1, sVCAM-1, and MDA levels. TMA and TMAO levels at baseline were correlated with each other, and free carnitine was independently associated with TMAO levels. Furthermore, change in AGE values from baseline ([INCREMENT]AGE) was positively correlated with [INCREMENT]sICAM-1 (P = 0.043) and was a sole independent determinant of [INCREMENT]sICAM-1 (R = 0.133, P = 0.043). CONCLUSIONS: This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.

Ventricular arrhythmias near the distal great cardiac vein: challenging arrhythmia for ablation.

BACKGROUND: Catheter ablation for ventricular arrhythmia (VA) near the distal great cardiac vein (GCV) is often challenging, and data are limited. METHODS AND RESULTS: Analysis was performed in 30 patients (19 men; age, 52.8±15.5 years) who underwent catheter ablation for focal VA (11 ventricular tachycardia and 19 premature contractions) with early activation in the GCV (36.7±8.0 ms pre-QRS). Angiography in 27 patients showed earliest GCV site within 5 mm of a coronary artery in 20 (74%). Ablation was performed in the GCV in 15 patients and abolished VA in 8. Ablation was attempted at adjacent non-GCV sites in 19 patients and abolished VA in 5 patients (4 from the left ventricular endocardium and 1 from the left coronary cusp); all success had VA with an initial r wave in lead I and activation ≤7 ms after the GCV (GCV-non-GCV interval). In 13 patients, percutaneous epicardial mapping was performed, but because of adjacent coronaries only 2 received radiofrequency application with VA elimination in 1. Surgical cryoablation was performed in 3 patients and abolished VA in 2. Overall acute success was achieved in 16 (53%) patients. After a median of 2.8 months, 13 patients remained free of VA. Major complications occurred in 4 patients, including coronary injury requiring stenting. CONCLUSIONS: Ablation for this arrhythmia is challenging and often limited by the adjacent coronary vessels. Success of anatomically guided endocardial ablation may be identified by a short GCV-non-GCV interval and r wave in lead I.

Vascular injuries caused by acupuncture. A systematic review.

AIM: The aim of the study was to systematically review the literature on vascular injuries caused by acupuncture. METHODS: This was a systematic literature search in Medline and PubMed. RESULTS: Thirty-one cases were identified and the majority developed symptoms in direct connection with the acupuncture treatment. Three patients died, two from pericardial tamponade and one from an aortoduodenal fistula. There were seven more tamponades, eight pseudoaneurysms, two with ischemia, two with venous thrombosis, one with compartment syndrome and seven with bleeding (five in the central nervous system). The two patients with ischemia had remaining sequeleae. Information on follow-up was suboptimal with no information in fourteen patients. CONCLUSION: Vascular injuries are rare, bleeding and pseudoaneurysm dominating. Follow-up is insufficient in the hitherto published papers.

Hyperbaric oxygen effect on MMP-9 after a vascular insult.

Matrix metalloproteinease-9 (MMP-9) is involved in a host of processes. Many of its processes are physiologically beneficial as well as detrimental. The over-expression of this enzyme has been implicated as a contributory factor to some of the sequalae associated with cerebral ischemia, cell death, non-healing wounds, traumatic brain injury, aneurysms, and plaque instability in atherosclerosis. Several studies have examined the effect of hyperbaric oxygen (HBO) on MMP-9 expression. Because this proteinase is involved in both chronic and acute pathology, we wanted to investigate an acute expression model and see if, and how quickly, its expression would respond to HBO therapy. Our patient was scheduled to have elective surgery with an overnight stay followed by a series of HBO exposures. The patient served as her own control. An MMP-9 and urine pH was obtained prior to surgery to establish a baseline. On days 1, 3, and 4 post-op, samples were obtained before and after hyperbaric exposure. The patient was exposed to 100% O2 at 2.5 ATA for 60 min during each treatment for 5 days. The patient's MMP-9 values were dramatically elevated after surgery as compared to the baseline readings. The percentage increase from baseline was 400%. Our patient showed a significant reduction in MMP-9 expression after each hyperbaric exposure with the greatest decrease seen on post-op day 1 and subsequent exposures showing slightly less expression. Reduction in MMP-9 expression ranged from 46% on day 1 to 30% on post-op day 4. This case study suggests that if done relatively soon after a vascular or tissue insult, HBO can reduce MMP-9 expression. Chronic vascular pathologies, such as atherosclerotic plaque and aneurysms where over-expression of MMP-9 may result in acute coronary syndrome (ACS) or cerebral vascular accidents (CVAs), may be mitigated by a series of HBO treatments that reduce MMP-9 expression. Causality and/or contributory effects of MMP-9 expression in both pathologic and physiologic processes needs to be further elucidated. The understanding of how HBO therapy modulates these may provide an additional insight into mechanisms and future potential therapies for pathologic conditions such as those described above.

Modulatory effects of seabuckthorn (Hippophae rhamnoides L.) in hypobaric hypoxia induced cerebral vascular injury.

Cerebral edema caused by vascular leakage is a major problem in various injuries of the CNS, such as stroke, head injury and high-altitude illness. A common feature of all these disorders is the fact that they are associated with tissue hypoxia. Hypoxia has been suggested to be a major pathogenic factor for the induction of vascular leakage in the brain. The objective of the present study was to evaluate potential of seabuckthorn (SBT) (Hippophae rhamnoides L.) seed oil in curtailing hypoxia induced transvascular fluid leakage in brain of hypoxia-exposed rats. Exposure of animals to hypobaric hypoxia (9144 m, 5h) caused a significant increase in the transvascular leakage studied by measuring water content and leakage of sodium fluorescein dye in the brain. Hypoxic stress also significantly enhanced the oxidative stress markers such as free radicals and malondialdehyde and it accompanied with decreased levels of antioxidants such as glutathione, glutathione peroxidase and superoxide dismutase. Pretreatment of animals with SBT seed oil significantly restricted the hypoxia induced increase in fluorescein dye leakage suggesting protection against hypoxia induced transvascular leakage in the brain. Hypoxia induced increase in the levels of free radicals and malondialdehyde were significantly lowered after SBT pretreatment. The SBT seed oil pretreatment also resulted in the significantly improved hypoxic tolerance as evidenced by increased hypoxic gasping time and survival time and decreased plasma catecholamine levels, as compared to hypoxic animals. These observations suggest that SBT seed oil possesses significant hypoxia protection activity and curtailed hypoxia induced enhanced vascular leakage in the brain.