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Sample records for critical limb-threatening ischemia

  1. Therapeutic Angiogenesis in Critical Limb Ischemia

    PubMed Central

    Ouma, Geoffrey O.; Zafrir, Barak; Mohler, Emile R.; Flugelman, Moshe Y.

    2013-01-01

    Critical limb ischemia (CLI) is a severe form of peripheral artery disease associated with high morbidity and mortality. The primary therapeutic goals in treating CLI are to reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputation, and improve quality of life (QoL) and survival. These goals may be achieved by medical therapy, endovascular intervention, open surgery, or amputation and require a multidisciplinary approach including pain management, wound care, risk factors reduction, and treatment of comorbidities. No-option patients are potential candidates for the novel angiogenic therapies. The application of genetic, molecular, and cellular-based modalities, the so-called therapeutic angiogenesis, in the treatment of arterial obstructive diseases has not shown consistent efficacy. This article summarizes the current status related to the management of patients with CLI and discusses the current findings of the emerging modalities for therapeutic angiogenesis. PMID:23129733

  2. Tibial intervention for critical limb ischemia.

    PubMed

    Wiechmann, Bret N

    2009-12-01

    Diagnosis and treatment of critical limb ischemia (CLI) is increasingly important as the average age of the world population and the incidence of diabetes and metabolic syndrome increases. Fortunately, most patients will not progress to this stage of peripheral arterial disease, yet if left untreated, there is a high risk of future cardiovascular events. At the point of ischemic rest pain or tissue loss, there are significant implications for morbidity and mortality. There is a high prevalence of multisegment occlusive disease in the CLI patient with the infrapopliteal vessels frequently involved. Revascularization of the affected limb is of utmost importance as the prospects of wound healing and relief of ischemic rest pain are poor without reestablishing continuous flow to the distal extremity. With the advent of endovascular devices designed to treat this vexing problem, the ability to successfully treat this difficult patient population with less procedural morbidity has been greatly enhanced. PMID:21326541

  3. Therapeutic angiogenesis for critical limb ischemia.

    PubMed

    Ko, Sae Hee; Bandyk, Dennis F

    2014-03-01

    The application of gene- and cell-based therapies to promote angiogenesis is a novel concept to treat lower-limb critical limb ischemia (CLI) and may provide an unmet need for patients with no options for revascularization. Proof of concept was demonstrated in animal models resulting in clinical trials that have confirmed the feasibility and short-term efficacy of intramuscular injection of angiogenetic tissue growth factors or bone marrow stem cells. The safety of these biologic therapies has been demonstrated in randomized clinical trials with no "off-target" angiogenesis, growth of occult tumors, or progression of diabetic retinopathy. Current phase III randomized clinical trials using a DNA plasmid with the hepatocyte growth factor gene or bone marrow aspirate concentrate of mesenchymal cells are designed to address several crucial issues, including proper patient selection criteria, relevant clinical endpoints, and long-term efficacy. Because effectiveness of these novel therapies remains to be established, ongoing and future randomized clinical trials should be placebo-controlled, investigator-blinded, and have amputation-free survival as the primary endpoint. Further development of efficient gene transfer techniques and keeping transplanted stem cells healthy have the potential to make biologic therapies more robust in promoting angiogenesis, tissue regeneration, and resolution of CLI symptoms. If sustained efficacy can be demonstrated, new therapeutic strategies for patients with CLI will be available for clinicians, ie, limb revascularization using angiogenic gene or stem cell therapy alone, or in conjunction with endovascular intervention. PMID:25812756

  4. Intraarterial Infusion Therapy via a Subcutaneous Port for Limb-Threatening Ischemia: A Pilot Study

    SciTech Connect

    Strecker, Ernst-Peter K.; Ostheim-Dzerowycz, Wladimir; Boos, Irene B.L.

    1998-03-15

    Purpose: To present the initial results of a new percutaneously implantable catheter port system (PIPS) used for long-term intraarterial infusion therapy in patients with severe ischemic limb disease. Methods: Ten patients with deep, extended ischemic ulcerations (all 10) and osteomyelitis (6/10) of the foot received intraarterial infusions of prostaglandine E{sub 1} and antibiotics, if indicated, via a new port catheter system with the port placed subcutaneously above the groin after percutaneous introduction and the catheter tip placed into the superficial or deep femoral artery. Results: Port implantation and repeated port access were uncomplicated. During the follow-up period (mean 11 months, range 1 week-50 months), port migration, leakage, or infection was not observed. Three catheters thrombosed and were opened by fibrinolysis with recombinant tissue plasminogen activator instilled via the port. Treatment success was achieved in 8 patients: relief from rest pain (8 patients), reduction of ulcer size (4/8), and complete healing (4/8). Limb savage rate was 80%. In 2 patients amputation could not be avoided. Conclusion: Selective long-term arterial infusion therapy presents a valuable therapeutic regimen for limb salvage. With the new catheter port system, repeated local intraarterial infusion is safe and simple.

  5. Isolated Limb Infusion for Limb Salvage in Limb Threatening Extremity Sarcomas

    PubMed Central

    Vohra, Nasreen A.; Turaga, Kiran K.; Gonzalez, Ricardo J.; Conley, Anthony; Reed, Damon; Bui, Marilyn M.; Cheong, David; Letson, Douglas G.; Zager, Jonathan S.

    2015-01-01

    Background Locally advanced, limb threatening soft tissue sarcomas (STS) pose a significant treatment challenge. We report our experience using isolated limb infusion (ILI) in patients with unresectable extremity STS. Methods Twenty-two patients with extremity STS underwent 26 ILIs with melphalan and dactinomycin. Patient characteristics, intra-operative parameters and toxicity were recorded. Outcome measures included limb-salvage and in-field response rates. Results Of the 19 lower and 7 upper extremity ILIs, Wieberdink grade III toxicity or less was observed in all. Median follow up was 11 months. Seventeen patients were evaluable at 3 months post ILI with an overall response rate of 42%. Four (24%) had complete response (CR), 3 (18%) partial response (PR), 3 (18%) stable disease (SD) and 7 (41%) progressive disease (PD). Twelve of 17 (71%) underwent successful limb preservation at a median of 9 months post ILI. Two (12%) were downstaged to resectable disease and remain NED after surgery at 30 and 22 months post ILI. Conclusions ILI is an attractive modality that provides regional disease control and limb preservation in patients with limb threatening sarcoma. Although short term results appear encouraging, long term follow up is needed to fully assess the role of ILI in unresectable extremity STS. PMID:23205633

  6. Long-Term Results of Treatment for Critical Limb Ischemia

    PubMed Central

    Suhara, Masamitsu; Nemoto, Yoko; Shirasu, Takuro; Haga, Makoto; Mochizuki, Yasuaki; Matsukura, Mitsuru; Akai, Takafumi; Taniguchi, Ryosuke; Nemoto, Masaru; Yamamoto, Satoshi; Nishiyama, Ayako; Hosaka, Akihiro; Hoshina, Katsuyuki; Okamoto, Hiroyuki; Shigematsu, Kunihiro; Miyata, Tetsuro; Watanabe, Toshiaki

    2015-01-01

    From 2001 to 2012, arterial reconstruction was performed in 306 out of 497 limbs (62%) with critical limb ischemia. The reasons for non-vascularization include high operative risk (36%), extended necrosis or infection (20%), and technical issues (15%). Cumulative patency and limb salvage in collagen disease were significantly worse compared to arteriosclerosis obliterans. Cumulative limb salvage, amputation free survival (AFS), and major adverse limb event and perioperative death (MALE + POD) in patients with end-stage renal disease (ESRD) were significantly worse compared to patients without ESRD, but not significant with regards to graft patency. Our finding suggests that aggressive arterial reconstruction provides satisfactory long-term results in critical limb ischemia so long as case selection for revascularization is properly made. (This article is a translation of J Jpn Coll Angiol 2014; 54: 5–11.) PMID:26421066

  7. Beperminogene perplasmid for the treatment of critical limb ischemia.

    PubMed

    Suda, Hiroyuki; Murakami, Akihiko; Kaga, Toshihiro; Tomioka, Hideki; Morishita, Ryuichi

    2014-10-01

    Therapeutic angiogenesis for the treatment of ischemic disease can be attained through the delivery of recombinant growth factor proteins, through gene transfer or cell transplantation. Gene transfer associated with adenovirus or naked plasmid DNAs has been extensively studied in clinical trials. An investigational product, beperminogene perplasmid, is the naked plasmid DNA encoding the cDNA of human HGF, which has potent angiogenic activity. In several clinical trials, beperminogene perplasmid showed favorable safety and efficacy profile in the treatment of critical limb ischemia. This article reviews the results of pre-clinical and clinical studies of beperminogene perplasmid in the treatment of critical limb ischemia caused by peripheral arterial disease and Buerger's disease. PMID:25190335

  8. Determining End Points for Critical Limb Ischemia Interventions.

    PubMed

    Cooper, Kyle J; Peña, Constantino; Benenati, James

    2016-06-01

    Critical limb ischemia is a condition that has increased in prevalence and carries a high degree of morbidity. Although endovascular therapy for treatment of patients with critical limb ischemia has undergone significant advances with improved outcomes over the past decade, these patients often have multilevel disease, and it may take weeks or months for ulceration healing. For this reason, the acceptable therapeutic end points during and immediately following revascularization remain somewhat obscure. There are multiple tools available to guide the treating vascular specialist in this regard. Establishment of in-line flow to the foot and the angiosome containing the ulceration, appearance of a "wound blush," restoration of pulses, and bleeding at the ulcer site are basic tenets intraprocedurally. Postprocedural noninvasive testing including the ankle-brachial and toe-brachial indices, segmental pressure measurements, pulse volume recordings, transcutaneous oxygen tension, skin perfusion pressures (SPPs), and toe pressures all play a role in determining the likelihood of clinical improvement. Newer technologies such as two-dimensional (2D) perfusion angiography, fluorescence angiography, and tissue oxygen saturation mapping may allow better real-time assessment of flow restoration. In combination with close clinical follow-up and wound care, these tools provide treating physicians with a better grasp of the necessary end points to optimize patients for clinical improvement. PMID:27423992

  9. Cell Therapy in Patients with Critical Limb Ischemia

    PubMed Central

    Compagna, Rita; Amato, Bruno; Massa, Salvatore; Amato, Maurizio; Grande, Raffaele; Butrico, Lucia; de Franciscis, Stefano; Serra, Raffaele

    2015-01-01

    Critical limb ischemia (CLI) represents the most advanced stage of peripheral arterial obstructive disease (PAOD) with a severe obstruction of the arteries which markedly reduces blood flow to the extremities and has progressed to the point of severe rest pain and/or even tissue loss. Recent therapeutic strategies have focused on restoring this balance in favor of tissue survival using exogenous molecular and cellular agents to promote regeneration of the vasculature. These are based on stimulation of angiogenesis by extracellular and cellular components. This review article carries out a systematic analysis of the most recent scientific literature on the application of stem cells in patients with CLI. The results obtained from the detailed analysis of the recent literature data have confirmed the beneficial role of cell therapy in reducing the rate of major amputations in patients with CLI and improving their quality of life. PMID:26300924

  10. Contemporary Treatment for Critical Ischemia: The Evidence for Interventional Radiology or Surgery

    PubMed Central

    Hussey, Keith; Chandramohan, Sivanathan

    2014-01-01

    This article is a review of the evidence regarding the management of patients with critical limb ischemia. The aim of the study is to discuss the definition, incidence, and clinical importance of critical limb ischemia, as well as the aims of treatment in terms of quality of life and limb salvage. Endovascular and surgical treatments should not be viewed as competing therapies. In fact, these are complementary techniques each with strengths and weaknesses. The authors will propose a strategy based on the available evidence for deciding the optimal approach to management of patients with critical limb ischemia. PMID:25435654

  11. Mitochondrial Regulation of the Muscle Microenvironment in Critical Limb Ischemia

    PubMed Central

    Ryan, Terence E.; Schmidt, Cameron A.; Green, Tom D.; Brown, David A.; Neufer, P. Darrell; McClung, Joseph M.

    2015-01-01

    Critical limb ischemia (CLI) is the most severe clinical presentation of peripheral arterial disease and manifests as chronic limb pain at rest and/or tissue necrosis. Current clinical interventions are largely ineffective and therapeutic angiogenesis based trials have shown little efficacy, highlighting the dire need for new ideas and novel therapeutic approaches. Despite a decade of research related to skeletal muscle as a determinant of morbidity and mortality outcomes in CLI, very little progress has been made toward an effective therapy aimed directly at the muscle myopathies of this disease. Within the muscle cell, mitochondria are well positioned to modulate the ischemic cellular response, as they are the principal sites of cellular energy production and the major regulators of cellular redox charge and cell death. In this mini review, we update the crucial importance of skeletal muscle to CLI pathology and examine the evolving influence of muscle and endothelial cell mitochondria in the complex ischemic microenvironment. Finally, we discuss the novelty of muscle mitochondria as a therapeutic target for ischemic pathology in the context of the complex co-morbidities often associated with CLI. PMID:26635622

  12. Critical ischemia time in a model of spinal cord section. A study performed on dogs

    PubMed Central

    Garcia Martinez, David; Rosales Corral, Sergio A.; Flores Soto, Mario E.; Velarde Silva, Gustavo; Portilla de Buen, Eliseo

    2006-01-01

    Vascular changes after acute spinal cord trauma are important factors that predispose quadriplegia, in most cases irreversible. Repair of the spinal blood flow helps the spinal cord recovery. The average time to arrive and perform surgery is 3 h in most cases. It is important to determine the critical ischemia time in order to offer better functional prognosis. A spinal cord section and vascular clamping of the spinal anterior artery at C5–C6 model was used to determine critical ischemia time. The objective was to establish a critical ischemia time in a model of acute spinal cord section. Four groups of dogs were used, anterior approach and vascular clamp of spinal anterior artery with 1, 2, 3, and 4 h of ischemia and posterior hemisection of spinal cord at C5–C6 was performed. Clinical evaluation was made during 12 weeks and morphological evaluation at the end of this period. We obtained a maximal neurological coordination at 23 days average. Two cases showed sequels of right upper limb paresis at 1 and 3 ischemia hours. There was nerve conduction delay of 56% at 3 h of ischemia. Morphological examination showed 25% of damaged area. The VIII and IX Rexed’s laminae were the most affected. The critical ischemia time was 3 h. Dogs with 4 h did not exhibit any recovery. PMID:17024402

  13. Exendin-4 protected against critical limb ischemia in obese mice.

    PubMed

    Sheu, Jiunn-Jye; Chang, Meng-Wei; Wallace, Christopher Glenn; Chiang, Hsin-Ju; Sung, Pei-Hsun; Tsai, Tzu-Hsien; Chung, Sheng-Ying; Chen, Yung-Lung; Chua, Sarah; Chang, Hsueh-Wen; Sun, Cheuk-Kwan; Lee, Fan-Yen; Yip, Hon-Kan

    2015-01-01

    This study tested the hypothesis that exendin-4 protects against critical limb ischemia (CLI) in obese mice undergoing hypoxic stress (H). B6 mice were categorized into aged-matched control (C)-H (group 1-A), obesity (induced by high-fat diet) (O)-H (group 1-B), C-H-CLI (group 2-A), O-H-CLI (group 2-B), C-H-CLI-exendin-4 (group 3-A) and O-H-CLI-exendin-4 (group 3-B). Animals were sacrificed by day 14 after CLI procedure. By day 14, laser Doppler results showed that blood flow in CLI area was higher in group 3-A than group 2-A, higher in group 3-B than group 2-B, highest in groups 1-A and 1-B, higher in group 2-A than in group 2-B, and higher in group 3-A than in group 3-B (all p<0.001), but not significantly different between groups 1-A and 1-B. Furthermore, circulating numbers of endothelial progenitor cells (EPCs) (c-kit/CD31+, Sca-1/KDR+) showed an identical pattern of blood flow in CLI area among groups 2-A, 2-B, 3-A and 3-B, except that these biomarkers were lowest in groups 1-A and 1-B (all p<0.001). Protein and cellular levels of angiogenesis factors (VEGF, CXCR4, SDF-1α) exhibited an identical pattern of circulating EPC numbers among all groups (all p<0.001). Protein levels of apoptotic (cytosolic cytochrome-C, mitochondrial Bax, cleaved caspase 3 and PARP) and fibrotic (Samd 3, TGF-β) biomarkers showed an opposite pattern of blood flow in CLI area among groups 2-A, 2-B, 3-A and 3-B, but were lowest in groups 1-A and 1-B (all p<0.001). This finding suggests exendin-4 protected against CLI in obese mice undergoing hypoxic stress mainly through enhancing angiogenesis and inhibiting apoptosis. PMID:26045886

  14. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    SciTech Connect

    Madaric, Juraj; Klepanec, Andrej; Mistrik, Martin; Altaner, Cestmir; Vulev, Ivan

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  15. Systematic investigation of transcription factors critical in the protection against cerebral ischemia by Danhong injection.

    PubMed

    Wei, Junying; Zhang, Yanqiong; Jia, Qiang; Liu, Mingwei; Li, Defeng; Zhang, Yi; Song, Lei; Hu, Yanzhen; Xian, Minghua; Yang, Hongjun; Ding, Chen; Huang, Luqi

    2016-01-01

    Systematic investigations of complex pathological cascades during ischemic brain injury help to elucidate novel therapeutic targets against cerebral ischemia. Although some transcription factors (TFs) involved in cerebral ischemia, systematic surveys of their changes during ischemic brain injury have not been reported. Moreover, some multi-target agents effectively protected against ischemic stroke, but their mechanisms, especially the targets of TFs, are still unclear. Therefore, a comprehensive approach by integrating network pharmacology strategy and a new concatenated tandem array of consensus transcription factor response elements method to systematically investigate the target TFs critical in the protection against cerebral ischemia by a medication was first reported, and then applied to a multi-target drug, Danhong injection (DHI). High-throughput nature and depth of coverage, as well as high quantitative accuracy of the developed approach, make it more suitable for analyzing such multi-target agents. Results indicated that pre-B-cell leukemia transcription factor 1 and cyclic AMP-dependent transcription factor 1, along with six other TFs, are putative target TFs for DHI-mediated protection against cerebral ischemia. This study provides, for the first time, a systematic investigation of the target TFs critical to DHI-mediated protection against cerebral ischemia, as well as reveals more potential therapeutic targets for ischemic stroke. PMID:27431009

  16. Systematic investigation of transcription factors critical in the protection against cerebral ischemia by Danhong injection

    PubMed Central

    Wei, Junying; Zhang, Yanqiong; Jia, Qiang; Liu, Mingwei; Li, Defeng; Zhang, Yi; Song, Lei; Hu, Yanzhen; Xian, Minghua; Yang, Hongjun; Ding, Chen; Huang, Luqi

    2016-01-01

    Systematic investigations of complex pathological cascades during ischemic brain injury help to elucidate novel therapeutic targets against cerebral ischemia. Although some transcription factors (TFs) involved in cerebral ischemia, systematic surveys of their changes during ischemic brain injury have not been reported. Moreover, some multi-target agents effectively protected against ischemic stroke, but their mechanisms, especially the targets of TFs, are still unclear. Therefore, a comprehensive approach by integrating network pharmacology strategy and a new concatenated tandem array of consensus transcription factor response elements method to systematically investigate the target TFs critical in the protection against cerebral ischemia by a medication was first reported, and then applied to a multi-target drug, Danhong injection (DHI). High-throughput nature and depth of coverage, as well as high quantitative accuracy of the developed approach, make it more suitable for analyzing such multi-target agents. Results indicated that pre-B-cell leukemia transcription factor 1 and cyclic AMP-dependent transcription factor 1, along with six other TFs, are putative target TFs for DHI-mediated protection against cerebral ischemia. This study provides, for the first time, a systematic investigation of the target TFs critical to DHI-mediated protection against cerebral ischemia, as well as reveals more potential therapeutic targets for ischemic stroke. PMID:27431009

  17. New aspects of delirium in elderly patients with critical limb ischemia

    PubMed Central

    van Eijsden, Willem A; Raats, Jelle W; Mulder, Paul GH; van der Laan, Lijckle

    2015-01-01

    Objective The primary objective was to identify possible risk factors for delirium in patients with critical limb ischemia undergoing surgery. The secondary objective was to study the effect of delirium on complications, the length of hospital stay, health care costs, and mortality. Methods All patients 65 years or older with critical limb ischemia undergoing surgery from February 2013 to July 2014 at Amphia Hospital, were included and followed up until December 31, 2014. Delirium was scored using the Delirium Observation Screening Scale (DOSS). Perioperative risk factors (age, comorbidity, factors of frailty, operation type, hemoglobulin, and transfusion) were collected and analyzed using logistic regression. Secondary outcomes were the number of complications, total hospital stay, extra health care costs per delirium, and mortality within 3 months and 6 months of surgery. Results We included 92 patients with critical limb ischemia undergoing surgery. Twenty-nine (32%) patients developed a delirium during admission, of whom 17 (59%) developed delirium preoperatively. After multivariable analysis, only diabetes mellitus (odds ratio [OR] =6.23; 95% confidence interval [CI]: 1.11–52.2; P=0.035) and Short Nutritional Assessment Questionnaire for Residential Care (SNAQ-RC) ≥3 (OR =5.55; 95% CI: 1.07–42.0; P=0.039) was significantly associated with the onset of delirium. Delirium was associated with longer hospital stay (P=0.001), increased health care costs, and higher mortality after 6 months (P<0.001). Conclusion Delirium is a common adverse event in patients with critical limb ischemia undergoing surgery with devastating outcome in the long term. Most patients developed delirium preoperatively, which indicates the need for early recognition and preventive strategies in the preoperative period. This study identified undernourishment and diabetes mellitus as independent risk factors for delirium. PMID:26451094

  18. Crural Bypass for Critical Lower Limb Ischemia with Omniflow II Prosthesis.

    PubMed

    Dünschede, Friedrich; Stabrauskaite, Justina; Weisser, Gerhard; Espinola-Klein, Christine; Dorweiler, Bernhard; Vahl, Christian-Friedrich

    2016-06-01

    Background Reports about the use of the Omniflow II prosthesis (Bio Nova International, Victoria, Australia) in a crural position in patients with critical lower limb ischemia are rare. Methods All crural bypass operations were registered in a database. Primary end points of the study were amputation-free survival, limb salvage, and long-term patency. Results From January 2007 to December 2012, we implanted 27 Omniflow II prostheses in the crural position for critical lower limb ischemia. Of these, 12 crural bypasses were conducted with adjuvant distal arteriovenous fistula as a means to increase bypass flow in the presence of severely impaired intraoperative runoff or revision for early failure. Fifteen Omniflow II prosthesis bypasses were performed in the crural position without fistula. Overall, two patients died postoperatively. The limb salvage rate was 92% in the fistula group compared with 60% in the nonfistula group after a median observation time of 19 months in patients getting Omniflow prosthesis bypasses. Conclusion Omniflow II prosthesis in patients with critical lower limb ischemia and absence of sufficient autologous vein is durable. Moreover, the use of adjuvant distal arteriovenous fistula may increase the chance of limb salvage in this group of patients. PMID:26291743

  19. Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia

    PubMed Central

    2012-01-01

    The therapeutic potential of mesenchymal stem cell (MSC) transplantation for the treatment of ischemic conditions such as coronary artery disease, peripheral arterial disease, and stroke has been explored in animal models and early-phase clinical trials. A substantial database documents the safety profile of MSC administration to humans in a large number of disease states. The mechanism of the therapeutic effect of MSC transplantation in ischemic disease has been postulated to be due to paracrine, immunomodulatory, and differentiation effects. This review provides an overview of the potential role of MSC-based therapy for critical limb ischemia (CLI), the comparison of MSC cellular therapy with angiogenesis gene therapy in CLI, and the proposed mechanism of action of MSC therapy. Preclinical efficacy data in animal models of hindlimb ischemia, current early-phase human trial data, and considerations for future MSC-based therapy in CLI will also be discussed. PMID:22846185

  20. The role of hybrid procedures in the treatment of critical limb ischemia.

    PubMed

    Setacci, C; Galzerano, G; Sirignano, P; Mazzitelli, G; Sauro, L; de Donato, G; Benevento, D; Cappelli, A; Setacci, F

    2013-12-01

    Patients affected by critical limb ischemia (CLI) represent a complex and high risk clinical problem, and a multidisciplinary approach is often demanded. The amputation rate in patients affected by CLI is still high. Introduction of endovascular procedure shook up the CLI concept of treatment. The increasing experience of Vascular Surgeons in endovascular technique forced these specialist to match classic surgical skills and endovascular tools in order to achieve the best treatment for each patients. The combination of the two techniques identifies the hybrid procedure. Aim of this paper is to define indication, necessity and results of the hybrid procedure in patients suffering from CLI. PMID:24126510

  1. Spinal Cord Stimulation Therapy for the Treatment of Concomitant Phantom Limb Pain and Critical Limb Ischemia.

    PubMed

    De Caridi, Giovanni; Massara, Mafalda; Serra, Raffaele; Risitano, Claudia; Giardina, Massimiliano; Acri, Ignazio Eduardo; Volpe, Pietro; David, Antonio

    2016-04-01

    Phantom limb pain (PLP) is a chronic condition experienced by about 80% of patients who have undergone amputation. In most patients, both the frequency and the intensity of pain attacks diminish with time, but severe pain persists in about 5-10%. Probably, factors in both the peripheral and central nervous system play a role in the occurrence and persistence of pain in the amputated lower limb. The classical treatment of PLP can be divided into pharmacologic, surgical, anesthetic, and psychological modalities. Spinal cord stimulation (SCS) does not represent a new method of treatment for this condition. However, the concomitant treatment of PLP and critical lower limb ischemia by using SCS therapy has not yet been described in the current literature. The aim of the present article is to highlight the possibility of apply SCS for the simultaneous treatment of PLP and critical lower limb ischemia on the contralateral lower limb after failure of medical therapy in a group of 3 patients, obtaining pain relief in both lower limbs, delaying an endovascular or surgical revascularization. After SCS implantation and test stimulation, the pain was reduced by 50% on both the right and the left side in all our patients. The main indications for permanent SCS therapy after 1 week of test stimulation were represented by transcutaneous oxygen (TcPO2) increase >75%, decrease of opioids analgesics use of at least 50% and a pain maintained to within 20-30/100 mm on visual analog scale. PMID:26802307

  2. Preclinical evaluation of mesenchymal stem cells overexpressing VEGF to treat critical limb ischemia.

    PubMed

    Beegle, Julie R; Magner, Nataly Lessa; Kalomoiris, Stefanos; Harding, Aja; Zhou, Ping; Nacey, Catherine; White, Jeannine Logan; Pepper, Karen; Gruenloh, William; Annett, Geralyn; Nolta, Jan A; Fierro, Fernando A

    2016-01-01

    Numerous clinical trials are utilizing mesenchymal stem cells (MSC) to treat critical limb ischemia, primarily for their ability to secrete signals that promote revascularization. These cells have demonstrated clinical safety, but their efficacy has been limited, possibly because these paracrine signals are secreted at subtherapeutic levels. In these studies the combination of cell and gene therapy was evaluated by engineering MSC with a lentivirus to overexpress vascular endothelial growth factor (VEGF). To achieve clinical compliance, the number of viral insertions was limited to 1-2 copies/cell and a constitutive promoter with demonstrated clinical safety was used. MSC/VEGF showed statistically significant increases in blood flow restoration as compared with sham controls, and more consistent improvements as compared with nontransduced MSC. Safety of MSC/VEGF was assessed in terms of genomic stability, rule-out tumorigenicity, and absence of edema or hemangiomas in vivo. In terms of retention, injected MSC/VEGF showed a steady decline over time, with a very small fraction of MSC/VEGF remaining for up to 4.5 months. Additional safety studies completed include absence of replication competent lentivirus, sterility tests, and absence of VSV-G viral envelope coding plasmid. These preclinical studies are directed toward a planned phase 1 clinical trial to treat critical limb ischemia. PMID:27610394

  3. Preclinical evaluation of mesenchymal stem cells overexpressing VEGF to treat critical limb ischemia

    PubMed Central

    Beegle, Julie R; Magner, Nataly Lessa; Kalomoiris, Stefanos; Harding, Aja; Zhou, Ping; Nacey, Catherine; White, Jeannine Logan; Pepper, Karen; Gruenloh, William; Annett, Geralyn; Nolta, Jan A; Fierro, Fernando A

    2016-01-01

    Numerous clinical trials are utilizing mesenchymal stem cells (MSC) to treat critical limb ischemia, primarily for their ability to secrete signals that promote revascularization. These cells have demonstrated clinical safety, but their efficacy has been limited, possibly because these paracrine signals are secreted at subtherapeutic levels. In these studies the combination of cell and gene therapy was evaluated by engineering MSC with a lentivirus to overexpress vascular endothelial growth factor (VEGF). To achieve clinical compliance, the number of viral insertions was limited to 1–2 copies/cell and a constitutive promoter with demonstrated clinical safety was used. MSC/VEGF showed statistically significant increases in blood flow restoration as compared with sham controls, and more consistent improvements as compared with nontransduced MSC. Safety of MSC/VEGF was assessed in terms of genomic stability, rule-out tumorigenicity, and absence of edema or hemangiomas in vivo. In terms of retention, injected MSC/VEGF showed a steady decline over time, with a very small fraction of MSC/VEGF remaining for up to 4.5 months. Additional safety studies completed include absence of replication competent lentivirus, sterility tests, and absence of VSV-G viral envelope coding plasmid. These preclinical studies are directed toward a planned phase 1 clinical trial to treat critical limb ischemia. PMID:27610394

  4. The expression profile of angiogenic genes in critical limb ischemia popliteal arteries.

    PubMed

    Baczynska, D; Michalowska, D; Barc, P; Skora, J; Karczewski, M; Sadakierska-Chudy, A

    2016-06-01

    Critical limb ischemia (CLI) represents the most severe form of peripheral arterial disease (PAD) and is the leading cause of non-traumatic amputations in western populations. In recent years, therapeutic angiogenesis has been considered to be a potential treatment option for CLI patients, however the molecular mechanism of ischemia-induced vascularization is still not fully understood. The identification of genetic factors underlying vascular responses to ischemia will improve our understanding of the biological causes of the disease and enhance personalized therapies in the future. In this work, we determined, for the first time, the expression profile of angiogenesis-related genes utilizing unique human material: the popliteal arteries retrieved during lower limb amputation from patients with CLI. Using custom-designed TaqMan Low-Density Array (TLDA) cards we investigated the mRNA level of 90 genes on CLI samples compared to healthy donors. We identified three significantly up-regulated genes in CLI group: matrix metalloproteinase 9 (MMP-9), VE-cadherin (CDH5) and integrin alpha 4 (ITGA4). However, among all investigated genes, only lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) was significantly reduced. In order to verify whether hypoxic conditions occur in popliteal arteries of CLI patients, we validated the transcription level of selected proangiogenic genes by real-time PCR on a larger number of samples. These results showed that the expression of key genes involved in angiogenesis, such as MMP9, HGF, HIF1A, VEGF-A and FLT1 were elevated in patients with CLI. Moreover, the study revealed that the expression of VEGF-A and FLT1 was associated with activation of HIF1A transcription. In conclusion, our data revealed the alteration in the mRNA level of genes involved in matrix remodelling, cell-cell adhesion as well as endothelial cell migration and proliferation in human popliteal arteries. PMID:27511996

  5. Neovascularization Capacity of Mesenchymal Stromal Cells From Critical Limb Ischemia Patients Is Equivalent to Healthy Controls

    PubMed Central

    Gremmels, Hendrik; Teraa, Martin; Quax, Paul HA; den Ouden, Krista; Fledderus, Joost O; Verhaar, Marianne C

    2014-01-01

    Critical limb ischemia (CLI) is often poorly treatable by conventional management and alternatives such as autologous cell therapy are increasingly investigated. Whereas previous studies showed a substantial impairment of neovascularization capacity in primary bone-marrow (BM) isolates from patients, little is known about dysfunction in patient-derived BM mesenchymal stromal cells (MSCs). In this study, we have compared CLI-MSCs to healthy controls using gene expression profiling and functional assays for differentiation, senescence and in vitro and in vivo pro-angiogenic ability. Whereas no differentially expressed genes were found and adipogenic and osteogenic differentiation did not significantly differ between groups, chondrogenic differentiation was impaired in CLI-MSCs, potentially as a consequence of increased senescence. Migration experiments showed no differences in growth factor sensitivity and secretion between CLI- and control MSCs. In a murine hind-limb ischemia model, recovery of perfusion was enhanced in MSC-treated mice compared to vehicle controls (71 ± 24% versus 44 ± 11%; P < 1 × 10−6). CLI-MSC- and control-MSC–treated animals showed nearly identical amounts of reperfusion (ratio CLI:Control = 0.98, 95% CI = 0.82–1.14), meeting our criteria for statistical equivalence. The neovascularization capacity of MSCs derived from CLI-patients is not compromised and equivalent to that of control MSCs, suggesting that autologous MSCs are suitable for cell therapy in CLI patients. PMID:25174586

  6. Hybrid treatment of lower limb critical ischemia in a patient with systemic lupus erythematosus.

    PubMed

    Giannakakis, Sotirios; Galyfos, George; Stefanidis, Ioannis; Kastrisios, Georgios; Maltezos, Chrisostomos

    2015-04-01

    Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystemic disease, which affects primarily small-sized vessels, arterioles, venules, and capillaries in the cardiovascular system. Less often, medium-sized vessels are affected, and large-sized vessels are affected rarely. We report an unusual case of a 52-year-old female patient with SLE under treatment and multileveled arterial obstructive disease of the lower limb, who presented with critical limb ischemia. The patient was treated using a hybrid endovascular and open revascularization procedure, on the basis of the clinical picture of the patient, the angiographic findings, and the experience of our department. Our aim is not only to highlight the rarity of the clinical picture but also to make useful conclusions regarding the proper management for such unusual cases. Given the fact that there are no guidelines, we present the treatment strategy selected for our patient and discuss our results. PMID:25596409

  7. Using the diamond intermediate anastomosis in composite sequential bypass grafting for critical limb ischemia.

    PubMed

    Rogers, Ailín C; Reddy, Paul W; Cross, K Simon; McMonagle, Morgan P

    2016-04-01

    Composite sequential bypass grafting is an effective alternative in the treatment of peripheral vascular disease when autologous vein is limited. We describe a modified technique for composite sequential bypass grafting anastomosis using a combination of synthetic graft with native vein connected via a common intermediate anastomotic junction, which also benefits from having additional outflow at the native, noncontiguous arteriotomy in a diamond configuration. This technique was piloted on six patients to treat critical limb ischemia when no other revascularization options were deemed suitable. Limb salvage with resolution of symptoms was achieved in all six patients at the 6-month follow-up. The diamond anastomosis is a promising method to maximize limb salvage using a unique composite sequential bypass configuration when native vein is limited. PMID:27016861

  8. Simultaneous versus two-stage multisegmental reconstruction for critical lower limb ischemia.

    PubMed

    Zukauskas, G; Ulevicius, H

    1995-07-01

    Treatment of critical limb ischemia (CLI) remains one of the most demanding problems of vascular surgery, especially when it is due to multisegmental occlusive arterial disease. Three main options of treatment are accepted: inflow procedure alone, simultaneous inflow and outflow reconstructions, or two-stage surgery. To compare the results of the latter two was the aim of this study. During a six year period from 1987 to 1992, 1953 aortofemoral reconstructions were performed. In 245 cases (12.5%), sequential aortofemorodistal (popliteal or tibial) procedures were necessary for successful treatment of CLI - Grade III and IV Fountain. In 161 cases, two-segment reconstruction was performed in one stage (Group A), and in 84 cases (Group B), two separate operations were done - outflow procedure followed after the inflow surgery. Results in perioperative and remote postoperative periods were analyzed regarding limb salvage and graft patency rates using a life table method. Perioperative mortality was 3% in Group A and 6% in Group B. The limb salvage rate was 95.6% at one year and 90.4% at five(A), and 88.8% and 80% (B) respectively. Primary overall graft patency rate was 91.4% at one year and 65.5% at five (A) and 84.9% and 59.4% (B) respectively. Secondary graft patency was 92.2% at one year and 81.8% at five (A) and 86.1% and 65.9% (B). Analysis of the data demonstrates that simultaneous multisegmental reconstructions for critical limb ischemia are a safe and effective method of treatment and superior when compared with two-stage surgery. PMID:17590601

  9. Critical finger ischemia and myocardial fibrosis development after sudden interruption of sildenafil treatment in a systemic sclerosis patient.

    PubMed

    Bruni, C; Bellando-Randone, S; Gargani, L; Picano, E; Pingitore, A; Matucci-Cerinic, M; Guiducci, S

    2016-01-01

    Systemic sclerosis (SSc) is a connective tissue disease frequently associated with Raynaud's Phenomenon (RP). Among possible pharmacological treatments, phosphodiesterase 5 inhibitors are considered in cases of severe non -responsive RP. We present the case of a male SSc patient wh presented with critical finger ischemia and concomitant appearance of myocardial fibrosis after sudden interruption of sildenafil treatment. PMID:27608801

  10. Autologous transplantation of CD34(+) bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia.

    PubMed

    Ismail, Ahmed M; Abdou, Said M; Aty, Hassan Abdel; Kamhawy, Adel H; Elhinedy, Mohammed; Elwageh, Mohammed; Taha, Atef; Ezzat, Amal; Salem, Hoda A; Youssif, Said; Salem, Mohamed L

    2016-08-01

    Patients with a decrease in limb perfusion with a potential threat to limb viability manifested by ischemic rest pain, ischemic ulcers, and/or gangrene are considered to have critical limb ischemia (CLI). Because of this generally poor outcome, there is a strong need for attempting any procedure to save the affected limb. The aim of this work is to evaluate the possibility to use stem cell therapy as a treatment option for patients with chronic critical lower limb ischemia with no distal run off. This study includes 20 patients with chronic critical lower limb ischemia with no distal run off who are unsuitable for vascular or endovascular option. These patients underwent stem cell therapy (SCT) by autologous transplantation of bone marrow derived mononuclear cells. 55 % of patients treated with SCT showed improvement of the rest pain after the first month, 60 % continued improvement of the rest pain after 6 months, 75 % after 1 year and 80 % after 2 years and continued without any deterioration till the third year. Limb salvage rate after STC was 80 % after the first year till the end of the second and third years. SCT can result in angiogenesis in patients with no-option CLI, providing a foundation for the application of this therapy to leg ischemia. PMID:25511801

  11. Gastrointestinal ischemia monitoring through impedance spectroscopy as a tool for the management of the critically ill.

    PubMed

    Beltran, Nohra E; Sacristan, Emilio

    2015-07-01

    Impedance spectroscopy (IS) has been proposed as a tool for monitoring mucosal tissue ischemia and damage in the gut of critically ill patients resulting from shock and hypoperfusion. A specific device and system have been developed and tested for this specific application over the past 12 years by our research group. This paper reviews previously published studies as well as unpublished experimental results, and puts the whole in context and perspective to help understand this technology. Results presented include summaries of gastric reactance measurement understanding, in vivo measurements in animal models, clinical significance of the measurement, and future perspectives of clinical use of this technology. All of the experimental work done to date has been designed to determine the evolving device prototypes' performance and limitations from an instrumentation point of view. Although there are still questions to be answered with regard to the IS measurement, we conclude that we have reached enough confidence in the measurement and the device's performance and safety to begin clinically oriented research to learn how this technology may be useful in the diagnosis and management of different populations of the critically ill. PMID:25711880

  12. Always Contact a Vascular Interventional Specialist Before Amputating a Patient with Critical Limb Ischemia

    SciTech Connect

    Met, Rosemarie; Koelemay, Mark J. W.; Bipat, Shandra; Legemate, Dink A.; Lienden, Krijn P. van; Reekers, Jim A.

    2010-06-15

    Patients with severe critical limb ischemia (CLI) due to long tibial artery occlusions are often poor candidates for surgical revascularization and frequently end up with a lower limb amputation. Subintimal angioplasty (SA) offers a minimally invasive alternative for limb salvage in this severely compromised patient population. The objective of this study was to evaluate the results of SA in patients with CLI caused by long tibial occlusions who have no surgical options for revascularization and are facing amputation. We retrospectively reviewed all consecutive patients with CLI due to long tibial occlusions who were scheduled for amputation because they had no surgical options for revascularization and who were treated by SA. A total of 26 procedures in 25 patients (14 males; mean age, 70 {+-} 15 [SD] years) were evaluated. Technical success rate was 88% (23/26). There were four complications, which were treated conservatively. Finally, in 10 of 26 limbs, no amputation was needed. A major amputation was needed in 10 limbs (7 below-knee amputations and 3 above-knee amputations). Half of the major amputations took place within 3 months after the procedure. Cumulative freedom of major amputation after 12 months was 59% (SE = 11%). In six limbs, amputation was limited to a minor amputation. Seven patients (28%) died during follow-up. In conclusion, SA of the tibial arteries seem to be a valuable treatment option to prevent major amputation in patients with CLI who are facing amputation due to lack of surgical options.

  13. Perfusion Angiography of the Foot in Patients with Critical Limb Ischemia: Description of the Technique

    SciTech Connect

    Jens, Sjoerd Marquering, Henk A.; Koelemay, Mark J. W.; Reekers, Jim A.

    2015-02-15

    ObjectiveTo study the feasibility of 2D perfusion imaging in critical limb ischemia (CLI).Methods/ResultsPerfusion angiography is a new technology which was tested in 18 patients with CLI of the foot. A standardized protocol was used with a catheter placed at the mid-part of the popliteal artery, and a total of 9 cc of non-ionic iodinated contrast material was injected at a rate of 3 cc/sec. The technology is based on early cardiology research where iodinated contrast agents were used for imaging of cardiac perfusion. During the first pass of the contrast, there is a significant diffusion of the contrast agents into the interstitial space, particularly for non-ionic and low-molecular-weight compounds.DiscussionThe original angiography data can be used to make a time–density curve, which represents the actual perfusion of the foot in time. Angiographic perfusion imaging is a post-processing modality for which no extra contrast or radiation is needed. With this technique, it is possible to get more information about the perfusion status and microcirculation of the foot. This is a step toward functional imaging in CLI patients.

  14. Spinal cord stimulation for patients with inoperable chronic critical leg ischemia

    PubMed Central

    Chen, Xiao-pei; Fu, Wei-min; Gu, Wei

    2011-01-01

    BACKGROUND: Because of the prevalence of diabetes, the treatment of diabetic foot is still challenging. Even an exactly proved effective and practical method can’t be listed except vascular surgery which is not a long-term way for it. Spinal cord stimulation (SCS) is a very promising option in the treatment algorithm of inoperable chronic critical leg ischemia (CLI). DATA SOURCES: We searched Pubmed database with key words or terms such as “spinal cord stimulation”, “ischemic pain” and “limb ischemia” appeared in the last five years. RESULTS: The mechanism of SCS is unclear. Two theories have emerged to interpret the benefits of SCS. Pain relief from SCS can be confirmed by a majority of the studies, while limb salvage and other more ambitious improvements have not come to an agreement. The complications of SCS are not fatal, but most of them are lead migration, lead connection failure, and local infection. CONCLUSIONS: SCS is a safe, promising treatment for patients with inoperable CLI. It is effective in pain reduction compared with traditional medical treatment. PMID:25215020

  15. Endovascular first as "preliminary approach" for critical limb ischemia and diabetic foot.

    PubMed

    Setacci, C; Sirignano, P; Galzerano, G; Mazzitelli, G; Sauro, L; de Donato, G; Benevento, D; Cappelli, A; Setacci, F

    2013-12-01

    The treatment of the critical limb ischemia (CLI) and diabetic foot (DB) is still object of discussion and the gold standard for revascularization has not yet been identified. In these two decades the introduction of endovascular procedures had a large impact on the surgical revascularization and were added to the practice of vascular surgeons in patients who cannot be candidates for a bypass. This may be due to significant comorbidities, a reduced life expectancy, infection or gangrene in the possible sites of distal anastomoses, the unavailability of suitable veins, or the absence of an adequate "landing zone" for the distal part of the bypass. Various studies have evaluated the role of PTA in DF and CLI that resulted favourable in terms of feasibility, technical efficacy, the reduced number of complications, and limb salvage rates. Anyway, long-term patency is better after bypass surgery than after angioplasty, which is burdened by a high restenosis rate. In our experience we tried to practice endovascular approach as a first choice. If the procedure cannot be concluded safely, we continue the intervention surgically or use a hybrid approach. The endovascular-first strategy seems to be the future regardless of comorbidity of the patient and the degree of pathology. The vascular surgeon remains the only specialist that can decide the correct intervention without pressure or been forced and, last but not least, the only one who can independently perform hybrid interventions. PMID:24126506

  16. Baseline Platelet Activation and Reactivity in Patients with Critical Limb Ischemia

    PubMed Central

    de Borst, Gert Jan; Verhaar, Marianne C.; Roest, Mark; Moll, Frans L.

    2015-01-01

    Background Patients with critical limb ischemia (CLI) have a high risk to develop cardiovascular events (CVE). We hypothesized that in CLI patients platelets would display increased baseline activation and reactivity. Objectives We investigated baseline platelet activation and platelet reactivity in patients with CLI. Patients/Methods In this study baseline platelet activation and platelet reactivity in response to stimulation of all major platelet activation pathways were determined in 20 CLI patients (11 using aspirin and 9 using vitamin K-antagonists) included in the Juventas-trial (clinicaltrials.gov NCT00371371) and in 17 healthy controls. Platelet activation was quantified with flow cytometric measurement of platelet P-selectin expression and fibrinogen binding. Results CLI patients not using aspirin showed higher baseline platelet activation compared to healthy controls. Maximal reactivity to stimulation of the collagen and thrombin activation pathway was decreased in CLI patients compared to healthy controls. In line, attenuated platelet reactivity to stimulation of multiple activation pathways was associated with several traditional risk factors for cardiovascular disease. Conclusions Baseline platelet activation was increased in CLI patients, whereas the reactivity of circulating platelets to several stimulatory agents is decreased. Reactivity of platelets was inversely correlated with cardiovascular risk factors. PMID:26148006

  17. Clinical Outcomes of Infrapopliteal Angioplasty in Patients With Critical Limb Ischemia

    PubMed Central

    Ryu, Hyeon Min; Kim, Jung-Sun; Ko, Young Guk; Hong, Myeong-Ki; Jang, Yangsoo

    2012-01-01

    Background and Objectives With recent advances in equipment and techniques, infrapopliteal angioplasty has shown results that are comparable to those of surgical bypass in patients with critical limb ischemia (CLI). In this study, we evaluated the efficacy and the feasibility of infrapopliteal angioplasty in patients with CLI. Subjects and Methods Between March 2002 and May 2008, infrapopliteal angioplasty was performed on 118 limbs of 101 patients (79 males; mean age 66 years) with CLI (Rutherford category 4, 5 or 6). Freedom from reintervention, limb salvage, and overall survival were analyzed. Results The median follow-up duration was 30 months. Initial technical and clinical success rates were 69.5% and 83.1%, respectively. No major complication requiring surgical intervention developed after angioplasty. Among 82 limbs with initial technical success, the rate of freedom from any reintervention at 2 years was 70.7% and that from limb salvage was 97.6%. Young age and Rutherford category 6 at initial presentation were independent predictors associated with poor 2 year primary patency in these patients with CLI. Overall survival at 1 year was 86.4% and that at 2 years 76.3%. A history of cerebrovascular accident was an independent predictor associated with poor 2 year survival in these patients. Conclusion Infrapopliteal angioplasty as a primary choice of treatment in CLI patients showed favorable clinical outcomes and feasibility. PMID:22563339

  18. Effects of transvenous regional guanethidine block in the treatment of critical finger ischemia.

    PubMed

    Stümpflen, A; Ahmadi, A; Attender, M; Gschwandtner, M; Hofmann, S; Maca, T; Schnürer, G; Minar, E

    2000-02-01

    The objective of this study was to determine the effects of transvenous regional guanethidine block in the treatment of patients with critical finger ischemia. Twenty-seven patients (17 collagen vascular disease, four thromboangiitis obliterans, three embolism, three atherothrombosis) presenting with ischemic rest pain and/or ulcerations of the fingers received a single block with 5 mg guanethidine injected in 60 mL into the clinically more affected hand under 30 minutes of arterial arrest. Marked hyperemia was induced in the treated upper limb, increases (p < 0.01) in finger blood flow, finger skin temperature, and laser Doppler flux were higher and longer lasting than in forearm blood flow, persisting for a whole month. Effects in patients with ischemic finger ulcers were less pronounced than in those without, yet statistically significant increases of all evaluated parameters were observed in these patients too. No effects were seen in the contralateral untreated upper limb or in systemic blood pressure. Subjective symptoms (reduction of rest pain, numbness, vasospastic attacks) were improved in 25/27 (92.6%) patients, ischemic rest pain disappeared in 20/27 (74.1%), and complete healing of finger tip ulcerations within 1 month was achieved in 10/12 (83.3%) affected patients. No side effects were observed. This described method combines good clinical efficacy with lack of undesirable side effects and can be repeated easily. Therefore, this technique is recommended for broader clinical use. PMID:10701719

  19. The need for improved risk stratification in chronic critical limb ischemia.

    PubMed

    Chung, Jayer; Modrall, J Gregory; Valentine, R James

    2014-12-01

    Vascular surgeons are well acquainted with chronic critical limb ischemia (CLI), the most severe manifestation of peripheral arterial disease, with patients presenting with ischemic rest pain or ulcerations, or both. Epidemiologic data predict a burgeoning epidemic of CLI within the United States, commensurate with the increasing incidence and prevalence of atherosclerotic risk factors, especially age and diabetes. Untreated, the risk of major amputation (above the ankle) or death, or both, ranges between 20% and 40% at 1 year. Current open and endovascular therapies have imperfect results, diverse treatment options, and recommendations that are often conflicting and confuse physicians, industry, and patients alike. The best treatment options are ideally evaluated by prospective, randomized controlled trials. However, these have proven impractical in CLI because the rapid evolution of devices and techniques has outstripped the ability to measure outcomes and compare treatment options. Alternatively, risk-stratifying models have been proposed to allow physicians, patients, and industry to objectively evaluate new therapeutics and devices as they evolve. These models are developed from prospective cohorts to identify and quantify variables that can subsequently predict outcome in individual patients. The risk stratification models can also compare CLI outcomes between physicians and institutions, supporting quality assessments, and compensation decisions within Accountable Care Organizations under the Affordable Health Care Act (ACA). Widespread adoption of risk-stratification schemes has yet to occur, despite the critical need for such a tool in CLI, because present models lack optimal predictive ability and generalizability. The passage of the ACA amplifies the importance of developing an improved risk-stratification tool to ensure equitable quality assessments and compensation. This review presents current risk-stratification models for CLI with a summary of the

  20. Effects of electrical stimulation therapy on the blood flow in chronic critical limb ischemia patients following regenerative therapy

    PubMed Central

    Yamabata, Shiho; Shiraishi, Hirokazu; Munechika, Mai; Fukushima, Hideki; Fukuoka, Yoshiyuki; Hojo, Tatsuya; Shirayama, Takeshi; Horii, Motoyuki; Matoba, Satoaki; Kubo, Toshikazu

    2016-01-01

    Objectives: We investigated the effects of electrical stimulation therapy on cutaneous and muscle blood flow in critical limb ischemia patients following regenerative therapy. Methods: Three groups were studied: 10 healthy young subjects, 10 elderly subjects, and 7 critical limb ischemia patients after regenerative therapy. After 5 min rest, electrical stimulation was applied at 5 Hz on the tibialis anterior muscle for 10 min. We estimated the relative changes in oxyhemoglobin and total hemoglobin compared to the basal values at rest (Δ[HbO2], Δ[Hbtot]), which reflected the blood flow in the skin and muscle layer, and we simultaneously measured the tissue O2 saturation (StO2) throughout the electrical stimulation and recovery phase by near-infrared spectroscopy. Results: The Δ[HbO2] and Δ[Hbtot] values of the muscle layer in critical limb ischemia patients increased gradually and remained significantly higher at the 5-min and 10-min recovery periods after the electrical stimulation without reducing the StO2, but there is no significant change in the other two groups. Skin blood flow was not influenced by electrical stimulation in three groups. Conclusion: This improvement of the peripheral circulation by electrical stimulation would be beneficial as the adjunctive therapy after regenerative cell therapy. PMID:27504185

  1. Cell therapy in critical limb ischemia: current developments and future progress.

    PubMed

    Mamidi, Murali Krishna; Pal, Rajarshi; Dey, Sovan; Bin Abdullah, Basri Johan Jeet; Zakaria, Zubaidah; Rao, Mahendra S; Das, Anjan Kumar

    2012-09-01

    Critical limb ischemia (CLI) is a syndrome manifested by ischemic rest pain, non-healing ulcers and tissue loss. CLI patients are at very high risk of amputation and experience poor physical function, leading to severe morbidity and mortality. The fundamental goal for CLI treatment is to relieve ischemic rest pain, heal ulcers, prevent limb loss and improve the quality of life, thereby extending the survival of the patient. Surgical or endovascular revascularization aimed at increasing blood flow is currently available for limb salvage in CLI. However, up to 30% of CLI patients are not suitable for such interventions because of high operative risk or unfavorable vascular anatomy. Therefore exploring new and more effective strategies for revascularization of ischemic limbs is imperative for the establishment of a viable therapeutic alternative. With the emergence of new approaches, this review describes up-to-date progress and developments in cell-based therapy as a novel and promising alternative for CLI treatment. Preliminary clinical data have established the safety, feasibility and efficacy of stem cells, and numerous studies are underway to consolidate this evidence further. However, significant hurdles remain to be addressed before this research can be responsibly translated to the bedside. In particular, we need better understanding of the behavior of cells post-transplantation and to learn how to control their survival and migration proliferation/differentiation in the hostile pathologic environment. Future research should focus on methods of isolation, optimal dosage, appropriate cell type, route of administration, role of tissue-derived factors and supportive endogenous stimulation. PMID:22731756

  2. Functional Status of Elderly Adults Before and After Interventions for Critical Limb Ischemia

    PubMed Central

    Vogel, Todd R.; Petroski, Gregory F.; Kruse, Robin L.

    2014-01-01

    Objective The impact of interventions for Critical Limb Ischemia (CLI) on functional status in the elderly remains unclear. Open and endovascular procedures were evaluated. Methods Medicare inpatient claims were linked with nursing home assessment data to identify elective admissions for lower extremity procedures for CLI. A functional impairment score (0-28; higher scores indicating greater impairment) based on residents' need for assistance with self-care activities, walking, and locomotion was calculated before and after interventions. Hierarchical modeling determined the effect of the surgery on residents' function, controlling for comorbidity, cognition, and pre-hospital function. Results 352 and 350 patients underwent open and endovascular procedures, respectively (rest pain: 84; ulceration: 351; and gangrene: 267). Hospitalization was associated with a significant worsening in function following both procedures. Disease severity was associated with the amount of initial decline but not with the rate of recovery (p>.35). Residents who received open surgery improved more quickly following hospital discharge (p=.011). Conclusions In the frail elderly, open and endovascular procedures for CLI were associated with similar initial declines in functional status, suggesting that compared with open procedures, less invasive endovascular procedures were not associated with maintaining baseline function. In this select population, endovascular procedures for CLI were not associated with improved functional status over time compared to open. Six months post-hospital, patients who received traditional open bypass had significantly better functional status than those who received endovascular procedures for all CLI diagnoses. Further analysis is required to assist stakeholders in performing procedures most likely to preserve functional status in the frail elderly and nursing home population. PMID:24139567

  3. Outcomes of Infrainguinal Revascularizations with Endovascular First Strategy in Critical Limb Ischemia

    SciTech Connect

    Jens, Sjoerd; Conijn, Anne P. Frans, Franceline A.; Nieuwenhuis, Marieke B. B. Met, Rosemarie; Koelemay, Mark J. W. Legemate, Dink A.; Bipat, Shandra Reekers, Jim A.

    2015-06-15

    PurposeThis study was designed to study the outcome of infrainguinal revascularization in patients with critical limb ischemia (CLI) in an institution with a preference towards endovascular intervention first in patients with poor condition, unfavourable anatomy for surgery, no venous material for bypass, and old age.MethodsA prospective, observational cohort study was conducted between May 2007 and May 2010 in patients presenting with CLI. At baseline, the optimal treatment was selected, i.e., endovascular or surgical treatment. In case of uncertainty about the preferred treatment, a multidisciplinary team (MDT) was consulted. Primary endpoints were quality of life and functional status 6 and 12 months after initial intervention, assessed by the VascuQol and AMC Linear Disability Score questionnaires, respectively.ResultsIn total, 113 patients were included; 86 had an endovascular intervention and 27 had surgery. During follow-up, 41 % underwent an additional ipsilateral revascularisation procedure. For the total population, and endovascular and surgery subgroups, the VascuQol sum scores improved after 6 and 12 months (p < 0.01 for all outcomes) compared with baseline. The functional status improved (p = 0.043) after 12 months compared with baseline for the total population. Functional status of the surgery subgroup improved significantly after 6 (p = 0.031) and 12 (p = 0.044) months, but not that of the endovascular subgroup.ConclusionsOverall, the strategy of performing endovascular treatment first in patients with poor condition, unfavourable anatomy for surgery, no venous material for bypass, and old age has comparable or even slightly better results compared with the BASIL trial and other cohort studies. All vascular groups should discuss whether their treatment strategy should be directed at treating CLI patients preferably endovascular first and consider implementing an MDT to optimize patient outcomes.

  4. Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia.

    PubMed

    Li, Yaqian; Liu, Wei; Liu, Fei; Zeng, Yang; Zuo, Simin; Feng, Siyu; Qi, Chunxiao; Wang, Bingjie; Yan, Xiaojun; Khademhosseini, Ali; Bai, Jing; Du, Yanan

    2014-09-16

    The promise of cell therapy for repair and restoration of damaged tissues or organs relies on administration of large dose of cells whose healing benefits are still limited and sometimes irreproducible due to uncontrollable cell loss and death at lesion sites. Using a large amount of therapeutic cells increases the costs for cell processing and the risks of side effects. Optimal cell delivery strategies are therefore in urgent need to enhance the specificity, efficacy, and reproducibility of cell therapy leading to minimized cell dosage and side effects. Here, we addressed this unmet need by developing injectable 3D microscale cellular niches (microniches) based on biodegradable gelatin microcryogels (GMs). The microniches are constituted by in vitro priming human adipose-derived mesenchymal stem cells (hMSCs) seeded within GMs resulting in tissue-like ensembles with enriched extracellular matrices and enhanced cell-cell interactions. The primed 3D microniches facilitated cell protection from mechanical insults during injection and in vivo cell retention, survival, and ultimate therapeutic functions in treatment of critical limb ischemia (CLI) in mouse models compared with free cell-based therapy. In particular, 3D microniche-based therapy with 10(5) hMSCs realized better ischemic limb salvage than treatment with 10(6) free-injected hMSCs, the minimum dosage with therapeutic effects for treating CLI in literature. To the best of our knowledge, this is the first convincing demonstration of injectable and primed cell delivery strategy realizing superior therapeutic efficacy for treating CLI with the lowest cell dosage in mouse models. This study offers a widely applicable cell delivery platform technology to boost the healing power of cell regenerative therapy. PMID:25197069

  5. Proximal tubule sphingosine kinase-1 has a critical role in A1 adenosine receptor-mediated renal protection from ischemia

    PubMed Central

    Park, Sang Won; Kim, Mihwa; Kim, Joo Yun; Brown, Kevin M.; Haase, Volker H.; D’Agati, Vivette D.; Lee, H. Thomas

    2012-01-01

    Renal ischemia reperfusion injury is a major cause of acute kidney injury. We previously found that renal A1 adenosine receptor (A1AR) activation attenuated multiple cell death pathways including necrosis, apoptosis and inflammation. Here, we tested whether induction of cytoprotective sphingosine kinase (SK)-1 and sphingosine-1 phosphate (S1P) synthesis might be the mechanism of protection. A selective A1AR agonist (CCPA) increased the synthesis of S1P and selectively induced SK-1 in mouse kidney and HK-2 cells. This agonist failed to protect SK1-knockout but protected SK2-knockout mice against renal ischemia reperfusion injury indicating a critical role of SK1 in A1AR-mediated renal protection. Inhibition of SK prevented A1AR-mediated defense against necrosis and apoptosis in HK-2 cells. A selective S1P1R antagonist (W146) and global in vivo gene knockdown of S1P1Rs with small interfering RNA completely abolished the renal protection provided by CCPA. Mice selectively deficient in renal proximal tubule S1P1Rs (S1P1Rflox/flox PEPCKCre/−) were not protected against renal ischemia reperfusion injury by CCPA. Mechanistically, CCPA increased nuclear translocation of hypoxia inducible factor-1α in HK-2 cells and selective hypoxia inducible factor-1α inhibition blocked A1AR-mediated induction of SK1. Thus, proximal tubule SK-1 has a critical role in A1AR-mediated protection against renal ischemia reperfusion injury. PMID:22695326

  6. [Procedures in critical ischemia of the legs in non-emergency situations].

    PubMed

    Devin, R; Ciosi, G; Cormier, J M; Espinoza, H; Hodara, M; Howette, L; Jimeno, M T; Kasbarian, M; Laurian, C; Long, A

    1990-01-01

    Our experience with 91 operated cases in 84 patients (47 men, 37 women) relates essentially to arterial diseases resulting from overloading and diabetic arteriopathy. Diagnosis of critical ischemia is easy in clinical conditions, but it is advisable to rely on universally recognized hemodynamic standards to define this condition. Ankle pressure should be less than 400 mmHg and the Doppler trace flat or barely perceptible. Patients in our series had a mean ankle pressure of 32.4 mmHg. Local examination can determine the extent of gangrene, whereas general examination detects numerous, often associated defects diabetes, coronary artery disease, rhythm disorders, arterial hypertension, etc. As far as possible, these defects are to be corrected before surgery. X-ray examination (M. Kasbarian) is frequently done in conjunction with conventional aorto-arteriography and digital angiography. The later technique allows arteries to be visualized which are not seen with the conventional technique. The x-ray examination will indicate whether revascularization is feasible, although it cannot show whether it will be efficient. In our series, opacification of the plantar arches was predictive neither of success nor failure. But do tests exist which can predict the success of a revascularization attempt? It would be necessary to be able to estimate ankle pressure after the operation, and several methods have tried to do this. TcPO2 would seem to be a good examination. The possibilities of nuclear magnetic resonance are being studied, and the results thus far are promising. Preoperative explorations are carried out in a different situation. Arteriography performed in the operating room is a simple act which can reveal a usable downstream bed not indicated in preoperative X-rays, although it provides no hemodynamic data. Measurement of peripheral resistances would appear to be a very good predictive examination. Flow measurements by infusion or electronic flowmeter also seem to be

  7. Discharge Destination after Elective Femoropopliteal Bypass in Patients without Critical Ischemia.

    PubMed

    Kauvar, David S; Osborne, Candice L

    2016-05-01

    Femoropopliteal bypass (FPB) remains a widely accepted treatment option for symptomatic leg ischemia, even in patients without features of critical limb ischemia (CLI). These patients are revascularized to improve symptoms of exertional limb pain and the goal of such treatment is to increase their ability to ambulate within the community. Therefore, the anticipated initial discharge disposition for a patient without CLI undergoing FPB is back to their home. This study examined the disposition at initial discharge of such patients. Data from the 2012 National Surgical Quality Improvement Program registry was queried for all elective FPB performed in patients without CLI. Analysis was limited to patients surviving to initial discharge who were living independently at home before surgery. Initial disposition was defined as to HOME or to a FACILITY (either rehabilitation or skilled nursing); these constituting the study groups. Univariate analysis and multivariable logistic regression were performed to identify patient risk factors for failure to discharge to home. In-hospital and postoperative events were also recorded and compared. Significance was defined at P ≤ 0.05. In National Surgical Quality Improvement Program 2012, 1060 cases of elective FPB in patients without CLI were found. The mean± SD age of the population was 65 ± 9 years; 359 (34%) of patients were female; 198 (19%) had a reported race other than white; and most (893, 84%) had hypertension. 60 (6%) patients failed to discharge to home (26 to rehabilitation, 34 to skilled nursing). On univariate analysis, age (FACILITY 68 ± 11 years vs HOME 65 ± 9 years, P = 0.009), female gender (55% vs 37%, P < 0.001), nonwhite race (30% vs 18%, P = 0.007), and a history of diabetes (48% vs 33%, P = 0.01), dialysis (5% vs 1.3%, P = 0.02) congestive heart failure (5% vs 1.1%, P = 0.01), or a stroke (cerebrovascular accident, 5% vs 2.6%, P = 0.01) were found to predict failure to discharge to home. On multivariate

  8. Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial

    PubMed Central

    Spreen, Marlon I.; Martens, Jasper M.; Hansen, Bettina E.; Knippenberg, Bob; Verhey, Elke; van Dijk, Lukas C.; de Vries, Jean-Paul P.M.; Vos, Jan-Albert; de Borst, Gert Jan; Vonken, Evert-Jan P.A.; Wever, Jan J.; Statius van Eps, Randolph G.; Mali, Willem P.Th.M.

    2016-01-01

    Background— Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions. Methods and Results— Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia–related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (P=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03). Conclusions— In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289. PMID:26861113

  9. Endovascular recanalization of infrapopliteal occlusions in patients with critical limb ischemia

    PubMed Central

    Singh, Gagan D.; Armstrong, Ehrin J.; Yeo, Khung-Keong; Singh, Satinder; Westin, Gregory G.; Pevec, William C.; Dawson, David L.; Laird, John R.

    2014-01-01

    Background Endovascular therapies are increasingly used for treatment of critical limb ischemia (CLI). Infrapopliteal (IP) occlusions are common in CLI, and successful limb salvage may require restoration of arterial flow in the distribution of a chronically occluded vessel. We sought to describe the procedural characteristics and outcomes of patients with IP occlusions who underwent endovascular intervention for treatment of CLI. Methods All patients with IP interventions for treatment of CLI from 2006 to 2012 were included. Angiographic and procedural data were compared between patients who underwent intervention for IP occlusions vs IP stenosis. Restenosis was determined by Doppler ultrasound imaging. Limb salvage was the primary end point of the study. Additional end points included primary patency, primary assisted patency, secondary patency, occlusion crossing success, procedural success, and amputation-free survival. Results A total of 187 patients with CLI underwent interventions for 356 IP lesions, and 77 patients (41%) had interventions for an IP occlusion. Patients with an intervention for IP occlusion were more likely to have zero to one vessel runoff (83% vs 56%; P < .001) compared with interventions for stenosis. Compared with IP stenoses, IP occlusions were longer (118 ± 86 vs 73 ± 67 mm; P < .001) and had a smaller vessel diameter (2.5 ± 0.8 vs 2.7 ± 0.5 mm; P =.02). Wire crossing was achieved in 83% of IP occlusions, and the overall procedural success for IP occlusions was 79%. The overall 1-year limb salvage rate was 84%. Limb salvage was highest in the stenosis group, slightly lower in the successful occlusion group, and lowest in the failed occlusion group (92% vs 75% vs 58%, respectively; P = .02). Unsuccessfully treated IP occlusions were associated with a significantly higher likelihood of major amputation (hazard ratio, 5.79; 95% confidence interval, 1.89–17.7) and major amputation or death (hazard ratio, 2.69; 95% confidence interval

  10. Elevated Blood Urea Nitrogen is Associated With Critical Limb Ischemia in Peripheral Arterial Disease Patients

    PubMed Central

    Gary, Thomas; Pichler, Martin; Schilcher, Gernot; Hafner, Franz; Hackl, Gerald; Rief, Peter; Eller, Philipp; Brodmann, Marianne

    2015-01-01

    Abstract As renal function is often impaired in atherosclerosis patients, accelerating atherosclerosis per se and creating a vicious cycle, we investigated the association of blood urea nitrogen (BUN) and critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients. Our cross-sectional study included 1521 PAOD patients, with normal and impaired renal function treated at our institution from 2005 to 2010. Patients on renal replacement therapy were excluded. The cohort was divided into tertiles according to the serum BUN levels. An optimal cutoff value for the continuous BUN was calculated by applying a receiver-operating curve analysis to discriminate between CLI and non-CLI. In our cohort, CLI increased significantly with an increase in BUN (13.1% in the first tertile, 18.7% in the second tertile, 29.0% in the third tertile, P for trend <0.001). A BUN of 17.7 mg/dL was identified as an optimal cutoff. Accordingly, there were 2 groups of patients: 636 patients with BUN ≤ 17.7 and 885 patients with BUN > 17.7. CLI was more frequent in BUN > 17.7 patients (342 [38.6%]) than in BUN ≤ 17.7 patients (134 [21.1%]) (P < 0.001); the same applied to prior myocardial infarction (45 [5.1%] vs 15 [2.4%], P = 0.007) and congestive heart failure (86 [9.7%] vs 31 [4.9%], P < 0.001). A BUN > 17.7 was associated with an odds ratio of 1.6 (95% confidence interval: 1.3–1.9, P < 0.001) for CLI even after the adjustment for other established vascular risk factors such as age ≥75 and type 2 diabetes. An increased BUN is significantly associated with a high risk for CLI and other vascular endpoints. The BUN is an easily determinable, broadly available, and inexpensive marker that could be used to identify patients at high risk for vascular endpoints.

  11. Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia

    PubMed Central

    Jeon, Eui-Yong; Cho, Young Kwon; Yoon, Dae Young; Kim, Dae Jung; Woo, Jeong Joo

    2016-01-01

    PURPOSE We aimed to evaluate the clinical usefulness and outcome of angiosome-oriented percutaneous transluminal angioplasty (IP-PTA) and its clinical outcome for isolated infrapopliteal lesions in diabetic critical limb ischemia. METHODS We retrospectively reviewed 70 patients (82 limbs) with diabetic critical limb ischemia who had localized disease at the level of the infrapopliteal artery. Patients underwent IP-PTA between January 2011 and December 2013 and were followed up for a mean of 13 months. The primary target arterial lesions were chosen according to the angiosome concept. We evaluated clinical findings, technical success, and patients’ clinical outcome. The angiographic outcome of IP-PTA was assessed using the angiosome score. We analyzed the relationship between the angiosome score and the amputation rate. RESULTS There were 69 anterior tibial artery (ATA) lesions, 70 posterior tibial artery (PTA) lesions, and 58 peroneal artery (PA) lesions. The primary target arteries were the ATA (n=43), PTA (n=26), PA (n=2), and ATA + PTA (n=11). We divided the treated limbs into target (n=63) and nontarget (n=19) groups. The overall initial technical success rate was 91.4%. Successful wound healing rates were 87.3% (55/63) and 47.3% (9/19) in the target and nontarget groups, respectively (P < 0.05). CONCLUSION Angiosome-oriented primary targeted IP-PTA shows a highly effective treatment outcome in diabetic critical limb ischemia. In cases with inadequate angioplastic results of the target artery, IP-PTA of the nontarget artery should be recommended to improve the limb salvage rates. PMID:26573976

  12. Silent Ischemia

    MedlinePlus

    ... Vulnerable Plaque Silent Ischemia | Share Related terms: ischemia, restricted blood flow Ischemia is a condition where the flow of ... used to diagnose silent ischemia: An exercise stress test can show blood flow through your coronary arteries in response to exercise. ...

  13. Angioseal use after antegrade femoral arteriotomy in patients undergoing percutaneous revascularization for critical limb ischemia: a case series.

    PubMed

    Biondi-Zoccai, Giuseppe G L; Fusaro, Massimiliano; Tashani, Abdulkafi; Mollichelli, Nadia; Medda, Massimo; De Giacobbi, Graziella; Inglese, Luigi

    2007-06-12

    Antegrade femoral artery access is commonly used for percutaneous transluminal revascularization of ipsilateral lower limbs in patients with critical limb ischemia. While hemostasis at the end of the procedure can be achieved by manual compression, this may lead to an increase in local vascular complications. Femoral artery closure devices, such as the Angioseal collagen plug and anchor device, have been approved and shown of benefit after retrograde femoral artery catheterization. To date, there are however no data on the use of such arteriotomy closure device after antegrade femoral access. We hereby report a case series of five patients in whom Angioseal was successfully used after antegrade femoral puncture and below-the-knee percutaneous transluminal angioplasty. In all cases the device enabled immediate and complete hemostasis without major complications, despite the intense antithrombotic regimen, including heparin, aspirin, and clopidogrel in all patients, as well as glycoprotein IIb/IIIa inhibitors (in two patients) and fibrinolytic therapy (in one). PMID:17052791

  14. Clinical Outcomes After Endovascular Treatment of Superficial Femoral Disease in Patients With Disabling Claudication and Critical Limb Ischemia: Midterm Analysis

    PubMed Central

    Misselt, A. J.; Zielinski, M. D.; Garcia Medina, O. I.; Oderich, G.; Bjarnason, H.; McKusick, M. A.; Misra, Sanjay

    2015-01-01

    We present the midterm clinical outcomes and predictors of balloon angioplasty and stent placement in atherosclerotic femoropopliteal (FP) arterial disease. Between January 2002 and August 2006, 155 patients (men = 56%; 71.4 ± 10.5 years) underwent 171 FP angioplasty or stent for claudication (n = 82, 54%) or critical limb ischemia ([CLI] n = 70, 46%). Follow-up was obtained through September 30, 2009. The average follow-up was 3.25 ± 1.73 years. In claudicants versus CLI, the 12-month patency for TransAtlantic InterSociety Consensus II (TASC II) classification (TASC A/B) was 93% versus 80%, respectively, and TASC C/D 83% versus 80%. At 3 years, TASC A/B was 82% versus 80%, respectively, and TASC C/D was 56% versus 80%, respectively. The predictor of clinical failure in claudicants was chronic renal insufficiency (CRI) and in CLI, the predictor of amputation was hyperlipidemia. PMID:21873349

  15. Early results from an angiosome-directed open surgical technique for venous arterialization in patients with critical lower limb ischemia

    PubMed Central

    Houlind, Kim; Christensen, Johnny; Hallenberg, Christian; Jepsen, Jørn M.

    2013-01-01

    Background Patients with critical lower limb ischemia without patent pedal arteries cannot be treated by the conventional arterial reconstruction. Venous arterialization has been suggested to improve limb salvage in this subgroup of patients but has not gained wide acceptance. We report our early experience after implementing deep and superficial venous arterialization of the lower limb. Materials and methods Ten patients with critical ischemia and without crural or pedal arteries available for conventional bypass surgery or angioplasty were treated with distal venous arterialization. Inflow was from the most distal unobstructed segment. Run-off was the dorsal pedal venous arch (n=5), the dorsal pedal venous arch and a concomitant vein of the posterior tibial artery (n=3), or the dorsal pedal venous arch and a concomitant vein of the common plantar artery (n=2) depending on the location of the ischemic lesion. Venous valves were destroyed using antegrade valvulotomes, guide wires, knob needles, or retrograde valvulotomes via an extra incision. Results Seven of the operated limbs were amputated after 23 (1–256) days (median [range]). The main reasons for amputation were lack of healing of either the original wound, of incisional wounds on the foot, or persisting pain at rest. In three cases, the bypass was open at the time of amputation. Two patients experienced complete wound healing after 231 and 342 days, respectively. By the end of follow-up, the last patient was ambulating with slow wound healing but without pain 309 days after surgery. Conclusion Venous arterialization may be used as a treatment of otherwise unsalveable limbs. The success rate is, however, limited. Technical optimization of the technique is warranted. PMID:24358432

  16. Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion

    PubMed Central

    Zou, Ning; Ao, Lihua; Cleveland, Joseph C.; Yang, Xiaoping; Su, Xin; Cai, Guang-Yun; Banerjee, Anirban; Fullerton, David A.; Meng, Xianzhong

    2010-01-01

    Previous studies showed that Toll-like receptor 4 (TLR4) modulates the myocardial inflammatory response to ischemia-reperfusion injury, and we recently found that cytokines link TLR4 to postischemic cardiac dysfunction. Although TLR4 can be activated in cultured cells by endogenous agents including heat shock protein 70, how it is activated during myocardial ischemia-reperfusion is unknown. In the present study, we examined 1) whether heat shock cognate protein 70 (HSC70), which is constitutively expressed in the myocardium, is released during ischemia-reperfusion; 2) whether extracellular HSC70 induces the myocardial inflammatory response and modulates cardiac function; and 3) whether HSC70 exerts these effects via TLR4. We subjected isolated mouse hearts to global ischemia-reperfusion via the Langendorff technique. Immunoblotting and immunostaining detected the release of HSC70 from the myocardium during reperfusion. Treatment with an antibody specific to HSC70 suppressed myocardial cytokine expression and improved cardiac functional recovery after ischemia-reperfusion. Recombinant HSC70 induced NF-κB activation and cytokine expression and depressed myocardial contractility in a TLR4-dependent manner. These effects required the substrate-binding domain of HSC70. Fluorescence resonance energy transfer analysis of isolated macrophages demonstrated that extracellular HSC70 interacts with TLR4. Therefore, this study demonstrates for the first time that 1) the myocardium releases HSC70 during ischemia-reperfusion, 2) extracellular HSC70 contributes to the postischemic myocardial inflammatory response and to cardiac dysfunction, 3) HSC70 exerts these effects through a TLR4-dependent mechanism, and 4) the substrate-binding domain of HSC70 is required to induce these effects. Thus extracellular HSC70 plays a critical role in regulating the myocardial innate immune response and cardiac function after ischemia-reperfusion. PMID:18441202

  17. Blood Oxygenation Level-Dependent CMR-Derived Measures in Critical Limb Ischemia and Changes With Revascularization

    PubMed Central

    Bajwa, Adnan; Wesolowski, Roman; Patel, Ashish; Saha, Prakash; Ludwinski, Francesca; Ikram, Mohammed; Albayati, Mostafa; Smith, Alberto; Nagel, Eike; Modarai, Bijan

    2016-01-01

    Background Use of blood oxygenation level-dependent cardiovascular magnetic resonance (BOLD-CMR) to assess perfusion in the lower limb has been hampered by poor reproducibility and a failure to reliably detect post-revascularization improvements in patients with critical limb ischemia (CLI). Objectives This study sought to develop BOLD-CMR as an objective, reliable clinical tool for measuring calf muscle perfusion in patients with CLI. Methods The calf was imaged at 3-T in young healthy control subjects (n = 12), age-matched control subjects (n = 10), and patients with CLI (n = 34). Signal intensity time curves were generated for each muscle group and curve parameters, including signal reduction during ischemia (SRi) and gradient during reactive hyperemia (Grad). BOLD-CMR was used to assess changes in perfusion following revascularization in 12 CLI patients. Muscle biopsies (n = 28), obtained at the level of BOLD-CMR measurement and from healthy proximal muscle of patients undergoing lower limb amputation (n = 3), were analyzed for capillary-fiber ratio. Results There was good interuser and interscan reproducibility for Grad and SRi (all p < 0.0001). The ischemic limb had lower Grad and SRi compared with the contralateral asymptomatic limb, age-matched control subjects, and young control subjects (p < 0.001 for all comparisons). Successful revascularization resulted in improvement in Grad (p < 0.0001) and SRi (p < 0.0005). There was a significant correlation between capillary-fiber ratio (p < 0.01) in muscle biopsies from amputated limbs and Grad measured pre-operatively at the corresponding level. Conclusions BOLD-CMR showed promise as a reliable tool for assessing perfusion in the lower limb musculature and merits further investigation in a clinical trial. PMID:26821631

  18. The BEST-CLI trial: a multidisciplinary effort to assess which therapy is best for patients with critical limb ischemia.

    PubMed

    Farber, Alik; Rosenfield, Kenneth; Menard, Matthew

    2014-09-01

    Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease and is associated with a significant risk of limb loss. It is currently treated with limb revascularization by a variety of specialists. Although both open vascular bypass and endovascular therapy are offered to patients with infrainguinal peripheral arterial disease and CLI, significant disagreement exists as to which therapy works best in candidates for both types of intervention. Persistent clinical equipoise in combination with a paucity of comparative effectiveness data to guide treatment of CLI has led to a multidisciplinary effort to organize the Best Endovascular versus Best Surgical Therapy in patients with CLI (BEST-CLI) trial. The BEST-CLI trial is a pragmatic, multicenter, open label, randomized trial that compares best endovascular therapy with best open surgical treatment in patients eligible for both treatments. This trial is highly innovative in both its design and its collaborative nature. BEST-CLI aims to provide urgently needed clinical guidance for CLI management by using (1) a pragmatic design comparing the effectiveness of established techniques while allowing for the introduction of newer therapies as they become available; (2) a novel primary end point that includes limb amputation rates, repeat intervention, and mortality; (3) a multidisciplinary structure that fosters cooperation among interventional cardiologists, interventional radiologists, vascular surgeons, and vascular medicine specialists; and (4) novel techniques to evaluate the cost-effectiveness and quality-of-life outcomes of the 2 treatment strategies being tested. PMID:25241324

  19. Association of Diabetes and Hemodialysis With Ankle Pressure and Ankle-Brachial Index in Japanese Patients With Critical Limb Ischemia

    PubMed Central

    Takahara, Mitsuyoshi; Kaneto, Hideaki; Iida, Osamu; Katakami, Naoto; Matsuoka, Taka-aki; Ikeda, Masahiko; Shimomura, Iichiro

    2012-01-01

    OBJECTIVE To investigate whether diabetes and regular hemodialysis are associated with false elevation of ankle systolic blood pressure and ankle-brachial systolic pressure index (ABI) because of their arterial calcification in patients with critical limb ischemia (CLI). RESEARCH DESIGN AND METHODS We recruited 269 Japanese patients who underwent endovascular therapy for CLI. Ankle systolic blood pressure and ABI were assessed before endovascular therapy. Arterial stenosis and calcification were evaluated angiographically. We investigated the associations among clinical comorbidities, arterial calcification, and measurements of ankle systolic blood pressure and ABI. RESULTS Ankle systolic blood pressure was 85 ± 56 mmHg, and ABI was 0.59 ± 0.37. Arterial calcification was observed in 69% of the patients. The prevalence of diabetes and regular hemodialysis was 71 and 47%. Diabetes and regular hemodialysis were both significantly associated with the presence of arterial calcification; their adjusted odds ratios were 2.33 (P = 0.01) and 7.40 (P < 0.01), respectively. However, there was no significant difference in ankle systolic blood pressure or ABI level between those with and without these comorbidities. Furthermore, the presence of arterial calcification was not associated with ankle systolic blood pressure or ABI level, whereas arterial stenoses of all segments in the lower body had independent associations with reduced ankle systolic blood pressure and ABI level. CONCLUSIONS Diabetes and regular hemodialysis were significantly associated with arterial calcification, but not with elevated measurements of ankle systolic blood pressure or ABI, in CLI patients. PMID:22723344

  20. The Use of Below-Knee Percutaneous Transluminal Angioplasty in Arterial Occlusive Disease Causing Chronic Critical Limb Ischemia

    SciTech Connect

    Loefberg, Ann-Marie; Loerelius, Lars-Erik; Karacagil, Sadettin; Westman, Bo; Almgren, Bo; Berqgvist, David

    1996-09-15

    Purpose: To determine the efficacy, safety and long-term results of crural artery percutaneous transluminal angioplasty (PTA) in limbs with chronic critical limb ischemia (CLI). Methods: Patients undergoing crural artery PTA due to CLI were followed at regular clinic visits with ankle brachial pressure index (ABPI) measurements. PTA of the crural arteries was attempted either alone (n= 39) or in combination with PTA of the superficial and/or popliteal artery (n= 55) in 86 limbs (82 patients and 94 procedures) presenting with CLI. The ages of patients ranged from 37 to 94 years (mean 72 years). The indications for PTA were rest pain in 10 and ulcer/gangrene in 84 limbs.Results: A technically successful PTA with at least one crural level was achieved in 88% of cases (n= 83). Cumulative primary clinical success rates at 6, 12, 24, and 36 months were 55%, 51%, 36%, and 36%, respectively. Cumulative secondary clinical success and limb salvage rates at 36 months were 44% and 72%, respectively. Conclusion: PTA of the crural arteries might be considered the primary choice of treatment in patients with CLI and distal lesions with localized stenosis or segmental short occlusions.

  1. Chronic critical lower-limb ischemia: prospective trial of angioplasty with 1-36 months follow-up.

    PubMed

    Matsi, P J; Manninen, H I; Suhonen, M T; Pirinen, A E; Soimakallio, S

    1993-08-01

    To determine the utility of percutaneous transluminal angioplasty (PTA) in the treatment of chronic critical lower-limb ischemia, a prospective study of 103 consecutive patients (117 limbs) was performed. Patients underwent PTA for a total of 209 lesions in the iliac (n = 4), femoropopliteal (n = 121), and infrapopliteal (n = 84) arteries and were followed up for 1-36 months (mean, 12 months). The primary technical success rate was 92% for stenosis and 80% for occlusion. Survival analysis with the Kaplan-Meier method revealed 1-, 2-, and 3-year limb salvage rates of 56%, 49%, and 49%, respectively. The following factors correlated favorably with limb salvage in Cox multiple regression analyses: a small number of diseased lower-limb vessels (one to five vs six to eight) and treated lesions per limb (one or two vs three to five), achieved peripheral runoff (one to three patent calf vessels vs none), and an occlusion as the successfully treated target lesion (instead of stenosis). PMID:8327682

  2. Influence of risk factors and comorbidities on the successful therapy and survival of patients with critical limb ischemia

    PubMed Central

    CONSTANTINESCU, MIHAELA IOANA; CONSTANTINESCU, DAN PETRU; CHIŞ, BOGDAN; ANDERCOU, AUREL; MIRONIUC, ION AUREL

    2013-01-01

    Background Critical limb ischemia (CLI) is associated with an increased risk of limb amputation, low quality of life and cardiovascular death. The aim of this study is to identify the prognostic factors of mortality, revascularization failure and amputation failure, as part of risk factors for athero-sclerosis and comorbidities. Patients and methods We examined 198 patients operated for CLI. Cox analysis was performed to discern the factors that were associated with failure of initial surgical therapy and death. Results For survival analysis, a significant model emerged with hypertension (p=0.00), cardiac comorbidities (p=0.00), renal comorbidities (p=0.04) and respiratory comorbidities (p=0.02) as significant predictors. Regarding the time to amputation failure, there was a significant model with insulin treated diabetes (p=0.00), coronary artery disease (p=0.02) and cerebrovascular disease (p=0.05) as significant predictors. Conclusions Significant predictors for mortality in CLI patients are high risk hypertension, severe coronary artery disease, renal failure requiring dialysis and chronic obstructive pulmonary disease. The association of these prognostic factors results in a proportional decrease of survival. The predictors for amputation failure were, in addition to local factors, insulin treated diabetes, coronary artery disease and cerebrovascular disease. The revascularization for limb salvage depends on the correct indication and accurate surgical technique. PMID:26527918

  3. Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia.

    PubMed

    Kibbe, M R; Hirsch, A T; Mendelsohn, F O; Davies, M G; Pham, H; Saucedo, J; Marston, W; Pyun, W-B; Min, S-K; Peterson, B G; Comerota, A; Choi, D; Ballard, J; Bartow, R A; Losordo, D W; Sherman, W; Driver, V; Perin, E C

    2016-03-01

    VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5 ± 17.8 versus 36.6 ± 24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients. PMID:26649448

  4. Local Gene Transfer and Expression Following Intramuscular Administration of FGF-1 Plasmid DNA in Patients With Critical Limb Ischemia

    PubMed Central

    Baumgartner, Iris; Chronos, Nicolas; Comerota, Anthony; Henry, Timothy; Pasquet, Jean-Paul; Finiels, François; Caron, Anne; Dedieu, Jean-François; Pilsudski, Richard; Delaère, Pia

    2009-01-01

    NV1FGF is an expression plasmid encoding sp.FGF-121–154 currently under investigation for therapeutic angiogenesis in clinical trials. NV1FGF plasmid distribution and transgene expression following intramuscular (IM) injection in patients is unknown. The study involved six patients with chronic critical limb ischemia (CLI) planned to undergo amputation. A total dose of 0.5, 2, or 4 mg NV1FGF was administered as eight IM injections (0.006, 0.25, or 0.5 mg per injection) 3–5 days before amputation. Injected sites (30 cm3) were divided into equally sized smaller pieces to assess spatial distribution of NV1FGF sequences (PCR), NV1FGF mRNA (reverse transcriptase-PCR), and fibroblast growth factor-1 (FGF-1)-expressing cells (immunohistochemistry). Data indicated gene expression at all doses. The distribution area was within 5–12 cm for NV1FGF sequences containing the expression cassette, up to 5 cm for NV1FGF mRNA, and up to 3 cm for FGF-1-expressing myofibers. All FGF receptors were detected indicating robust potential for bioactivity after NV1FGF gene transfer. Circulating levels of NV1FGF sequences were shown to decrease within days after injection. Data support demonstration of plasmid-mediated gene transfer and expression in muscles from patients with CLI. FGF-1 expression was shown to be limited to injection sites, which supports the concept of multiple-site injection for therapeutic use. PMID:19240689

  5. Early Results of Clinical Application of Autologous Whole Bone Marrow Stem Cell Transplantation for Critical Limb Ischemia with Buerger's Disease.

    PubMed

    Heo, Seon-Hee; Park, Yoong-Seok; Kang, Eun-Suk; Park, Kwang-Bo; Do, Young-Soo; Kang, Kyung-Sun; Kim, Dong-Ik

    2016-01-01

    Our goal was to evaluate early results of the clinical application of autologous whole bone marrow stem cell transplantation (AWBMSCT) for critical limb ischemia (CLI) in patients with Buerger's disease. We retrospectively analyzed the data of 58 limbs of 37 patients (mean age, 43.0 years; range, 28-63 years; male, 91.9%) with Buerger's disease with CLI who were treated with AWBMSCT from March 2013 to December 2014. We analyzed Rutherford category, pain score, pain-free walking time (PFWT), total walking time (TWT), ankle brachial pressure index (ABPI), and toe brachial pressure index (TBPI), and investigated wound healing and occurrence of unplanned amputations. The mean follow-up duration was 11.9 ± 7.2 months (range, 0.9-23.9 months) and 100%, 72.4%, and 74.1% of patients were available to follow-up 1, 3 and 6 months after AWBMST, respectively. At 6 months, patients demonstrated significant improvements in Rutherford category (P < 0.0001), pain score (P < 0.0001), PFWT (P < 0.0001) and TBPI (P < 0.0001). ABPI was increased compared to baseline, but the difference was not significant. A total of 76.5% ischemic wounds achieved complete or improved healing. AWBMSCT is a safe and effective alternative or adjunctive treatment modality to achieve clinical improvement in patients with CLI. PMID:26791280

  6. Prediction of Limb Salvage after Therapeutic Angiogenesis by Autologous Bone Marrow Cell Implantation in Patients with Critical Limb Ischemia

    PubMed Central

    Tara, Shuhei; Miyamoto, Masaaki; Takagi, Gen; Fukushima, Yoshimitsu; Kirinoki-ichikawa, Sonoko; Takano, Hitoshi; Takagi, Ikuyo; Mizuno, Hiroshi; Yasutake, Masahiro; Kumita, Shinichiro; Mizuno, Kyoichi

    2011-01-01

    Purpose: Despite advances in therapeutic angiogenesis by bone marrow cell implantation (BMCI), limb amputation remains a major unfavorable outcome in patients with critical limb ischemia (CLI). We sought to identify predictor(s) of limb salvage in CLI patients who received BMCI. Materials and Methods: Nineteen patients with CLI who treated by BMCI were divided into two groups; four patients with above-the-ankle amputation by 12 weeks after BMCI (amputation group) and the remaining 15 patients without (salvage group). We performed several blood-flow examinations before BMCI. Ankle-brachial index (ABI) was measured with the standard method. Transcutaneous oxygen tension (TcPO2) was measured at the dorsum of the foot, in the absence (baseline) and presence (maximum TcPO2) of oxygen inhalation. 99mtechnetium-tetrofosmin (99mTc-TF) perfusion index was determined at the foot and lower leg as the ratio of brain. Results: Maximum TcPO2 (p = 0.031) and 99mTc-TF perfusion index in the foot (p = 0.0068) was significantly higher in the salvage group than in the amputation group. Receiver operating characteristic (ROC) curve analysis identified maximum TcPO2 and 99mTc-TF perfusion index in the foot as having high predictive accuracy for limb salvage. Conclusion: Maximum TcPO2 and 99mTc-TF perfusion index in the foot are promising predictors of limb salvage after BMCI in CLI. PMID:23555423

  7. Results of distal revascularization in elderly patients for critical ischemia of the lower limbs.

    PubMed

    Illuminati, G; Calio, F G; Bertagni, A; Piermattei, A; Vietri, F; Martinelli, V

    1999-04-01

    Thirty eight patients over 75 years of age were operated upon of 40 distal arterial revascularizations for critical ischaemia of the lower limbs. Arterial reconstruction was proposed to ambulatory, self sufficient patients, with a patent artery of the leg or the foot in continuity with pedal arch, at arteriography. The revascularized artery was the peroneal in 14 cases, the anterior tibial in 11, the posterior tibial in 9, the dorsalis pedis in 5, and the external plantar artery in 1 case. Postoperative mortality was 2.6%. No postoperative arterial occlusion occurred and no postoperative amputation needed to be performed. The mean follow-up of 37 patients surviving operation was 21 months (ext. 2-52 months). At 36 months interval, patients' survival was 43%, primary patency rate was 57%, and limb salvage rate was 76%, at life-table analysis. Distal revascularization enables a good number of elderly patients in critical ischaemia of the lower limb, to enjoy an active, independent life, with a viable limb. PMID:10352735

  8. Three-Dimensional Rotational Angiography of the Foot in Critical Limb Ischemia: A New Dimension in Revascularization Strategy

    SciTech Connect

    Jens, Sjoerd; Lucatelli, Pierleone; Koelemay, Mark J. W.; Marquering, Henk A. Reekers, Jim A.

    2013-06-15

    Purpose. To evaluate the additional value of three-dimensional rotational angiography (3DRA) of the foot compared with digital subtraction angiography (DSA) in patients with critical limb ischemia (CLI). Technique. For 3DRA, the C-arm was placed in the propeller position with the foot in an isocentric position. The patient's unaffected foot was positioned in a footrest outside the field of view. For correct timing of 3DRA, the delay from contrast injection in the popliteal artery at the level of knee joint to complete pedal arterial enhancement was assessed using DSA. With this delay, 3DRA was started after injection of 15 ml contrast. Imaging of the 3DRA could directly be reconstructed and visualized.Materials and MethodsPatients undergoing 3DRA of the foot were prospectively registered. DSA and 3DRA images were scored separately for arterial patency and presence of collaterals. Treatment strategies were proposed based on DSA with and without the availability of 3DRA. Results. Eleven patients underwent 3DRA of the foot. One 3DRA was not included because the acquisition was focused on the heel instead of the entire foot. Diagnostic quality of 3DRA was good in all ten patients. 3DRA compared with DSA showed additional patent arteries in six patients, patent plantar arch in three patients, and collaterals between the pedal arteries in five patients. Additional information from 3DRA resulted in a change of treatment strategy in six patients. Conclusion, 3DRA of the foot contains valuable additional real-time information to better guide peripheral vascular interventions in patients with CLI and nonhealing tissue lesions.

  9. Alternative Techniques for Treatment of Complex Below-the Knee Arterial Occlusions in Diabetic Patients With Critical Limb Ischemia

    SciTech Connect

    Gandini, Roberto; Uccioli, Luigi; Spinelli, Alessio; Del Giudice, Costantino Ros, Valerio Da; Volpi, Tommaso; Meloni, Marco; Simonetti, Giovanni

    2013-02-15

    The purpose of this study was to describe alternative endovascular (EV) techniques and assess their feasibility and efficacy in minimizing failure rates in limb salvage for the treatment of complex below-the knee (BTK) occlusions that could not be crossed with a conventional antegrade access. Between December 2007 and November 2010, 1,035 patients (557 male) underwent EV treatment for critical limb ischemia in our institution. In 124 (12% [83 male], mean age 68.2 {+-} 0.5 years) patients, transfemoral antegrade revascularization attempt failed, and an alternative approach was used. Follow-up was performed at 1 and 6 months. Results were compared with 56 patients treated between November 2002 and November 2007, in whom conventional technique was unsuccessful and unconventional techniques were not adopted. Technical success was achieved in 119 (96%) patients. The limb-salvage rates were 96.8% and 83% at 1- and 6-month follow-up, respectively. Sixteen (12.9%) and 33 (26.6%) patients underwent reintervention at 1- and 6-month follow-up, respectively. Transcutaneous oxygen tension increased at 1 month (44.7 {+-} 1.1 vs. 15.7 {+-} 0.8 mmHg; p < 0.001) and remained stable at follow-up. Twenty (16.1%) patients required major amputation. Thirteen (10.4%) patients died during follow-up. In our previous experience, percutaneous transluminal angioplasty failure, amputation, and death rates were 10.9, 39.2, and 23.2%, respectively. Alternative techniques allowed a significant decrease of major amputation and death rates (p = 0.0001 and p = 0.02, respectively). The use of alternative techniques seems feasible in case of a failed antegrade BTK revascularization attempt and could minimize failure rates in the treatment of complex occlusions while providing satisfying clinical success rates at 6 months.

  10. Characterization of the Cellular Output of a Point-of-Care Device and the Implications for Addressing Critical Limb Ischemia

    PubMed Central

    Woodell-May, Jennifer E.; Tan, Matthew L.; King, William J.; Swift, Matthew J.; Welch, Zachary R.; Murphy, Michael P.; McKale, James M.

    2015-01-01

    Abstract Critical limb ischemia (CLI) is a terminal disease with high morbidity and healthcare costs due to limb loss. There are no effective medical therapies for patients with CLI to prevent amputation. Cell-based therapies are currently being investigated to address this unmet clinical need and have shown promising preliminary results. The purpose of this study was to characterize the output of a point-of-care cell separator (MarrowStim P.A.D. Kit), currently under investigation for the treatment of CLI, and compare its output with Ficoll-based separation. The outputs of the MarrowStim P.A.D. Kit and Ficoll separation were characterized using an automated hematology analyzer, colony-forming unit (CFU) assays, and tubulogenesis assays. Hematology analysis indicated that the MarrowStim P.A.D. Kit concentrated the total nucleated cells, mononuclear cells, and granulocytes compared with baseline bone marrow aspirate. Cells collected were positive for VEGFR-2, CD3, CD14, CD34, CD45, CD56, CD105, CD117, CD133, and Stro-1 antigen. CFU assays demonstrated that the MarrowStim P.A.D. Kit output a significantly greater number of mesenchymal stem cells and hematopoietic stem cells compared with cells output by Ficoll separation. There was no significant difference in the number of endothelial progenitor cells output by the two separation techniques. Isolated cells from both techniques formed interconnected nodes and microtubules in a three-dimensional cell culture assay. This information, along with data currently being collected in large-scale clinical trials, will help instruct how different cellular fractions may affect the outcomes for CLI patients. PMID:26634187

  11. Ischemia-modified albumin levels in the prediction of acute critical neurological findings in carbon monoxide poisoning.

    PubMed

    Daş, Murat; Çevik, Yunsur; Erel, Özcan; Çorbacioğlu, Şeref Kerem

    2016-04-01

    The aim of the study was to determine whether serum ischemia-modified albumin (IMA) levels in patients with carbon monoxide (CO) poisoning were higher compared with a control group of healthy volunteers. In addition, the study sought to determine if there was a correlation between serum IMA levels and carboxyhemoglobin (COHB) levels and other critical neurological findings (CNFs). In this prospective study, the IMA levels of 100 patients with CO poisoning and 50 control individuals were compared. In addition, the IMA and COHB levels were analyzed according to absence or presence CNFs in patients with CO poisoning. The levels of IMA (mg/dL) on admittance, and during the 1(st) hour and 3(rd) hour, in patients with CO poisoning (49.90 ± 35.43, 30.21 ± 14.81, and 21.87 ± 6.03) were significantly higher, compared with the control individuals (17.30 ± 2.88). The levels of IMA in the 6(th) hour were not higher compared with control individuals. The levels of IMA on admittance, and during the 1(st) hour, 3(rd) hour, and 6(th) hour, and COHB (%) levels in patients who had CNFs were higher compared with IMA levels and COHB levels in patients who had no CNFs (p < 0.001). However, when the multivariate model was created, it was observed that IMA level on admittance was a poor indicator for prediction of CNFs (odds ratio = 1.05; 95% confidence interval, 1.01-1.08). We therefore concluded that serum IMA levels could be helpful in the diagnosis of CO poisoning. However, we believe that IMA levels cannot be used to predict which patients will develop CNFs due to CO poisoning. PMID:27185603

  12. Therapeutic potential of sustained-release sodium nitrite for critical limb ischemia in the setting of metabolic syndrome.

    PubMed

    Polhemus, David J; Bradley, Jessica M; Islam, Kazi N; Brewster, Luke P; Calvert, John W; Tao, Ya-Xiong; Chang, Carlos C; Pipinos, Iraklis I; Goodchild, Traci T; Lefer, David J

    2015-07-01

    Nitrite is a storage reservoir of nitric oxide that is readily reduced to nitric oxide under pathological conditions. Previous studies have demonstrated that nitrite levels are significantly reduced in cardiovascular disease states, including peripheral vascular disease. We investigated the cytoprotective and proangiogenic actions of a novel, sustained-release formulation of nitrite (SR-nitrite) in a clinically relevant in vivo swine model of critical limb ischemia (CLI) involving central obesity and metabolic syndrome. CLI was induced in obese Ossabaw swine (n = 18) by unilateral external iliac artery deployment of a full cross-sectional vessel occlusion device positioned within an endovascular expanded polytetrafluoroethylene-lined nitinol stent-graft. At post-CLI day 14, pigs were randomized to placebo (n = 9) or SR-nitrite (80 mg, n = 9) twice daily by mouth for 21 days. SR-nitrite therapy increased nitrite, nitrate, and S-nitrosothiol in plasma and ischemic skeletal muscle. Oxidative stress was reduced in ischemic limb tissue of SR-nitrite- compared with placebo-treated pigs. Ischemic limb tissue levels of proangiogenic growth factors were increased following SR-nitrite therapy compared with placebo. Despite the increases in cytoprotective and angiogenic signals with SR-nitrite therapy, new arterial vessel formation and enhancement of blood flow to the ischemic limb were not different from placebo. Our data clearly demonstrate cytoprotective and proangiogenic signaling in ischemic tissues following SR-nitrite therapy in a very severe model of CLI. Further studies evaluating longer-duration nitrite therapy and/or additional nitrite dosing strategies are warranted to more fully evaluate the therapeutic potential of nitrite therapy in peripheral vascular disease. PMID:25910804

  13. Impact of Critical Limb Ischemia on Long-Term Cardiac Mortality in Diabetic Patients Undergoing Percutaneous Coronary Revascularization

    PubMed Central

    Liistro, Francesco; Angioli, Paolo; Grotti, Simone; Brandini, Rossella; Porto, Italo; Ricci, Lucia; Tacconi, Danilo; Ducci, Kenneth; Falsini, Giovanni; Bellandi, Guido; Bolognese, Leonardo

    2013-01-01

    OBJECTIVE Development of critical limb ischemia (CLI) has been reported as an independent predictor of cardiac mortality in diabetic patients. We aimed to determine whether CLI, managed in a structured setting of close collaboration between different vascular specialists and treated with early endovascular intervention, has any impact on long-term cardiac mortality of diabetic patients initially presenting with symptomatic coronary artery disease (CAD). RESEARCH DESIGN AND METHODS We designed a prospective observational study of 764 consecutive diabetic patients undergoing percutaneous coronary intervention (PCI) in whom development of CLI was assessed by a dedicated diabetic foot clinic. Cardiac mortality at 4-year follow-up was the primary end point of the study. RESULTS Among the 764 patients, 111 (14%) developed CLI (PCI-CLI group) and underwent revascularization of 145 limbs, with procedural success in 140 (96%). PCI-CLI patients at baseline had lower left ventricular ejection fraction (51 ± 11% vs. 53 ± 10%, P = 0.008), higher prevalence of dialysis (7% vs. 0.3%, P < 0.0001), and longer diabetes duration (13 ± 8 vs. 11 ± 7 years, P = 0.02) compared with PCI-only patients. At 4-year follow-up, cardiac mortality occurred in 10 (9%) PCI-CLI patients vs. 42 (6%) PCI-only patients (P = 0.2). Time-dependent Cox regression model for cardiac death revealed that CLI was not associated with an increased risk of cardiac mortality (hazard ratio 1.08 [95% CI 0.89–3.85]; P = 0.1). CONCLUSIONS The development of promptly assessed and aggressively treated CLI was not significantly associated with increased risk of long-term cardiac mortality in diabetic patients initially presenting with symptomatic CAD. PMID:23340882

  14. Therapeutic potential of sustained-release sodium nitrite for critical limb ischemia in the setting of metabolic syndrome

    PubMed Central

    Polhemus, David J.; Bradley, Jessica M.; Islam, Kazi N.; Brewster, Luke P.; Calvert, John W.; Tao, Ya-Xiong; Chang, Carlos C.; Pipinos, Iraklis I.; Goodchild, Traci T.

    2015-01-01

    Nitrite is a storage reservoir of nitric oxide that is readily reduced to nitric oxide under pathological conditions. Previous studies have demonstrated that nitrite levels are significantly reduced in cardiovascular disease states, including peripheral vascular disease. We investigated the cytoprotective and proangiogenic actions of a novel, sustained-release formulation of nitrite (SR-nitrite) in a clinically relevant in vivo swine model of critical limb ischemia (CLI) involving central obesity and metabolic syndrome. CLI was induced in obese Ossabaw swine (n = 18) by unilateral external iliac artery deployment of a full cross-sectional vessel occlusion device positioned within an endovascular expanded polytetrafluoroethylene-lined nitinol stent-graft. At post-CLI day 14, pigs were randomized to placebo (n = 9) or SR-nitrite (80 mg, n = 9) twice daily by mouth for 21 days. SR-nitrite therapy increased nitrite, nitrate, and S-nitrosothiol in plasma and ischemic skeletal muscle. Oxidative stress was reduced in ischemic limb tissue of SR-nitrite- compared with placebo-treated pigs. Ischemic limb tissue levels of proangiogenic growth factors were increased following SR-nitrite therapy compared with placebo. Despite the increases in cytoprotective and angiogenic signals with SR-nitrite therapy, new arterial vessel formation and enhancement of blood flow to the ischemic limb were not different from placebo. Our data clearly demonstrate cytoprotective and proangiogenic signaling in ischemic tissues following SR-nitrite therapy in a very severe model of CLI. Further studies evaluating longer-duration nitrite therapy and/or additional nitrite dosing strategies are warranted to more fully evaluate the therapeutic potential of nitrite therapy in peripheral vascular disease. PMID:25910804

  15. Penehyclidine hydrochloride postconditioning ameliorates cerebral ischemia-reperfusion injury: critical role of mitochondrial ATP sensitive potassium channel.

    PubMed

    Shu, Y; Li, Z; Han, B

    2016-01-01

    Cerebral ischemia/reperfusion (CI/R) leads to disability and death worldwide. However, limited approaches have been made in developing therapies to decrease the detrimental effects of CI/R. In the present study, we evaluated the effects of penehyclidine hydrochloride (PHC) postconditioning on CI/R injury and elucidated the underlying mechanisms. In CI/R rats, we showed that PHC postconditioning could effectively inhibit I/R-induced brain infarction and edema, and deficit of neurological function. In addition, PHC postconditioning significantly inhibited I/R-induced increase of proinflammatory cytokines and TUNEL-positive cell numbers. Moreover, the opening of mitochondrial permeability transition pore (mPTP) and oxidative stress resulting from I/R were suppressed notably by PHC postconditioning, as evidenced by increased absorbance at 540 nm in Ca2+-induced mitochondrial swelling test and increased SOD activity and decreased ROS and MDA level. 5-hydroxydecanoate (5-HD), a specific inhibitor of MitoKATP, was used to evaluate the role of MitoKATP in the neuroprotective effect of PHC postconditioning. The results showed that 5-HD could markedly suppress PHC postconditioning-caused inhibition of brain infarction and edema, deficit of neurological function, inflammation, apoptosis, opening of mPTP and oxidative stress induced by CI/R. The results demonstrated that PHC postconditioning could protect against I/R injury in brain through the inhibition of oxidative stress, mPTP opening, apoptosis and inflammation. Activation of MitoKATP was critical for PHC postconditioning-exhibited neuro-protective effects against I/R injury. These findings may provide a novel foundation for therapeutic strategies targeting cerebral protection against I/R damage. PMID:27049075

  16. Ghrelin Promotes Functional Angiogenesis in a Mouse Model of Critical Limb Ischemia Through Activation of Proangiogenic MicroRNAs.

    PubMed

    Katare, Rajesh; Rawal, Shruti; Munasinghe, Pujika Emani; Tsuchimochi, Hirotsugu; Inagaki, Tadakatsu; Fujii, Yutaka; Dixit, Parul; Umetani, Keiji; Kangawa, Kenji; Shirai, Mikiyasu; Schwenke, Daryl O

    2016-02-01

    Current therapeutic strategies for the treatment of critical limb ischemia (CLI) have only limited success. Recent in vitro evidence in the literature, using cell lines, proposes that the peptide hormone ghrelin may have angiogenic properties. In this study, we aim to investigate if ghrelin could promote postischemic angiogenesis in a mouse model of CLI and, further, identify the mechanistic pathway(s) that underpin ghrelin's proangiogenic properties. CLI was induced in male CD1 mice by femoral artery ligation. Animals were then randomized to receive either vehicle or acylated ghrelin (150 μg/kg sc) for 14 consecutive days. Subsequently, synchrotron radiation microangiography was used to assess hindlimb perfusion. Subsequent tissue samples were collected for molecular and histological analysis. Ghrelin treatment markedly improved limb perfusion by promoting the generation of new capillaries and arterioles (internal diameter less than 50 μm) within the ischemic hindlimb that were both structurally and functionally normal; evident by robust endothelium-dependent vasodilatory responses to acetylcholine. Molecular analysis revealed that ghrelin's angiogenic properties were linked to activation of prosurvival Akt/vascular endothelial growth factor/Bcl-2 signaling cascade, thus reducing the apoptotic cell death and subsequent fibrosis. Further, ghrelin treatment activated proangiogenic (miR-126 and miR-132) and antifibrotic (miR-30a) microRNAs (miRs) while inhibiting antiangiogenic (miR-92a and miR-206) miRs. Importantly, in vitro knockdown of key proangiogenic miRs (miR-126 and miR-132) inhibited the angiogenic potential of ghrelin. These results therefore suggest that clinical use of ghrelin for the early treatment of CLI may be a promising and potent inducer of reparative vascularization through modulation of key molecular factors. PMID:26672806

  17. Critical peripheral ischemia precipitated by severe episode of Raynaud's phenomenon in a patient with aPL-positive systemic lupus erythematosus, upon high titer anti-RNP seroconversion.

    PubMed

    Levy, O; Maslakov, I; Vosco, S; Markov, A; Amit-Vazina, M; Tishler, M

    2015-03-01

    A 35-year-old female with long standing aPL-positive lupus without history of thromboembolic events, who has developed critical peripheral ischemia (CPI) is described. An episode of severe Raynaud's phenomenon rapidly progressed to an extensive digit-threatening ischemia, involving bilateral hands and feet. She was successfully treated with corticosteroids, anticoagulation, iloprost, sildenafil, and nifedipine. Her serological studies were remarkable for the emergence of high titer anti-RNP seroconversion and an increase in aPL titer, suggesting that these autoantibodies played a role in the pathogenesis of CPI. It is important to note that such observation should herald this potentially devastating complication of systemic lupus erythematosus. PMID:25467391

  18. The mucus layer is critical in protecting against ischemia-reperfusion-mediated gut injury and in the restitution of gut barrier function.

    PubMed

    Qin, Xiaofa; Sheth, Sharvil U; Sharpe, Susan M; Dong, Wei; Lu, Qi; Xu, Dazhong; Deitch, Edwin A

    2011-03-01

    It is well documented that the gut injury plays a critical role in the development of systemic inflammation and distant organ injury in conditions associated with splanchnic ischemia. Consequently, understanding the mechanisms leading to gut injury is important. In this context, recent work suggests a protective role for the intestinal mucus layer and an injury-inducing role for luminal pancreatic proteases. Thus, we explored the role of the mucus layer in gut barrier function by observing how the removal of the mucus layer affects ischemia-reperfusion-mediated gut injury in rats as well as the potential role of luminal pancreatic proteases in the pathogenesis of gut injury. Ischemia was induced by the ligation of blood vessels to segments of the ileum for 45 min, followed by up to 3 h of reperfusion. The ileal segments were divided into five groups. These included a nonischemic control, ischemic segments exposed to saline, the mucolytic N-acetylcysteine (NAC), pancreatic proteases, or NAC + pancreatic proteases. Changes in gut barrier function were assessed by the permeation of fluorescein isothiocyanate dextran (molecular weight, 4,000 d) in ileal everted sacs. Gut injury was measured morphologically and by the luminal content of protein, DNA, and hemoglobin. The mucus layer was assessed functionally by measuring its hydrophobicity and morphologically. Gut barrier function was promptly and effectively reestablished during reperfusion, which was accompanied by the restoration of the mucus layer. In contrast, treatment of the gut with the mucolytic NAC for 10 min during ischemia resulted in a failure of mucus restitution and further increases in gut permeability and injury. The presence of digestive proteases by themselves did not exacerbate gut injury, but in combination with NAC, they caused an even greater increase in gut injury and permeability. These results suggest that the mucus layer not only serves as a barrier between the luminal contents and gut surface

  19. Hepatic ischemia

    MedlinePlus

    Hepatic ischemia is a condition in which the liver does not get enough blood or oxygen, causing injury to ... pressure from any condition can lead to hepatic ischemia. Such conditions may include: Abnormal heart rhythms Dehydration ...

  20. Critical Limb Ischemia (CLI)

    MedlinePlus

    ... or 911 immediately. @ 2016 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 555 Price Ave., Suite 180, Redwood City, ...

  1. Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia.

    PubMed

    Kumagai, Motoyuki; Marui, Akira; Tabata, Yasuhiko; Takeda, Takahide; Yamamoto, Masaya; Yonezawa, Atsushi; Tanaka, Shiro; Yanagi, Shigeki; Ito-Ihara, Toshiko; Ikeda, Takafumi; Murayama, Toshinori; Teramukai, Satoshi; Katsura, Toshiya; Matsubara, Kazuo; Kawakami, Koji; Yokode, Masayuki; Shimizu, Akira; Sakata, Ryuzo

    2016-05-01

    As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a 200-μg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI. PMID:25861983

  2. Adenoviral-mediated gene transfer of vascular endothelial growth factor in critical limb ischemia: safety results from a phase I trial.

    PubMed

    Mohler, Emile R; Rajagopalan, Sanjay; Olin, Jeffrey W; Trachtenberg, Jeffrey D; Rasmussen, Henrik; Pak, Raphael; Crystal, Ronald G

    2003-01-01

    Critical limb ischemia (CLI) is typified by rest pain and/or tissue necrosis secondary to advanced peripheral arterial disease (PAD) and is characterized by diminution in limb perfusion at rest. We tested the safety of an angiogenic strategy with CI-1023 (Ad(GV)VEGF121.10), a replication-deficient adenovirus encoding human vascular endothelial growth factor isoform 121 in patients with CLI as part of a phase I trial. Fifteen subjects >35 years of age with CLI and angiographic disease involving the infra-inguinal vessels underwent intramuscular injection of CI-1023 (4 x 10(8) to 4 x 10(10) particle units, n = 13) or placebo (n = 2). All of the patients tolerated the injection well and there were no serious complications related to the procedure. Transient edema was noted in one patient. A total of 79 adverse events were reported over the course of one year. One death (day 136) and one malignancy (day 332) occurred in the CI-1023 group. CI-1023 appears to be well tolerated and safe for single-dose administration in patients with critical limb ischemia due to PAD. Further studies are needed to determine the efficacy of this form of therapeutic angiogenesis. PMID:12866606

  3. Autologous Bone Marrow Mononuclear Cell Therapy is Safe and Promotes Amputation Free Survival in Patients with Critical Limb Ischemia

    PubMed Central

    Murphy, Michael P.; Lawson, Jeffrey H.; Rapp, Brian M.; Dalsing, Michael C.; Klein, Janet; Wilson, Michael G.; Hutchins, Gary D.; March, Keith L.

    2011-01-01

    Objective The purpose of this phase I open label non-randomized trial was to assess the safety and efficacy of autologous bone marrow mononuclear cell (ABMNC) therapy in promoting amputation free survival (AFS) in patients with critical limb ischemia (CLI). Methods Between September 2005 and March 2009 twenty-nine patients (30 limbs), with a median age of 66 (range 23–84) (14 male,15 female) with CLI were enrolled . Twentyone limbs presented with rest pain (RP), six with RP and ulceration, and three with ulcer only. All patients were not candidates for surgical bypass due to absence of a patent artery below the knee and/or endovascular approaches to improving perfusion was not possible as determined by an independent vascular surgeon. Patients were treated with an average dose of 1.7 ± 0.7 × 109 ABMNC injected intramuscularly in the index limb distal to the anterior tibial tuberosity. The primary safety endpoint was accumulation of serious adverse events and the primary efficacy endpoint was AFS at one year. Secondary endpoints at 12 weeks post-treatment were changes in first toe pressure (FTP), toe-brachial index (TBI), ankle-brachial index (ABI), and transcutaneous oxygen measurements (TcPO2). Perfusion of the index limb was measured with PET-CT with intra-arterial infusion of H2O15. Rest pain (RP), using a 10-cm visual analog scale, quality of life using the VascuQuol questionnaire, and ulcer healing were assessed at each follow-up interval. Subpopulations of endothelial progenitor cells were quantified prior to ABMNC administration using immunocytochemistry and fluorescent activated cell sorting. Results There were two serious adverse events however there no procedure related deaths. Amputation-free survival at one-year was 86.3%. There was a significant increase in FTP (10.2+ 6.2 mmHg, P=.02) and TBI (0.10± 0.05, P=.02) and a trend in improvement in ABI (0.08±0.04, P=.73). Perfusion Index by PET-CT H2O15 increased by 19.3 ± 3.1 and RP decreased

  4. The mucus layer is critical in protecting against ischemia/reperfusion-mediated gut injury and in the restitution of gut barrier function

    PubMed Central

    Qin, Xiaofa; Sheth, Sharvil U.; Sharpe, Susan M.; Dong, Wei; Lu, Qi; Xu, Dazhong; Deitch, Edwin A.

    2011-01-01

    It is well documented that the gut injury plays a critical role in the development of systemic inflammation and distant organ injury in conditions associated with splanchnic ischemia. Consequently understanding the mechanisms leading to gut injury is important. In this context, recent work suggests a protective role for the intestinal mucus layer and an injury-inducing role for luminal pancreatic proteases. Thus, we explored the role of the mucus layer in gut barrier function by observing how the removal of the mucus layer affects ischemia/reperfusion-mediated gut injury in rats as well as the potential role of luminal pancreatic proteases in the pathogenesis of gut injury. Ischemia was induced by the ligation of blood vessels to segments of the ileum for 45 min, followed by up to three hours of reperfusion. The ileal segments were divided into 5 groups. These included a non-ischemic control, ischemic segments exposed to saline, the mucolytic N-acetylcholine (NAC), pancreatic proteases or NAC plus pancreatic proteases. Changes in gut barrier function were assessed by the permeation of fluorescein isothiocyanate dextran (MW 4000 Da; FD4) in ileal everted sacs. Gut injury was measured morphologically and by the luminal content of protein, DNA and hemoglobin. The mucus layer was assessed functionally by measuring its hydrophobicity and morphologically. Gut barrier function was promptly and effectively re-established during reperfusion, which was accompanied by the restoration of the mucus layer. In contrast, treatment of the gut with the mucolytic NAC for 10 min during ischemia resulted in a failure of mucus restitution and further increases in gut permeability and injury. The presence of digestive proteases by themselves did not exacerbate gut injury but in combination with NAC, they caused an even greater increase in gut injury and permeability. These results suggest that the mucus layer not only serves as a barrier between the luminal contents and gut surface

  5. Different Mid-Term Prognostic Predictors of Major Adverse Events in Diabetic and Nondiabetic Peripheral Artery Disease Presenting With Critical Limb Ischemia.

    PubMed

    Liang, Kae-Woei; Kuo, Hsun-Nan; Lee, Wen-Lieng; Liu, Tsun-Jui; Lin, Wei-Wen; Tsao, Chen-Rong; Ting, Chih-Tai; Wang, Kuo-Yang

    2016-03-01

    We compared midterm prognostic predictors of peripheral artery disease (PAD) with or without diabetes mellitus (DM) presenting with critical lower limb ischemia (CLI). A total of 172 patients with PAD (109 DM; 63 non-DM) were enrolled. The major adverse events (MAEs) were death or amputation. The diabetic group had a higher MAE rate (39% vs 22%, P = .042) with a mean follow-up duration of 30 ± 19 months. In a multivariate binary logistic regression analysis, revascularization (odds ratio = 0.289, P = .006) and higher serum cholesterol (odds ratio=0.988, P = .027) predicted a lower MAE rate in the DM group. In contrast, the presence of severe chronic kidney disease (stage 4 or 5, odds ratio = 5.238, P = .025) was a positive predictor of MAEs in the nondiabetic group. In conclusion, the prognostic predictors of MAE in diabetic and nondiabetic patients with PAD and CLI were different. PMID:23389094

  6. Endovascular Therapy for Femoropopliteal Artery Disease and Association of Risk Factors With Primary Patency: The Implication of Critical Limb Ischemia and TASC II C/D Disease.

    PubMed

    Nishibe, Toshiya; Yamamoto, Kiyohito; Seike, Yoshimasa; Ogino, Hitoshi; Nishibe, Masayasu; Koizumi, Jun; Dardik, Alan

    2015-11-01

    The treatment of femoropopliteal artery disease remains controversial, without clear guidelines specifying the indications for endovascular therapy (EVT). Accordingly, we retrospectively examined our experience of using EVT to treat femoropopliteal artery disease. A total of 91 limbs in 82 patients underwent EVT for the treatment of femoropopliteal artery disease. Percutaneous transluminal angioplasty alone was performed in 20 limbs, and additional stenting was performed in 71 limbs. The 1-year primary patency, primary-assisted patency, limb salvage, and survival rates were 76%, 88%, 96%, and 92%, respectively. Multivariate Cox analysis of primary patency showed that critical limb ischemia (CLI; hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.08-5.33; P < .01) and TASC II C/D disease (HR, 2.70; 95% CI, 1.14-6.39; P < .05) were independent predictors of decreased primary patency. In conclusion, patients with CLI or extensive lesions have reduced patency after EVT for femoropopliteal artery disease. PMID:26574486

  7. Popliteal artery entrapment syndrome: a common cause of a rare clinical entity--critical leg ischemia in the young.

    PubMed

    Tsilogianni, Zoi; Grapatsas, Konstantinos; Papanikolaou, Zisis; Kokkini-Paschou, Aggeliki; Tsantilas, Apostolos; Tsiligiris, Vasileios; Vourliotakis, Georgios

    2014-01-01

    Popliteal artery entrapment syndrome (PAES) is a rare but important cause of leg ischemia and even disability in young athletes. Entrapment occurs because of an abnormal relationship between the popliteal artery and the surrounding muscular structures in the popliteal fossa. These anomalies lead to decreased blood flow to the affected leg with signs of claudication, coldness, and symptoms of exercise-induced leg pain. In this article, we present a case of a young soldier who presented with the above signs and symptoms in his left foot after exercise. On questioning, he admitted to having chronic lower leg pain. He was diagnosed with PAES in both legs and he was emergently treated with an arterial bypass procedure in the left one. He had no postoperative complications. PAES should be considered in the differential diagnosis of chronic or acute lower leg pain in any young patient. Early diagnosis and treatment can prevent limb loss and lead to a good operative outcome. PMID:24402998

  8. Clusterin/Akt Up-Regulation Is Critical for GATA-4 Mediated Cytoprotection of Mesenchymal Stem Cells against Ischemia Injury

    PubMed Central

    Yu, Bin; Yang, Yueting; Liu, Huan; Gong, Min; Millard, Ronald W.; Wang, Yi-Gang; Ashraf, Muhammad; Xu, Meifeng

    2016-01-01

    Background Clusterin (Clu) is a stress-responding protein with multiple biological functions. Our preliminary microarray studies show that clusterin was prominently upregulated in mesenchymal stem cells (MSCs) overexpressing GATA-4 (MSCGATA-4). We hypothesized that the upregulation of clusterin is involved in overexpression of GATA-4 mediated cytoprotection. Methods MSCs harvested from bone marrow of rats were transduced with GATA-4. The expression of clusterin in MSCs was further confirmed by real-time PCR and western blotting. Simulation of ischemia was achieved by exposure of MSCs to a hypoxic environment. Lactate dehydrogenase (LDH) released from MSCs was served as a biomarker of cell injury and MTs uptake was used to estimate cell viability. Mitochondrial function was evaluated by measuring mitochondrial membrane potential (ΔΨm) and caspase 3/7 activity. Results (1) Clusterin expression was up-regulated in MSCGATA-4 compared to control MSCs transfected with empty-vector (MSCNull). MSCGATA-4 were tolerant to 72 h hypoxia exposure as shown by reduced LDH release and higher MTs uptake. This protection was abrogated by transfecting Clu-siRNA into MSCGATA-4. (2) Exogenous clusterin significantly decreased LDH release and increased MSC survival in hypoxic environment. Moreover, ΔΨm was maintained and caspase 3/7 activity was reduced by clusterin in a concentration-dependent manner. (3) p-Akt expression in MSCs was upregulated following pre-treatment with clusterin, with no change in total Akt. Moreover, cytoprotection mediated by clusterin was partially abrogated by Akt inhibitor LY294002. Conclusions Clusterin/Akt signaling pathway is involved in GATA-4 mediated cytoprotection against hypoxia stress. It is suggested that clusterin may be therapeutically exploited in MSC based therapy for cardiovascular diseases. PMID:26962868

  9. Validation of the Society for Vascular Surgery’s Objective Performance Goals (OPGs) for Critical Limb Ischemia in Everyday Vascular Surgery Practice

    PubMed Central

    Goodney, Philip P.; Schanzer, Andres; DeMartino, Randall R.; Nolan, Brian W.; Hevelone, Nathanael D.; Conte, Michael S.; Powell, Richard J.; Cronenwett, Jack L.

    2010-01-01

    Background To develop standardized metrics for expected outcomes in lower extremity revascularization for critical limb ischemia (CLI), the SVS has developed objective performance goals (OPGs), based on aggregate data from randomized trials of lower extremity bypass. It remains unknown, however, if these targets can be achieved in everyday vascular surgery practice. Methods We applied SVS OPG criteria to 1,039 patients undergoing 1,039 lower extremity bypass operations (LEB) for CLI with autogenous vein (excluding dialysis patients) within the Vascular Study Group of New England (VSGNE). Each of the individual OPGs was calculated within the VSGNE dataset, along with its surrounding 95% confidence intervals, and compared to published SVS OPGs using chi squared comparisons and survival analysis. Results Across most risk strata, patients in the VSGNE and SVS OPG cohorts were similar (clinical high-risk [age>80 years and tissue loss]: 15.3% VSGNE, 16.2% SVS OPG, p=0.58; anatomic high risk [infrapopliteal target artery]: 57.8% VSGNE, 60.2% SVS OPG, p=0.32). However, the proportion of VSGNE patients designated as conduit high-risk (lack of single segment greater saphenous vein) was lower (10.2% VSGNE, 26.9% SVS OPG, p<0.001). The primary safety endpoint, major adverse limb event at 30 days (MALE), was lower in the VSGNE cohort (3.2%%, 95% CI 2.3–4.6%) than the SVS OPG cohort (6.2%, 95% CI 4.2–8.1) (p=0.05). The primary efficacy OPG endpoint, freedom from any major adverse limb event or post-operative death within the first year (MALE+POD), was similar between VSGNE and SVS OPG cohorts (77% (95% CI 74–80%) SVS OPG, 74% (95% CI 71–77%) VSGNE, p=0.58). In the remaining safety and efficacy OPGs, the VSGNE cohort met or exceeded the benchmarks established by the SVS OPG cohort. Conclusions Community and academic centers in everyday vascular surgery practice can meet OPGs derived from centers of excellence in LEB. Quality improvement initiatives, as well as clinical

  10. Nomograms used to define the short-term treatment with PGE(1) in patients with intermittent claudication and critical ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic Critical Limb) Study Group. The European Study.

    PubMed

    Belcaro, G; Nicolaides, A N; Cipollone, G; Laurora, G; Incandela, L; Cazaubon, M; Barsotti, A; Ledda, A; Errichi, B M; Cornelli, U; Dugall, M; Corsi, M; Mezzanotte, L; Geroulakos, G; Fisher, C; Szendro, G; Simeone, E; Cesarone, M R; Bucci, M; Agus, G; De Sanctis, M T; Ricci, A; Ippolito, E; Vasdekis, S; Christopoulos, D; Helmis, H

    2000-08-01

    Infusional, cyclic PGE1 treatment is effective in patients with intermittent claudication and critical limb ischemia (CLI). One of the problems related to chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate the variations of clinical conditions due to treatment in order to establish the number of cycles per year or per period (in severe vascular disease reevaluation of patients should be more frequent) needed to achieve clinical improvement. In a preliminary pilot study a group of 150 patients (mean age 67+/-12 years) with intermittent claudication (walking range from 0 to 500 m) and a group of 100 patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 +/-11 years) the number of PGE1 cycles according to the short-term protocol (STP) needed to produce significant clinical improvement was preliminarily evaluated. Considering these preliminary observations, the investigators established a research plan useful to produce nomograms indicating the number of cycles of PGE1-STP per year needed to improve the clinical condition (both in intermittent claudication and CLI). A significant clinical improvement was arbitrarily defined as the increase of at least 35% in walking distance (on treadmill) and/or the disappearance of signs and symptoms of critical ischemia in 6 months of treatment in at least 75% of the treated patients. With consideration of the results obtained with the preliminary nomograms a larger validation of the nomograms is now advisable. A cost-effectiveness analysis is also useful to define the efficacy of treatment on the basis of its costs. The publication of this report in two angiological journals (Angeiologie and Angiology) will open the research on nomograms to all centers willing to collaborate to the study. The data are being collected in the ORACL.E database and will be analyzed within 12 months after the publication of this report. PMID:10959506

  11. The BEST-CLI trial: a multidisciplinary effort to assess whether surgical or endovascular therapy is better for patients with critical limb ischemia.

    PubMed

    Menard, Matthew T; Farber, Alik

    2014-03-01

    Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease and is associated with a risk of limb loss. This vascular condition is currently treated with limb revascularization by surgery or endovascular intervention performed by a variety of specialists. Because both open vascular bypass and the less invasive endovascular therapy can be performed in selected patients with CLI, there exists significant disagreement as to which therapy should be performed first and which is more successful. The paucity of comparative effectiveness data to guide treatment of CLI has prompted a multidisciplinary effort to organize the Best Endovascular Versus Best Surgical Therapy in Patients With CLI (BEST-CLI) trial. The BEST-CLI trial is a pragmatic, multicenter, open-label, randomized trial that compares best endovascular therapy with best open surgical treatment in patients eligible for both treatments. BEST-CLI aims to provide urgently needed clinical guidance for CLI management by using a pragmatic design comparing the effectiveness of established techniques while allowing for the introduction of newer therapies as they become available; a novel primary endpoint that includes limb amputation rates, repeat intervention, and mortality; a multidisciplinary structure that fosters cooperation among interventional cardiologists, interventional radiologists, vascular surgeons, and vascular medicine specialists; and novel techniques to evaluate the cost-effectiveness and quality-of-life outcomes of the two treatment strategies being tested. PMID:25812762

  12. Cellular Therapy With Ixmyelocel-T to Treat Critical Limb Ischemia: The Randomized, Double-blind, Placebo-controlled RESTORE-CLI Trial

    PubMed Central

    Powell, Richard J; Marston, William A; Berceli, Scott A; Guzman, Raul; Henry, Timothy D; Longcore, Amy T; Stern, Theresa P; Watling, Sharon; Bartel, Ronnda L

    2012-01-01

    Ixmyelocel-T is a patient-specific, expanded, multicellular therapy evaluated in patients with lower extremity critical limb ischemia (CLI) with no options for revascularization. This randomized, double-blind, placebo-controlled, phase 2 trial (RESTORE-CLI) compared the efficacy and safety of intramuscular injections of ixmyelocel-T with placebo. Patients received one-time injections over 20 locations in a single leg and were followed for 12 months. Safety assessments included occurrence of adverse events. Efficacy assessments included time to first occurrence of treatment failure (TTF; major amputation of injected leg; all-cause mortality; doubling of total wound surface area from baseline; de novo gangrene) and amputation-free survival (AFS; major amputation of injected leg; all-cause mortality). A total of 77 patients underwent bone marrow or sham aspiration; 72 patients received ixmyelocel-T (48 patients) or placebo (24 patients). Adverse event rates were similar. Ixmyelocel-T treatment led to a significantly prolonged TTF (P = 0.0032, logrank test). AFS had a clinically meaningful 32% reduction in event rate that was not statistically significant (P = 0.3880, logrank test). Treatment effect in post hoc analyses of patients with baseline wounds was more pronounced (TTF: P < 0.0001, AFS: P = 0.0802, logrank test). Ixmyelocel-T treatment was well tolerated and may offer a potential new treatment option. PMID:22453769

  13. Improved quality of life in patients with no-option critical limb ischemia undergoing gene therapy with DVC1-0101

    PubMed Central

    Matsumoto, Takuya; Tanaka, Michiko; Yoshiya, Keiji; Yoshiga, Ryosuke; Matsubara, Yutaka; Horiuchi-Yoshida, Kumi; Yonemitsu, Yoshikazu; Maehara, Yoshihiko

    2016-01-01

    Critical limb ischemia (CLI) has a poor prognosis and adversely affects patients’ quality of life (QOL). Therapeutic angiogenesis may improve mobility, mortality, and QOL in CLI patients. However, the effectiveness of gene therapy on such patients’ QOL is unknown. DVC1-0101, a non-transmissible recombinant Sendai virus vector expressing human fibroblast growth factor-2 gene, demonstrated safety and efficacy in a phase I/II study of CLI patients. We investigated the effects of DVC1-0101 on QOL in this cohort. QOL was assessed using the Short Form-36 health survey version 2 (SF-36) in 12 patients at pre-administration, 28 days, and 3, 6, and 12 months post-treatment. We examined differences between pre and post-administration QOL scores and correlations between QOL scores and vascular parameters. Patients demonstrated low baselines scores on every SF-36 dimension. Post-treatment scores showed significant improvements in physical functioning at 3 and 6 months (P < 0.05), role-physical at 3, 6, and 12 months (P < 0.05), bodily pain at 1, 3, 6, and 12 months (P < 0.05), vitality at 1, 6, and 12 months (P < 0.05), and physical component summary at 6 and 12 months (P < 0.05). DVC1-0101-based gene therapy may improve QOL in CLI patients over a 6-month period. PMID:27418463

  14. Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: a phase I study.

    PubMed

    Henry, T D; Hirsch, A T; Goldman, J; Wang, Y L; Lips, D L; McMillan, W D; Duval, S; Biggs, T A; Keo, H H

    2011-08-01

    We aimed to evaluate in a phase I dose-escalation study, the safety of intramuscular injections of a novel non-viral plasmid DNA expressing two isoforms of human hepatocyte growth factor (HGF) (VM202) in patients with critical limb ischemia (CLI). In total, 12 patients with CLI and unsuitable for revascularization were consecutively assigned to increasing doses (2 to 16 mg) of VM202 administered into the ischemic calf muscle at days 1 and 15. Patients were evaluated for safety and tolerability, changes in ankle- and toe brachial index (ABI and TBI), and pain severity score using a visual analog scale (VAS) throughout a 12-month follow-up period. Median age was 72 years and 53% of the patients were male. VM202 was safe and well tolerated with no death during the 12-month follow-up. Median ABI and TBI significantly increased from 0.35 to 0.52 (P=0.005) and from 0.15 to 0.24 (P=0.01) at 12 months follow-up. Median VAS decreased from 57.5 to 16.0 mm at 6 months follow-up (P=0.03). In this first human clinical trial, VM202, which expresses two isoforms of human HGF, appear to be safe and well tolerated with encouraging clinical results and thus supports the performance of a phase II randomized controlled trial. PMID:21430785

  15. Effectiveness of Platelet-Rich Plasma to Enhance Healing of Diabetic Foot Ulcers in Patients With Concomitant Peripheral Arterial Disease and Critical Limb Ischemia.

    PubMed

    Kontopodis, Nikolaos; Tavlas, Emmanouhl; Papadopoulos, George; Pantidis, Dimitrios; Kafetzakis, Alexandros; Chalkiadakis, George; Ioannou, Christos

    2016-03-01

    We sought to investigate the effect of autologous platelet-rich plasma (PRP) on the healing rate of diabetic foot ulcers in patients with diabetes and concomitant peripheral arterial disease (PAD). Diabetic patients with foot ulceration presenting with PAD who were treated with local growth factors in a single center, during a 24-month period from May 2009 to April 2011, were retrospectively reviewed. Based on the severity of PAD, subjects were divided into groups A (Fontaine classification stages I, IIa, and IIb) and B (Fontaine classification stages III and IV), with those included in the latter being considered to suffer from critical limb ischemia (CLI). End points of the analysis were clinical improvement, limb salvage, and amputation rate. Outcome was compared between groups A and B. Overall, 72 patients were evaluated, 30 with CLI. Ulcer area reduction >50% was observed in 58/72 patients while reduction >90% was achieved in 52/72 patients. There were 14 (19%) major and minor amputations, whereas the limb salvage rate was 89%. This variable was significantly different between groups A and B (100% vs. 73%, P < .001), as is rate of reduction in ulcer area >90% (83% vs. 56%, P = .02). Reduction of ulcer area >50% was observed in the majority of patients in both groups (group A 86% vs. group B 73%, P = .23). In conclusion, PRP could serve as a useful adjunct during management of diabetic foot ulcers even in diabetic patients with unreconstructable arterial disease. PMID:25795280

  16. Early Results of Clinical Application of Autologous Whole Bone Marrow Stem Cell Transplantation for Critical Limb Ischemia with Buerger’s Disease

    PubMed Central

    Heo, Seon-Hee; Park, Yoong-Seok; Kang, Eun-Suk; Park, Kwang-Bo; Do, Young-Soo; Kang, Kyung-Sun; Kim, Dong-Ik

    2016-01-01

    Our goal was to evaluate early results of the clinical application of autologous whole bone marrow stem cell transplantation (AWBMSCT) for critical limb ischemia (CLI) in patients with Buerger’s disease. We retrospectively analyzed the data of 58 limbs of 37 patients (mean age, 43.0 years; range, 28–63 years; male, 91.9%) with Buerger’s disease with CLI who were treated with AWBMSCT from March 2013 to December 2014. We analyzed Rutherford category, pain score, pain-free walking time (PFWT), total walking time (TWT), ankle brachial pressure index (ABPI), and toe brachial pressure index (TBPI), and investigated wound healing and occurrence of unplanned amputations. The mean follow-up duration was 11.9 ± 7.2 months (range, 0.9–23.9 months) and 100%, 72.4%, and 74.1% of patients were available to follow-up 1, 3 and 6 months after AWBMST, respectively. At 6 months, patients demonstrated significant improvements in Rutherford category (P < 0.0001), pain score (P < 0.0001), PFWT (P < 0.0001) and TBPI (P < 0.0001). ABPI was increased compared to baseline, but the difference was not significant. A total of 76.5% ischemic wounds achieved complete or improved healing. AWBMSCT is a safe and effective alternative or adjunctive treatment modality to achieve clinical improvement in patients with CLI. PMID:26791280

  17. A Phase II Trial of Autologous Transplantation of Bone Marrow Stem Cells for Critical Limb Ischemia: Results of the Naples and Pietra Ligure Evaluation of Stem Cells Study

    PubMed Central

    Maione, Ciro; Botti, Chiara; Marino, Gennaro; Lillo, Stefano; Garrone, Alberto; Lanza, Lorella; Pagliari, Stefano; Silvestroni, Andrea; Signoriello, Giuseppe

    2012-01-01

    Critical limb ischemia (CLI) is a vascular disease affecting lower limbs, which is going to become a demanding challenge because of the aging of the population. Despite advances in endovascular therapies, CLI is associated with high morbidity and mortality. Patients without direct revascularization options have the worst outcomes. To date, 25%–40% of CLI patients are not candidates for surgical or endovascular approaches, ultimately facing the possibility of a major amputation. This study aimed to assess the safety and efficacy of autologous bone marrow (BM) transplantation performed in “no-option” patients, in terms of restoring blood perfusion by collateral flow and limb salvage. A multicenter, prospective, not-controlled phase II study for no-option CLI patients was performed. Patients were subjected to intra-arterial infusion of autologous bone marrow and followed for 12 months after the treatment. Variation of blood perfusion parameters, evaluated by laser Doppler flowmetry or transcutaneous oximetry, was set as the primary endpoint at 12 months after treatment and amputation-free survival as the secondary endpoint. Sixty patients were enrolled and treated with BM transplantation, showing improvement in objective and subjective measures of perfusion. Furthermore, survival analysis demonstrated improved amputation-free survival rates (75.2%) at 12 months after the treatment. This study provides further evidence that autologous bone marrow transplantation is well tolerated by CLI patients without adverse effects, demonstrating trends toward improvement in perfusion and reduced amputation rate, confirming the feasibility and safety of the procedure. PMID:23197862

  18. Improved quality of life in patients with no-option critical limb ischemia undergoing gene therapy with DVC1-0101.

    PubMed

    Matsumoto, Takuya; Tanaka, Michiko; Yoshiya, Keiji; Yoshiga, Ryosuke; Matsubara, Yutaka; Horiuchi-Yoshida, Kumi; Yonemitsu, Yoshikazu; Maehara, Yoshihiko

    2016-01-01

    Critical limb ischemia (CLI) has a poor prognosis and adversely affects patients' quality of life (QOL). Therapeutic angiogenesis may improve mobility, mortality, and QOL in CLI patients. However, the effectiveness of gene therapy on such patients' QOL is unknown. DVC1-0101, a non-transmissible recombinant Sendai virus vector expressing human fibroblast growth factor-2 gene, demonstrated safety and efficacy in a phase I/II study of CLI patients. We investigated the effects of DVC1-0101 on QOL in this cohort. QOL was assessed using the Short Form-36 health survey version 2 (SF-36) in 12 patients at pre-administration, 28 days, and 3, 6, and 12 months post-treatment. We examined differences between pre and post-administration QOL scores and correlations between QOL scores and vascular parameters. Patients demonstrated low baselines scores on every SF-36 dimension. Post-treatment scores showed significant improvements in physical functioning at 3 and 6 months (P < 0.05), role-physical at 3, 6, and 12 months (P < 0.05), bodily pain at 1, 3, 6, and 12 months (P < 0.05), vitality at 1, 6, and 12 months (P < 0.05), and physical component summary at 6 and 12 months (P < 0.05). DVC1-0101-based gene therapy may improve QOL in CLI patients over a 6-month period. PMID:27418463

  19. Preliminary Report of Endovascular Treatment for Critical Limb Ischemia Patients with Connective Tissue Disease: Cases Series and Review of the Literature.

    PubMed

    Obara, Hideaki; Matsubara, Kentaro; Fujimura, Naoki; Sekimoto, Yasuhito; Kitagawa, Yuko

    2015-06-01

    Only few studies have addressed the surgical revascularization in patients with both connective tissue disease (CTD) and critical limb ischemia (CLI), and the evidence for the endovascular treatment (EVT) is lacking in such patients. The main purpose of this study is to assess our outcome of EVT in patients with CTD and ischemic leg ulcers and review the current situation of the revascularization in such patients. Medical records of 10 consecutive patients with coexistent CTD and CLI-related leg ulcers (in 11 limbs) treated endovascularly at our institution between 2009 and 2013 were reviewed retrospectively. The patients had rheumatoid arthritis (n = 5), systemic lupus erythematosus (n = 1), progressive systemic scleroderma (n = 3), or polyarteritis nodosa (n = 1). EVT was technically successful in all the cases. No procedure-related morbidity or mortality occurred. During the mean follow-up period of 26 months, there were no major amputations, and sustained clinical improvement (ulcer healing and reduction in Rutherford category) was observed in eight limbs. The overall 1-year rates of amputation-free survival and freedom from reintervention were 89 and 81%, respectively. In our series of patients with CTD and ischemic leg ulcers, EVT had acceptable outcomes and may be recommended as a safe and reasonably effective initial treatment option for such patients. PMID:26060386

  20. Impact of deteriorated calcium-phosphate homeostasis on amputation-free survival after endovascular revascularization in patients with critical limb ischemia on hemodialysis.

    PubMed

    Hioki, Hirofumi; Miyashita, Yusuke; Shiraki, Tatsuya; Iida, Osamu; Uematsu, Masaaki; Miura, Takashi; Ebisawa, Souichirou; Ikeda, Uichi

    2016-04-01

    Patients on hemodialysis (HD) have abnormalities of calcium-phosphate (CaP) homeostasis and high CaP product contributes to atherosclerosis pathogenesis and adverse events. Patients on HD with critical limb ischemia (CLI) are at risk for major amputation and death because of advanced systemic atherosclerotic disease. The aim of this study was to evaluate the relationship between CaP product and amputation-free survival (AFS) in CLI after endovascular treatment (EVT). We retrospectively analyzed 221 CLI patients on HD. In Kaplan-Meier analysis, AFS was significantly lower in patients with CaP product ⩾ 55 mg(2)/dL(2) compared to those with CaP product <55 mg(2)/dL(2) (54.3% vs 78.5%, p = 0.002). However, neither serum phosphate nor calcium levels were individually associated with AFS. In multivariate analysis, CaP product ⩾ 55 mg(2)/dL(2) was an independent predictor for AFS in CLI patients on HD (hazard ratio, 3.03; 95% confidence interval, 1.78-5.15; p-value < 0.001). We concluded abnormal CaP homeostasis was associated with lower AFS after EVT in CLI patients on HD, and can serve for their risk stratification. PMID:26681436

  1. Patient skin dose measurements using a cable free system MOSFETs based in fluoroscopically guided percutaneous vertebroplasty, percutaneous disc decompression, radiofrequency medial branch neurolysis, and endovascular critical limb ischemia.

    PubMed

    Falco, Maria D; Masala, Salvatore; Stefanini, Matteo; Fiori, Roberto; Gandini, Roberto; Bagalà, Paolo; Morosetti, Daniele; Calabria, Eros; Tonnetti, Alessia; Verona-Rinati, Gianluca; Santoni, Riccardo; Simonetti, Giovanni

    2015-01-01

    The purpose of this work has been to dosimetrically investigate four fluoroscopically guided interventions: the percutaneous vertebroplasty (PVP), the percutaneous disc decompression (PDD), the radiofrequency medial branch neurolysis (RF) (hereafter named spine procedures), and the endovascular treatment for the critical limb ischemia (CLI). The X-ray equipment used was a Philips Integris Allura Xper FD20 imaging system provided with a dose-area product (DAP) meter. The parameters investigated were: maximum skin dose (MSD), air kerma (Ka,r), DAP, and fluoroscopy time (FT). In order to measure the maximum skin dose, we employed a system based on MOSFET detectors. Before using the system on patients, a calibration factor Fc and correction factors for energy (CkV) and field size (CFD) dependence were determined. Ka,r, DAP, and FT were extrapolated from the X-ray equipment. The analysis was carried out on 40 patients, 10 for each procedure. The average fluoroscopy time and DAP values were compared with the reference levels (RLs) proposed in literature. Finally, the correlations between MSD, FT, Ka,r, and DAP values, as well as between DAP and FT values, were studied in terms of Pearson's product-moment coefficients for spine procedures only. An Fc value of 0.20 and a very low dependence of CFD on field size were found. A third-order polynomial function was chosen for CkV. The mean values of MSD ranged from 2.3 to 10.8cGy for CLI and PVP, respectively. For these procedures, the DAP and FT values were within the proposed RL values. The statistical analysis showed little correlation between the investigated parameters. The interventional procedures investigated were found to be both safe with regard to deterministic effects and optimized for stochastic ones. In the spine procedures, the observed correlations indicated that the estimation of MSD from Ka,r or DAP was not accurate and a direct measure of MSD is therefore recommended. PMID:25679159

  2. Hydrogen Sulfide Levels and Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) Activity Are Attenuated in the Setting of Critical Limb Ischemia (CLI)

    PubMed Central

    Islam, Kazi N; Polhemus, David J; Donnarumma, Erminia; Brewster, Luke P; Lefer, David J

    2015-01-01

    Background Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are endogenous enzymatic sources of hydrogen sulfide (H2S). Functions of H2S are mediated by several targets including ion channels and signaling proteins. Nuclear factor-erythroid 2-related factor 2 is responsible for the expression of antioxidant response element–regulated genes and is known to be upregulated by H2S. We examined the levels of H2S, H2S-producing enzymes, and nuclear factor-erythroid 2-related factor 2 activation status in skeletal muscle obtained from critical limb ischemia (CLI) patients. Methods and Results Gastrocnemius tissues were attained postamputation from human CLI and healthy control patients. We found mRNA and protein levels of cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase were significantly decreased in skeletal muscle of CLI patients as compared to control. H2S and sulfane sulfur levels were significantly decreased in skeletal muscle of CLI patients. We also observed significant reductions in nuclear factor-erythroid 2-related factor 2 activation as well as antioxidant proteins, such as Cu, Zn-superoxide dismutase, catalase, and glutathione peroxidase in skeletal muscle of CLI patients. Biomarkers of oxidative stress, such as malondialdehyde and protein carbonyl formation, were significantly increased in skeletal muscle of CLI patients as compared to healthy controls. Conclusions The data demonstrate that H2S bioavailability and nuclear factor-erythroid 2-related factor 2 activation are both attenuated in CLI tissues concomitant with significantly increased oxidative stress. Reductions in the activity of H2S-producing enzymes may contribute to the pathogenesis of CLI. PMID:25977470

  3. Bilateral Administration of Autologous CD133+ Cells in Ambulatory Patients with Refractory Critical Limb Ischemia: Lessons Learned from a Pilot Randomized, Double blind, Placebo-controlled Trial

    PubMed Central

    Raval, Amish N.; Schmuck, Eric; Tefera, Girma; Leitzke, Cathlyn; Ark, Cassondra Vander; Hei, Derek; Centanni, John M.; de Silva, Ranil; Koch, Jill; Chappell, Richard; Hematti, Peiman

    2014-01-01

    Introduction CD133+ cells confer angiogenic potential and may be beneficial for the treatment of critical limb ischemia (CLI). However, patient selection, blinding methods and endpoints for clinical trials is challenging. We hypothesized that bilateral intramuscular administration of cytokine mobilized CD133+ cells in ambulatory patients with refractory CLI would be feasible and safe. Methods In this double-blind, randomized, sham-controlled trial, subjects received subcutaneous injections of granulocyte colony stimulating factor (10 mcg/kg/d) for 5 days, followed by leukapheresis, and intramuscular administration of 50-400 million sorted CD133+ cells delivered into both legs. Control subjects received normal saline injections, sham leukapheresis and intramuscular injection of placebo buffered solution. Subjects were followed for 1 year. An aliquot of CD133+ cells was collected from each subject to test for genes associated with cell senescence. Results 70 subjects were screened, of whom 10 were eligible. Subject enrollment was suspended due to a high rate of mobilization failure in subjects randomized to treatment. Of 10 subjects enrolled (7 randomized to treatment, 3 randomized to control), there were no differences in serious adverse events at 12 months and blinding was preserved. There were non-significant trends toward improved amputation free survival, 6 minute walk distance, walking impairment questionnaire and quality of life in subjects randomized to treatment. Successful CD133+ mobilizers expressed fewer senescence associated genes compared to poor mobilizers. Conclusion Bilateral administration of autologous CD133+ cell in ambulatory CLI subjects was safe and blinding was preserved. However, poor mobilization efficiency combined with high CD133+ senescence suggests futility in this approach. PMID:25239491

  4. Superiority of Transcutaneous Oxygen Tension Measurements in Predicting Limb Salvage After Below-the-Knee Angioplasty: A Prospective Trial in Diabetic Patients With Critical Limb Ischemia

    SciTech Connect

    Redlich, Ulf; Xiong, Yan Y.; Pech, Maciej; Tautenhahn, Joerg; Halloul, Zuhir; Lobmann, Ralf; Adolf, Daniela; Ricke, Jens; Dudeck, Oliver

    2011-04-15

    Purpose: To assess postprocedural angiograms, the ankle-brachial index (ABI), and transcutaneous oxygen tension (TcPO{sub 2}) to predict outcome after infrageniculate angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI) scheduled for amputation. Materials and Methods: PTA was performed in 28 diabetic patients with CLI confined to infrapopliteal vessels. We recorded patency of crural vessels, including the vascular supply of the foot as well as the ABI and TcPO{sub 2} of the foot. Results: Technical success rate was 92.9% (n = 26), and limb-salvage rate at 12 months was 60.7% (n = 17). The number of patent straight vessels above and below the level of the malleoli increased significantly in patients avoiding amputation. Amputation was unnecessary in 88.2% (n = 15) patients when patency of at least one tibial artery was achieved. In 72.7% (n = 8) of patients, patency of the peroneal artery alone was not sufficient for limb salvage. ABI was of no predictive value for limb salvage. TcPO{sub 2} values increased significantly only in patients not requiring amputation (P = 0.015). In patients with only one tibial artery supplying the foot or only a patent peroneal artery in postprocedural angiograms, TcPO{sub 2} was capable of reliably predicting the outcome. Conclusion: Below-the-knee PTA as an isolated part of therapy was effective to prevent major amputation in more than a half of diabetic patients with CLI. TcPO{sub 2} was a valid predictor for limb salvage, even when angiographic outcome criteria failed.

  5. IN.PACT Amphirion paclitaxel eluting balloon versus standard percutaneous transluminal angioplasty for infrapopliteal revascularization of critical limb ischemia: rationale and protocol for an ongoing randomized controlled trial

    PubMed Central

    2014-01-01

    Background The effectiveness and durability of endovascular revascularization therapies for chronic critical limb ischemia (CLI) are challenged by the extensive burden of infrapopliteal arterial disease and lesion-related characteristics (e.g., severe calcification, chronic total occlusions), which frequently result in poor clinical outcomes. While infrapopliteal vessel patency directly affects pain relief and wound healing, sustained patency and extravascular care both contribute to the ultimate “patient-centric” outcomes of functional limb preservation, mobility and quality of life (QoL). Methods/Design IN.PACT DEEP is a 2:1 randomized controlled trial designed to assess the efficacy and safety of infrapopliteal arterial revascularization between the IN.PACT Amphirion™ paclitaxel drug-eluting balloon (IA-DEB) and standard balloon angioplasty (PTA) in patients with Rutherford Class 4-5-6 CLI. Discussion This multicenter trial has enrolled 358 patients at 13 European centers with independent angiographic core lab adjudication of the primary efficacy endpoint of target lesion late luminal loss (LLL) and clinically driven target lesion revascularization (TLR) in major amputation-free surviving patients through 12-months. An independent wound core lab will evaluate all ischemic wounds to assess the extent of healing and time to healing at 1, 6, and 12 months. A QoL questionnaire including a pain scale will assess changes from baseline scores through 12 months. A Clinical Events Committee and Data Safety Monitoring Board will adjudicate the composite primary safety endpoints of all-cause death, major amputation, and clinically driven TLR at 6 months and other trial endpoints and supervise patient safety throughout the study. All patients will be followed for 5 years. A literature review is presented of the current status of endovascular treatment of CLI with drug-eluting balloon and standard PTA. The rationale and design of the IN.PACT DEEP Trial are

  6. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia

    PubMed Central

    2013-01-01

    Background Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI. Methods Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment – related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb. Results Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells. Conclusion BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies. Trial registration NIH website (http

  7. Prospective multicenter study of quality of life before and after lower extremity vein bypass in 1404 patients with critical limb ischemia

    PubMed Central

    Nguyen, Louis L.; Moneta, Gregory L.; Conte, Michael S.; Bandyk, Dennis F.; Clowes, Alexander W.; Seely, B. Lynn

    2010-01-01

    Background Patients with critical limb ischemia (CLI) have multiple comorbidities and limited life spans. The ability of infrainguinal vein bypass to improve quality of life (QoL) in patients with CLI has therefore been questioned. Prospective preoperative and postoperative QoL data for patients undergoing lower extremity vein bypass for CLI are presented. Methods A validated, disease-specific QoL questionnaire (VascuQoL) with activity, symptom, pain, emotional, and social domains and responses scored 1 (lowest QoL) to 7 (best QoL) was administered before surgery and at 3 and 12 months after lower extremity vein bypass for CLI. Changes in QoL at 3 and 12 months after lower extremity vein bypass and multiple predetermined variables potentially influencing QoL after lower extremity vein bypass were analyzed to determine the effect of lower extremity vein bypass on QoL in CLI patients. Results A total of 1404 patients had lower extremity vein bypass for CLI at 83 centers in the United States and Canada as part of the PREVENT III clinical trial. Surveys were completed in 1296 patients at baseline, 862 patients at 3 months, and 732 patients at 12 months. The global QoL score (mean ± SD) was 2.8 ± 1.1 at baseline and was 4.7 ± 1.4 and 5.1 ± 1.4 at 3 and 12 months, respectively. Mean changes from baseline at 3 and 12 months were statistically significant (P < .0001). Improved QoL scores extended across all domains. Diabetes and the development of graft-related events were associated with decreased improvement in QoL scores, though the mean relative change from baseline remained positive. Conclusions Patients with CLI have a low QoL at baseline that is improved at 3 and 12 months after lower extremity vein bypass. QoL improvements are lower in diabetic patients and those who develop graft-related events. Successful revascularization can be expected to improve QoL in patients with CLI, with benefits that are sustained to at least 1 year. PMID:17098529

  8. Female gender and oral anticoagulants are associated with wound complications in lower extremity vein bypass: An analysis of 1404 operations for critical limb ischemia

    PubMed Central

    Nguyen, Louis L.; Brahmanandam, Soma; Bandyk, Dennis F.; Belkin, Michael; Clowes, Alexander W.; Moneta, Gregory L.; Conte, Michael S.

    2010-01-01

    Background Infrainguinal bypass (IB) surgery is an effective means of improving arterial circulation to the lower extremity for patients with critical limb ischemia (CLI). However, wound complications (WC) of the surgical incision following IB can impart significant morbidity. Methods A retrospective analysis of WC from the 1404 patients enrolled in a multicenter clinical trial of vein bypass grafting for CLI was performed. Univariate and multivariable regression models were used to determine WC predictors and associated outcomes, including graft patency, limb salvage, quality of life (QoL), resource utilization (RU), and mortality. Results A total of 543 (39%) patients developed a reported WC within 30 days of surgery, with infections (284, 52%) and hematoma/hemorrhage (121, 22%) being the most common type. Postoperative anticoagulation (odds ratio [OR], 1.554; 95% confidence interval [CI] 1.202 to 2.009; P = .0008) and female gender (OR, 1.376; 95% CI, 1.076 to 1.757; P = .0108) were independent factors associated with WC. Primary, primary-assisted, and secondary graft patency rates were not influenced by the presence of WC; though, patients with WC were at increased risk for limb loss (hazard ratio [HR], 1.511; 95% CI 1.096 to 2.079; P = .0116) and higher mortality (HR, 1.449; 95% CI 1.098 to 1.912; P = .0089). WC was not significantly associated with lower QoL at 3 months (4.67 vs 4.79, P = .1947) and 12 months (5.02 vs 5.13, P = .2806). However, the subset of patients with serious WC (SWC) demonstrated significantly lower QoL at 3 months compared with patients without WC, (4.43 vs 4.79, respectively, P = .0166), though this difference was not seen at 12 months (4.94 vs 5.13, P = .2411). Patients with WC had higher RU than patients who did not have WC. Mean index length of hospital stay (LOS) was 2.3 days longer, mean cumulative 1-year LOS was 8.1 days longer, and mean number of hospitalizations was 0.5 occurrences greater for patients with WC compared with

  9. The AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients.

    PubMed

    Rief, Peter; Pichler, Martin; Raggam, Reinhard; Hafner, Franz; Gerger, Armin; Eller, Philipp; Brodmann, Marianne; Gary, Thomas

    2016-06-01

    The aspartat aminotransferase (AST)/alanin aminotransferase (ALT) (De-Ritis) ratio (AAR) is an easily applicable blood test. An elevated AAR on the one hand has been associated with an increase in nonalcoholic fatty liver disease (NAFLD). NAFLD on the other hand is associated with an increase in cardiovascular disease, all-cause mortality, and diabetes. As the AAR is also elevated in case of muscular damage, we investigated AAR and its association with critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients.In our cross-sectional study, we included 1782 PAOD patients treated at our institution from 2005 to 2010. Patients with chronic alcohol consumption (>20 g/day) were excluded. AAR was calculated and the cohort was categorized into tertiles according to the AAR. An optimal cut-off value for the continuous AAR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI.In our cohort, occurrence of CLI significantly increased with an elevation in AAR. As an optimal cut-off value, an AAR of 1.67 (sensitivity 34.1%, specificity 81.0%) was identified. Two groups were categorized, 1st group containing 1385 patients (AAR < 1.67) and a 2nd group with 397 patients (AAR > 1.67). CLI was more frequent in AAR > 1.67 patients (166 [41.9%]) compared to AAR < 1.67 patients (329 [23.8%]) (P < 0.001), as was prior myocardial infarction (28 [7.1%] vs 54 [3.9%], P = 0.01). Regarding inflammatory parameters, C-reactive protein (median 8.1 mg/L [2.9-28.23] vs median 4.3 mg/L [2.0-11.5]) and fibrinogen (median 427.5 mg/dL [344.25-530.0] vs 388.0 mg/dL [327.0-493.0]) also significantly differed in the 2 patient groups (both P < 0.001). Finally, an AAR > 1.67 was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] 1.7-2.3) for CLI even after adjustment for other well-established vascular risk factors.An increased AAR is significantly associated with patients

  10. Rodent models of cerebral ischemia

    SciTech Connect

    Ginsberg, M.D.; Busto, R. )

    1989-12-01

    The use of physiologically regulated, reproducible animal models is crucial to the study of ischemic brain injury--both the mechanisms governing its occurrence and potential therapeutic strategies. Several laboratory rodent species (notably rats and gerbils), which are readily available at relatively low cost, are highly suitable for the investigation of cerebral ischemia and have been widely employed for this purpose. We critically examine and summarize several rodent models of transient global ischemia, resulting in selective neuronal injury within vulnerable brain regions, and focal ischemia, typically giving rise to localized brain infarction. We explore the utility of individual models and emphasize the necessity for meticulous experimental control of those variables that modulate the severity of ischemic brain injury.169 references.

  11. Strategy of Revascularization for Critical Limb Ischemia Due to Infragenicular Lesions—Which Should Be Selected Firstly, Bypass Surgery or Endovascular Therapy?

    PubMed Central

    Iwasa, Kazuomi; Yamaoka, Terutoshi

    2015-01-01

    Background and Objectives: In patients with peripheral arterial diseases (PADs) due to infra-popliteal (below the knee; BTK) lesions, we often encounter situations requiring the immediate selection of either of two revascularization methods, namely bypass surgery or endovascular therapy (EVT). However, the question of whether endovascular or surgical revascularization should be performed initially for critical limb ischemia (CLI) patients with BTK lesions has not been clarified. To assess the efficacy and durability of EVT or bypass as a first approach, we evaluated the short- and mid-term outcomes of the first revascularizations achieved using EVT (EVT First Group; EVT-first) compared with bypass (Bypass First Group; Bypass-first). To verify the validity of each initial revascularization, we explored factors influencing overall survival (OS) rates using multivariate analyses. Methods: A total of 169 consecutive BTK revascularization procedures (150 patients) for CLI conducted at our facility between November 2006 and July 2012 were analyzed. Patients undergoing revascularization were divided into two groups (EVT-first or Bypass-first), with 102 patients undergoing endovascular therapy first (EVT-first) and 51 undergoing bypass surgery first (Bypass-first). No statistically significant differences were noted between the two groups with respect to preoperative background including age, gender, and cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, coronary arterial disease (CAD), chronic heart failure (CHF), cerebrovascular disease, and hemodialysis). Technical success was defined as a single straight-line flow to the ankle after completion angiography of the first revascularization method. Hemodynamic success was defined as a postoperative skin perfusion pressure of the foot exceeding 40 mmHg. Results: The average age of patients was 76.0 years (range, 46–98 years; 65 men and 37 women) and 72.3 years (range, 43–93 years; 35 men and 13 women

  12. Mesenteric artery ischemia

    MedlinePlus

    ... ischemia is often seen in people who have hardening of the arteries in other parts of the ... long-term (chronic) mesenteric artery ischemia caused by hardening of the arteries ( atherosclerosis ): Abdominal pain after eating ...

  13. [Imaging of intestinal ischemia].

    PubMed

    Van Beers, B E; Danse, E; Hammer, F; Goffette, P

    2004-04-01

    Ischemic bowel disease includes acute and chronic mesenteric ischemia, and colon ischemia. Cross-sectional imaging, and more particularly computed tomography, has an increasing role in the detection of acute and chronic mesenteric ischemia. Vascular obstructions or stenoses and changes in the bowel wall can be observed. Functional information can be added with MRI by using sequences that are sensitive to oxygen saturation in the superior mesenteric vein. Arteriography remains the reference examination in patients with acute mesenteric ischemia. PMID:15184799

  14. Role of Endothelial Cells in Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Singhal, Arun K.; Symons, J. David; Boudina, Sihem; Jaishy, Bharat; Shiu, Yan-Ting

    2014-01-01

    Minimizing myocardial ischemia-reperfusion injury has broad clinical implications and is a critical mediator of cardiac surgical outcomes. “Ischemic injury” results from a restriction in blood supply leading to a mismatch between oxygen supply and demand of a sufficient intensity and/or duration that leads to cell necrosis, whereas ischemia-reperfusion injury occurs when blood supply is restored after a period of ischemia and is usually associated with apoptosis (i.e. programmed cell death). Compared to vascular endothelial cells, cardiac myocytes are more sensitive to ischemic injury and have received the most attention in preventing myocardial ischemia-reperfusion injury. Many comprehensive reviews exist on various aspects of myocardial ischemia-reperfusion injury. The purpose of this review is to examine the role of vascular endothelial cells in myocardial ischemia-reperfusion injury, and to stimulate further research in this exciting and clinically relevant area. Two specific areas that are addressed include: 1) data suggesting that coronary endothelial cells are critical mediators of myocardial dysfunction after ischemia-reperfusion injury; and 2) the involvement of the mitochondrial permeability transition pore in endothelial cell death as a result of an ischemia-reperfusion insult. Elucidating the cellular signaling pathway(s) that leads to endothelial cell injury and/or death in response to ischemia-reperfusion is a key component to developing clinically applicable strategies that might minimize myocardial ischemia-reperfusion injury. PMID:25558187

  15. Monitored extended secondary arterial ischemia in a free muscle transfer.

    PubMed

    Sværdborg, Mille; Birke-Sørensen, Hanne

    2012-02-01

    In reconstructive microsurgery, flap failure can be catastrophic to the patient. Different monitoring methods have been implemented in an attempt to recognize secondary ischemia during its early stages. However, the exact onset of secondary ischemia can be difficult to determine because there are no well-documented and reliable monitoring techniques that offer true continuous monitoring in a clinical setting. Because of the uncertain time in terms of the onset of secondary ischemia, the exact length of ischemia before revascularization, the secondary ischemia time, cannot be obtained. This is probably part of the reason why not much has been published regarding the effect of secondary ischemia time in reference to flap survival. We present a case of a free gracilis muscle flap that was salvaged despite more than 11 hours of arterial ischemia. The flap was monitored using microdialysis and at no time was the ischemia clearly demonstrated by clinical inspection. We conclude that clinical monitoring in some cases can be an unreliable method for monitoring free muscle transfers suffering from arterial ischemia and that further studies are needed for more specific guidelines regarding the critical secondary ischemia time in muscle flaps. PMID:21959552

  16. Retrograde Approach Using Surgical Cutdown Technique for Limb Salvage in a Case of Critical Limb Ischemia With Severely Calcified Tibial Occlusive Disease.

    PubMed

    Shiraki, Tatsuya; Iida, Osamu; Suemitsu, Kotaro; Tsuji, Yoriko; Uematsu, Masaaki

    2016-05-01

    We here report a successful angioplasty for tibial artery occlusion using direct tibial puncture and subsequent retrograde approach under surgical cutdown technique. An 82-year-old man with ulcer/gangrene in first and second digits was referred to our hospital for endovascular therapy (EVT) of lower extremity ischemia. Diagnostic angiogram revealed anterior tibial artery (ATA) occlusion with severe calcification. Subintimal angioplasty was attempted using a 0.014-inch hydrophilic guidewire but was unsuccessful. A retrograde approach was subsequently attempted for ATA recanalization. However, because of severe calcification of dorsal pedis artery (DPA), percutaneous distal puncture was also unsuccessful. Direct puncture under surgical cutdown technique for DPA was subsequently performed and was successful. A 0.014-inch hydrophilic wire was advanced in retrograde fashion across the ATA occlusion and was used to access the microcatheter positioned at the proximal ATA via antegrade approach. Angioplasty of the ATA occlusion was performed using a 2.5-/3.0-mm tapered balloon. Completion angiogram revealed restoration of flow without dissection. Skin perfusion pressure was dramatically improved. Complete wound healing was achieved 5 months after EVT. PMID:27207678

  17. Inhibitor of DNA Binding 1 Is Induced during Kidney Ischemia-Reperfusion and Is Critical for the Induction of Hypoxia-Inducible Factor-1α

    PubMed Central

    Wen, Dan; Zou, Yan-Fang; Gao, Yao-Hui; Zhao, Qian; Xie, Yin-Yin; Shen, Ping-Yan; Xu, Yao-Wen; Xu, Jing; Chen, Yong-Xi; Feng, Xiao-Bei; Shi, Hao; Zhang, Wen

    2016-01-01

    In this study, rat models of acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) and HK-2 cell models of hypoxia-reoxygenation (H/R) were established to investigate the expression of inhibitor of DNA binding 1 (ID1) in AKI, and the regulation relationship between ID1 and hypoxia-inducible factor 1 alpha (HIF-1α). Through western blot, quantitative real-time PCR, immunohistochemistry, and other experiment methods, the induction of ID1 after renal I/R in vivo was observed, which was expressed mainly in renal tubular epithelial cells (TECs). ID1 expression was upregulated in in vitro H/R models at both the protein and mRNA levels. Via RNAi, it was found that ID1 induction was inhibited with silencing of HIF-1α. Moreover, the suppression of ID1 mRNA expression could lead to decreased expression and transcription of HIF-1α during hypoxia and reoxygenation. In addition, it was demonstrated that both ID1 and HIF-1α can regulate the transcription of twist. This study demonstrated that ID1 is induced in renal TECs during I/R and can regulate the transcription and expression of HIF-1α. PMID:27127787

  18. Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy

    PubMed Central

    2014-01-01

    Objective We tested the hypothesis that clopidogrel and cilostazol combination therapy could effectively attenuate systemic inflammatory reaction, facilitate proliferation of circulating endothelial progenitor cell (EPC), and improve the clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for surgical revascularization or percutaneous transluminal angioplasty (PTA). Methods A total 55 patients (mean age, 72 years; 56% female) were consecutively enrolled. Clopidogrel and cilostazol combination therapy was administered throughout the study period. Results As compared with the baseline, circulating endothelial progenitor cell level (as shown by flow cytometry) was significantly increased (p < 0.003), whereas the CLI-related ulcers and painfulness were significantly improved (all p < 0.01) by day 90 after treatment. On the other hand, after clopidogrel and cilostazol combination therapy, galectin-3 level, lipoprotein-associated phospholipase A2 gene expression, and RhoA/ROCK-related protein expression in peripheral blood mononuclear cells were significantly suppressed (all p < 0.01). Eventually, by day 90, 5 patients (9.1%) died of other etiologies, 3 (5.5%) withdrew from the study, 6 (10.9%) required amputation, and the remaining 41 had satisfactory clinical improvement with complete wound healing in 9 (16.4%) patients. Conclusion The results of the present study highlight that clopidogrel and cilostazol combination therapy may be considered to be an alternative method for treating patients with CLI unsuitable for surgical revascularization or PTA. PMID:24742198

  19. Neuroprotection after cerebral ischemia

    PubMed Central

    Namura, Shobu; Ooboshi, Hiroaki; Liu, Jialing; Yenari, Midori A.

    2013-01-01

    Cerebral ischemia, a focal or global insufficiency of blood flow to the brain, can arise through multiple mechanisms, including thrombosis and arterial hemorrhage. Ischemia is a major driver of stroke, one of the leading causes of morbidity and mortality worldwide. While the general etiology of cerebral ischemia and stroke has been known for some time, the conditions have only recently been considered treatable. This report describes current research in this field seeking to fully understand the pathomechanisms underlying stroke; to characterize the brain’s intrinsic injury, survival, and repair mechanisms; to identify putative drug targets as well as cell-based therapies; and to optimize the delivery of therapeutic agents to the damaged cerebral tissue. PMID:23488559

  20. Critical Limb Ischemia: Reporting Outcomes and Quality

    PubMed Central

    2012-01-01

    The impetus to pursue quality in limb salvage is high in the current economic environment. This has been spurred on by the diffusion of multiple technologies, the lack of well-defined cost-effectiveness benchmarks, and the paucity of process and structure benchmarks. Furthermore, no national database exists to capture current activity and trends, and lead structure and process changes that could analyze outcomes and improve standards in peripheral interventions for limb salvage. This manuscript examines the challenges in measuring outcomes and quality in limb salvage and explores the components necessary for ensuring quality in limb salvage interventions. PMID:23342183

  1. The evolving concept of physiological ischemia training vs. ischemia preconditioning.

    PubMed

    Ni, Jun; Lu, Hongjian; Lu, Xiao; Jiang, Minghui; Peng, Qingyun; Ren, Caili; Xiang, Jie; Mei, Chengyao; Li, Jianan

    2015-11-01

    Ischemic heart diseases are the leading cause of death with increasing numbers of patients worldwide. Despite advances in revascularization techniques, angiogenic therapies remain highly attractive. Physiological ischemia training, which is first proposed in our laboratory, refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for about 4 weeks for the sake of triggering molecular and cellular mechanisms to promote angiogenesis and formation of collateral vessels and protect remote ischemia areas. Physiological ischemia training therapy augments angiogenesis in the ischemic myocardium by inducing differential expression of proteins involved in energy metabolism, cell migration, protein folding, and generation. It upregulates the expressions of vascular endothelial growth factor, and induces angiogenesis, protects the myocardium when infarction occurs by increasing circulating endothelial progenitor cells and enhancing their migration, which is in accordance with physical training in heart disease rehabilitation. These findings may lead to a new approach of therapeutic angiogenesis for patients with ischemic heart diseases. On the basis of the promising results in animal studies, studies were also conducted in patients with coronary artery disease without any adverse effect in vivo, indicating that physiological ischemia training therapy is a safe, effective and non-invasive angiogenic approach for cardiovascular rehabilitation. Preconditioning is considered to be the most protective intervention against myocardial ischemia-reperfusion injury to date. Physiological ischemia training is different from preconditioning. This review summarizes the preclinical and clinical data of physiological ischemia training and its difference from preconditioning. PMID:26664354

  2. The Dichotomy of Endoplasmic Reticulum Stress Response in Liver Ischemia-Reperfusion Injury.

    PubMed

    Zhou, Haomming; Zhu, Jianjun; Yue, Shi; Lu, Ling; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Wang, Xuehao; Zhai, Yuan

    2016-02-01

    Endoplasmic reticulum (ER) stress plays critical roles in the pathogenesis of liver ischemia-reperfusion injury (IRI). As ER stress triggers an adaptive cellular response, the question of what determines its functional outcome in liver IRI remains to be defined. In a murine liver partial warm ischemia model, we studied how transient (30 minutes) or prolonged (90 minutes) liver ischemia regulated local ER stress response and autophagy activities and their relationship with liver IRI. Effects of chemical chaperon 4-phenylbutyrate (4-PBA) or autophagy inhibitor 3-methyladenine (3-MA) were evaluated. Our results showed that although the activating transcription factor 6 branch of ER stress response was induced in livers by both types of ischemia, liver autophagy was activated by transient, but inhibited by prolonged, ischemia. Although 3-MA had no effects on liver IRI after prolonged ischemia, it significantly increased liver IRI after transient ischemia. The 4-PBA treatment protected livers from IRI after prolonged ischemia by restoring autophagy flux, and the adjunctive 3-MA treatment abrogated its liver protective effect. The same 4-PBA treatment, however, increased liver IRI and disrupted autophagy flux after transient ischemia. Although both types of ischemia activated 5' adenosine monophosphate-activated protein kinase and inactivated protein kinase B (Akt), prolonged ischemia also resulted in downregulations of autophagy-related gene 3 and autophagy-related gene 5 in ischemic livers. These results indicate a functional dichotomy of ER stress response in liver IRI via its regulation of autophagy. Transient ischemia activates autophagy to protect livers from IRI, whereas prolonged ischemia inhibits autophagy to promote the development of liver IRI. PMID:26683513

  3. Radiological Evaluation of Bowel Ischemia.

    PubMed

    Dhatt, Harpreet S; Behr, Spencer C; Miracle, Aaron; Wang, Zhen Jane; Yeh, Benjamin M

    2015-11-01

    Intestinal ischemia, which refers to insufficient blood flow to the bowel, is a potentially catastrophic entity that may require emergent intervention or surgery in the acute setting. Although the clinical signs and symptoms of intestinal ischemia are nonspecific, computed tomography (CT) findings can be highly suggestive in the correct clinical setting. In our article, we review the CT diagnosis of arterial, venous, and nonocclusive intestinal ischemia. We discuss the vascular anatomy, pathophysiology of intestinal ischemia, CT techniques for optimal imaging, key and ancillary radiological findings, and differential diagnosis. PMID:26526436

  4. Murine Model of Intestinal Ischemia-reperfusion Injury.

    PubMed

    Gubernatorova, Ekaterina O; Perez-Chanona, Ernesto; Koroleva, Ekaterina P; Jobin, Christian; Tumanov, Alexei V

    2016-01-01

    Intestinal ischemia is a life-threatening condition associated with a broad range of clinical conditions including atherosclerosis, thrombosis, hypotension, necrotizing enterocolitis, bowel transplantation, trauma and chronic inflammation. Intestinal ischemia-reperfusion (IR) injury is a consequence of acute mesenteric ischemia, caused by inadequate blood flow through the mesenteric vessels, resulting in intestinal damage. Reperfusion following ischemia can further exacerbate damage of the intestine. The mechanisms of IR injury are complex and poorly understood. Therefore, experimental small animal models are critical for understanding the pathophysiology of IR injury and the development of novel therapies. Here we describe a mouse model of acute intestinal IR injury that provides reproducible injury of the small intestine without mortality. This is achieved by inducing ischemia in the region of the distal ileum by temporally occluding the peripheral and terminal collateral branches of the superior mesenteric artery for 60 min using microvascular clips. Reperfusion for 1 hr, or 2 hr after injury results in reproducible injury of the intestine examined by histological analysis. Proper position of the microvascular clips is critical for the procedure. Therefore the video clip provides a detailed visual step-by-step description of this technique. This model of intestinal IR injury can be utilized to study the cellular and molecular mechanisms of injury and regeneration. PMID:27213580

  5. Ischemia causes muscle fatigue.

    PubMed

    Murthy, G; Hargens, A R; Lehman, S; Rempel, D M

    2001-05-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue. PMID:11398857

  6. Ischemia causes muscle fatigue

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  7. Oligodendrogenesis after cerebral ischemia

    PubMed Central

    Zhang, Ruilan; Chopp, Michael; Zhang, Zheng Gang

    2013-01-01

    Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle of adult rodent brain generate oligodendrocyte progenitor cells (OPCs) that disperse throughout the corpus callosum and striatum where some of OPCs differentiate into mature oligodendrocytes. Studies in animal models of stroke demonstrate that cerebral ischemia induces oligodendrogenesis during brain repair processes. This article will review evidence of stroke-induced proliferation and differentiation of OPCs that are either resident in white matter or are derived from SVZ neural progenitor cells and of therapies that amplify endogenous oligodendrogenesis in ischemic brain. PMID:24194700

  8. [Myocardial responses to ischemia].

    PubMed

    Borisenko, V G; Gubareva, E A; Kade, A Kh

    2010-01-01

    The paper details the types of a myocardial response to impaired blood flow, such as myocardial stunning, hibernation, ischemic preconditioning, warm-up phenomenon, ischemic postconditioning, remodeling, and infarction. According to the pathogenesis, the authors identify several types of myocardial dysfunction in transient ischemic attack--uptake, delivery; and a mixed one. It is concluded the myocardial response to damage depends on a combination of influencing factors, a number of pathophysiological processes starting in the acute phase of ischemia achieve its peak in the late period. PMID:20564927

  9. Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps

    PubMed Central

    Nguyen, Gerard K.; Monahan, John F. W.; Davis, Gabrielle B.; Lee, Yong Suk; Ragina, Neli P.; Wang, Charles; Zhou, Zhao Y.; Hong, Young Kwon; Spivak, Ryan M.; Wong, Alex K.

    2013-01-01

    The field of reconstructive microsurgery is experiencing tremendous growth, as evidenced by recent advances in face and hand transplantation, lower limb salvage after trauma, and breast reconstruction. Common to all of these procedures is the creation of a nutrient vascular supply by microsurgical anastomosis between a single artery and vein. Complications related to occluded arterial inflow and obstructed venous outflow are not uncommon, and can result in irreversible tissue injury, necrosis, and flap loss. At times, these complications are challenging to clinically determine. Since early intervention with return to the operating room to re-establish arterial inflow or venous outflow is key to flap salvage, the accurate diagnosis of early stage complications is essential. To date, there are no biochemical markers or serum assays that can predict these complications. In this study, we utilized a rat model of flap ischemia in order to identify the transcriptional signatures of venous congestion and arterial ischemia. We found that the critical ischemia time for the superficial inferior epigastric fasciocutaneus flap was four hours and therefore performed detailed analyses at this time point. Histolgical analysis confirmed significant differences between arterial and venous ischemia. The transcriptome of ischemic, congested, and control flap tissues was deciphered by performing Affymetrix microarray analysis and verified by qRT-PCR. Principal component analysis revealed that arterial ischemia and venous congestion were characterized by distinct transcriptomes. Arterial ischemia and venous congestion was characterized by 408 and 1536>2-fold differentially expressed genes, respectively. qRT-PCR was used to identify five candidate genes Prol1, Muc1, Fcnb, Il1b, and Vcsa1 to serve as biomarkers for flap failure in both arterial ischemia and venous congestion. Our data suggests that Prol1 and Vcsa1 may be specific indicators of venous congestion and allow clinicians to

  10. Neutrophils--a key component of ischemia-reperfusion injury.

    PubMed

    Schofield, Zoe Victoria; Woodruff, Trent Martin; Halai, Reena; Wu, Mike Chia-Lun; Cooper, Matthew Allister

    2013-12-01

    Ischemia-reperfusion injury (IRI) is a common occurrence following myocardial infarction, transplantation, stroke, and trauma that can lead to multiple organ failure, which remains the foremost cause of death in critically ill patients. Current therapeutic strategies for IRI are mainly palliative, and there is an urgent requirement for a therapeutic that could prevent or reverse tissue damage caused by IRI. Neutrophils are the primary responders following ischemia and reperfusion and represent important components in the protracted inflammatory response and severity associated with IRI. Experimental studies demonstrate neutrophil infiltration at the site of ischemia and show that inducing neutropenia can protect organs from IRI. In this review, we highlight the mechanisms involved in neutrophil recruitment, activation, and adherence and how this contributes to disease severity in IRI. Inhibiting neutrophil mobilization, tissue recruitment, and ultimately neutrophil-associated activation of local and systemic inflammatory responses may have therapeutic potential in the amelioration of local and remote tissue damage following IRI. PMID:24088997

  11. Sphingolipid Therapy in Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Gundewar, Susheel; Lefer, David J.

    2009-01-01

    Sphingolipids are known to play a significant physiological role in cell growth, cell differentiation, and critical signal transduction pathways. Recent studies have demonstrated a significant role of sphingolipids and their metabolites in the pathogenesis of myocardial ischemia-reperfusion injury. Our laboratory has investigated the cytoprotective effects of N,N,N-Trimethylsphingosine chloride (TMS), a stable N-methylated synthetic sphingolipid analogue on myocardial and hepatic ischemia reperfusion injury in clinically relevant in vivo murine models of ischemia-reperfusion injury. TMS administered intravenously at the onset of ischemia reduced myocardial infarct size in the wild-type and obese (ob/ob) mice. Following myocardial I/R, there was an improvement in cardiac function in the wild-type mice. Additionally, TMS also decreased serum liver enzymes following hepatic I/R in wild-type mice. The cytoprotective effects did not extend to the ob/ob mice following hepatic I/R or to the db/db mice following both myocardial and hepatic I/R. Our data suggests that although TMS is cytoprotective following I/R in normal animals, the cytoprotective actions of TMS are largely attenuated in obese and diabetic animals which may be due to altered signaling mechanisms in these animal models. Here we review the therapeutic role of TMS and other sphingolipids in the pathogenesis of myocardial ischemia reperfusion injury and their possible mechanisms of cardioprotection. PMID:17928150

  12. Purinergic signalling in brain ischemia.

    PubMed

    Pedata, Felicita; Dettori, Ilaria; Coppi, Elisabetta; Melani, Alessia; Fusco, Irene; Corradetti, Renato; Pugliese, Anna Maria

    2016-05-01

    Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia a primary damage due to the early massive increase of extracellular glutamate is followed by activation of resident immune cells, i.e microglia, and production or activation of inflammation mediators. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. Extracellular concentrations of ATP and adenosine in the brain increase dramatically during ischemia in concentrations able to stimulate their respective specific P2 and P1 receptors. Both ATP P2 and adenosine P1 receptor subtypes exert important roles in ischemia. Although adenosine exerts a clear neuroprotective effect through A1 receptors during ischemia, the use of selective A1 agonists is hampered by undesirable peripheral effects. Evidence up to now in literature indicate that A2A receptor antagonists provide protection centrally by reducing excitotoxicity, while agonists at A2A (and possibly also A2B) and A3 receptors provide protection by controlling massive infiltration and neuroinflammation in the hours and days after brain ischemia. Among P2X receptors most evidence indicate that P2X7 receptor contribute to the damage induced by the ischemic insult due to intracellular Ca(2+) loading in central cells and facilitation of glutamate release. Antagonism of P2X7 receptors might represent a new treatment to attenuate brain damage and to promote proliferation and maturation of brain immature resident cells that can promote tissue repair following cerebral ischemia. Among P2Y receptors, antagonists of P2Y12 receptors are of value because of their antiplatelet activity and possibly because of additional anti-inflammatory effects. Moreover strategies that modify adenosine or ATP concentrations at injury sites might be of value to limit damage after ischemia. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and

  13. [Cerebral ischemia in young adults].

    PubMed

    Berlit, P; Endemann, B; Vetter, P

    1991-08-01

    An overview is given over etiology and prognosis of cerebral ischemias until the age of 40. In a time period of 19 years, 168 patients were diagnosed with cerebral ischemia until the age of 40 (91 females, 77 males). The most frequent etiology is premature atherosclerosis in patients with vascular risk factors (up to 50%). Cardiogenic embolism is responsible for 1 to 34% of the cases: cardiac valve diseases and endocarditis being the most frequent sources. In 2 to 19% a vasculitis is diagnosed. While infectious arteritis is especially frequent in countries of the third world, immunovasculitides are common in Europe and the USA. Noninflammatory vasculopathies include spontaneous or traumatic dissection, fibromuscular dysplasia and vascular malformations. A migrainous stroke is especially frequent in female smokers with intake of oral contraceptives. During pregnancy both sinus thrombosis and arterial ischemia occur. Hematologic causes for ischemia are polycythemia, thrombocytosis and genetic diseases (sickle cell anemia, AT3-deficiency). Cerebral ischemia may occur in connection with the ingestion of ergot-derivates. The prognosis of cerebral ischemia in young adults is better than in older stroke-patients. PMID:1937340

  14. Local and Remote Postconditioning Decrease Intestinal Injury in a Rabbit Ischemia/Reperfusion Model

    PubMed Central

    Yang, Mu; Dong, Jian-Xin; Li, Lu-Bin; Che, Hai-Jie; Yong, Jun; Song, Fu-Bo; Wang, Tao; Zhang, Jv-Wen

    2016-01-01

    Intestinal ischemia/reperfusion (I/R) injury is a significant problem that is associated with high morbidity and mortality in critical settings. This injury may be ameliorated using postconditioning protocol. In our study, we created a rabbit intestinal I/R injury model to analyze the effects of local ischemia postconditioning (LIPo) and remote ischemia postconditioning (RIPo) on intestinal I/R injury. We concluded that LIPo affords protection in intestinal I/R injury in a comparable fashion with RIPo by decreasing oxidative stress, neutrophil activation, and apoptosis. PMID:26819600

  15. Solid organ abdominal ischemia, part I: clinical features, etiology, imaging findings, and management.

    PubMed

    Ricci, Zina J; Oh, Sarah K; Stein, Marjorie W; Kaul, Bindu; Flusberg, Milana; Chernyak, Victoria; Rozenblit, Alla M; Mazzariol, Fernanda A

    2016-01-01

    Solid organ abdominal ischemia commonly presents with acute pain prompting radiologic evaluation and often requires urgent treatment. Despite different risk factors and anatomic differences, most solid organ ischemia is due to arterial or venous occlusion and, less frequently, a low-flow state. Radiologic diagnosis is critical, as clinical presentations are often nonspecific. Contrast-enhanced computed tomography (CT) is the modality of choice (except in adnexal torsion) with magnetic resonance imaging (MRI) useful in equivocal cases or follow-up of ischemic disease. This article will provide a pictorial review of the CT and MRI features of solid abdominal organ ischemia while highlighting key clinical features, etiology, and management. PMID:27317217

  16. Hollow organ abdominal ischemia, part II: clinical features, etiology, imaging findings and management.

    PubMed

    Ricci, Zina J; Mazzariol, Fernanda S; Kaul, Bindu; Oh, Sarah K; Chernyak, Victoria; Flusberg, Milana; Stein, Marjorie W; Rozenblit, Alla M

    2016-01-01

    Acute hollow organ ischemia commonly presents with acute pain prompting radiologic evaluation and almost always requires urgent treatment. Despite different risk factors and anatomic differences, ischemia is commonly due to low flow states but can also be due to arterial and venous occlusion. Radiologic diagnosis is critical as many present with nonspecific symptoms. Contrast-enhanced computed tomography (CT) is the modality of choice. Magnetic resonance imaging (MRI) is preferred in suspected appendicitis in pregnant patients and is superior in biliary necrosis. This article provides a pictorial review of the CT/MRI features of hollow abdominal organ ischemia while highlighting key clinical features, pathogenesis, and management. PMID:27317221

  17. Protective effects of sevoflurane in hepatic ischemia-reperfusion injury.

    PubMed

    Li, Ji; Yuan, Tong; Zhao, Xin; Lv, Guo-Yue; Liu, Huan-Qiu

    2016-06-01

    The endothelial glycocalyx plays a critical role in the regulation of vascular structure and functions. Previous studies have demonstrated that sevoflurane, a volatile anesthetic, can preserve the endothelial glycocalyx in heart tissues against ischemia-reperfusion injury. However, little is known about the effects of sevoflurane pretreatment on the vascular structure and functions of liver tissues following ischemia-reperfusion injury. To this end, female Sprague-Dawley rats (n = 28) were anesthetized either with ketamine (80-120 mg/kg, i.p.) or with one minimum alveolar concentration (MAC) sevoflurane (2% v/v). Following in vivo hepatic ischemia procedure, the liver was isolated and reperfusion was produced. During the period of reperfusion, liver reperfusion samples were collected, and the concentrations of heparan sulfate and syndecan-1 (Syn-1), and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes, were measured. The morphology of hepatocytes and endothelial glycocalyx were then assessed by using the light and electron microscopies, respectively. Ischemia-reperfusion increased the release of HS and Syn-1, and elevated the levels of ALT and AST in a time-dependent manner. However, sevoflurane pretreatment reduced the release of HS and Syn-1and attenuated the levels of ALT and AST, in a time-dependent manner, as compared with ketamine pretreatment. Furthermore, sevoflurane pretreatment decreased the shedding of endothelial glycocalyx and hepatocytes necrosis. Sevoflurane pretreatment preserved the endothelial glycocalyx in the liver tissue against ischemia-reperfusion injury. The effect appears to help protect hepatocytes against ischemia-reperfusion-induced necrosis. PMID:26966142

  18. Long-term follow-up of patients with silent ischemia during exercise radionuclide angiography

    SciTech Connect

    Breitenbuecher, A.P.; Pfisterer, M.; Hoffmann, A.; Burckhardt, D. )

    1990-04-01

    A retrospective 5 year follow-up study was performed in 140 patients with unequivocal ischemia during exercise radionuclide angiography (greater than or equal to 10% decrease in left ventricular ejection fraction or greater than or equal to 5% decrease in ejection fraction together with a distinct regional wall motion abnormality). In 84 patients (60%), ischemia during radionuclide angiography was silent (silent ischemia group), whereas 56 patients experienced angina during the test (symptomatic group). Work load and antianginal medication were similar in both groups. Critical cardiac events (unstable angina, myocardial infarction, cardiac death) occurred in 27% of patients in the silent ischemia group and 16% of those in the symptomatic group (p = NS); however, myocardial infarction or death was more frequent in patients with silent ischemia (22% versus 9%; p less than 0.05). If there was additional exercise-induced ST segment depression, the rate of critical events was further increased (p less than 0.05). The difference in critical cardiac events seemed to be influenced by the higher incidence of revascularization procedures in symptomatic patients, whereas medical therapy had no similar effect. Thus, these findings suggest that patients with documented severe ischemia should undergo left heart catheterization and revascularization irrespective of symptoms to improve their prognosis.

  19. Animal models of cerebral ischemia

    NASA Astrophysics Data System (ADS)

    Khodanovich, M. Yu.; Kisel, A. A.

    2015-11-01

    Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

  20. Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy

    NASA Astrophysics Data System (ADS)

    Goel, Utsav O.; Maddox, Michael M.; Elfer, Katherine N.; Dorsey, Philip J.; Wang, Mei; McCaslin, Ian Ross; Brown, J. Quincy; Lee, Benjamin R.

    2014-10-01

    Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

  1. Controversies in cardiovascular care: silent myocardial ischemia

    NASA Technical Reports Server (NTRS)

    Hollenberg, N. K.

    1987-01-01

    The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.

  2. Noninvasive Multimodal Imaging to Predict Recovery of Locomotion after Extended Limb Ischemia

    PubMed Central

    Radowsky, Jason S.; Caruso, Joseph D.; Luthra, Rajiv; Bradley, Matthew J.; Elster, Eric A.; Forsberg, Jonathan A.; Crane, Nicole J.

    2015-01-01

    Acute limb ischemia is a common cause of morbidity and mortality following trauma both in civilian centers and in combat related injuries. Rapid determination of tissue viability and surgical restoration of blood flow are desirable, but not always possible. We sought to characterize the response to increasing periods of hind limb ischemia in a porcine model such that we could define a period of critical ischemia (the point after which irreversible neuromuscular injury occurs), evaluate non-invasive methods for characterizing that ischemia, and establish a model by which we could predict whether or not the animal’s locomotion would return to baselines levels post-operatively. Ischemia was induced by either application of a pneumatic tourniquet or vessel occlusion (performed by clamping the proximal iliac artery and vein at the level of the inguinal ligament). The limb was monitored for the duration of the procedure with both 3-charge coupled device (3CCD) and infrared (IR) imaging for tissue oxygenation and perfusion, respectively. The experimental arms of this model are effective at inducing histologically evident muscle injury with some evidence of expected secondary organ damage, particularly in animals with longer ischemia times. Noninvasive imaging data shows excellent correlation with post-operative functional outcomes, validating its use as a non-invasive means of viability assessment, and directly monitors post-occlusive reactive hyperemia. A classification model, based on partial-least squares discriminant analysis (PLSDA) of imaging variables only, successfully classified animals as “returned to normal locomotion” or “did not return to normal locomotion” with 87.5% sensitivity and 66.7% specificity after cross-validation. PLSDA models generated from non-imaging data were not as accurate (AUC of 0.53) compared the PLSDA model generated from only imaging data (AUC of 0.76). With some modification, this limb ischemia model could also serve as a

  3. Oxidative Stress and Lung Ischemia-Reperfusion Injury

    PubMed Central

    Ferrari, Renata Salatti; Andrade, Cristiano Feijó

    2015-01-01

    Ischemia-reperfusion (IR) injury is directly related to the formation of reactive oxygen species (ROS), endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients. PMID:26161240

  4. Intestinal ischemia in neonates and children.

    PubMed

    Jeican, Ionuţ Isaia; Ichim, Gabriela; Gheban, Dan

    2016-01-01

    The article reviews the intestinal ischemia theme on newborn and children. The intestinal ischemia may be either acute - intestinal infarction (by vascular obstruction or by reduced mesenteric blood flow besides the occlusive mechanism), either chronic. In neonates, acute intestinal ischemia may be caused by aortic thrombosis, volvulus or hypoplastic left heart syndrome. In children, acute intestinal ischemia may be caused by fibromuscular dysplasia, volvulus, abdominal compartment syndrome, Burkitt lymphoma, dermatomyositis (by vascular obstruction) or familial dysautonomia, Addison's disease, situs inversus abdominus (intraoperative), burns, chemotherapy administration (by nonocclusive mesenteric ischemia). Chronic intestinal ischemia is a rare condition in pediatrics and can be seen in abdominal aortic coarctation or hypoplasia, idiopathic infantile arterial calcinosis. PMID:27547054

  5. Intestinal ischemia in neonates and children

    PubMed Central

    JEICAN, IONUŢ ISAIA; ICHIM, GABRIELA; GHEBAN, DAN

    2016-01-01

    The article reviews the intestinal ischemia theme on newborn and children. The intestinal ischemia may be either acute - intestinal infarction (by vascular obstruction or by reduced mesenteric blood flow besides the occlusive mechanism), either chronic. In neonates, acute intestinal ischemia may be caused by aortic thrombosis, volvulus or hypoplastic left heart syndrome. In children, acute intestinal ischemia may be caused by fibromuscular dysplasia, volvulus, abdominal compartment syndrome, Burkitt lymphoma, dermatomyositis (by vascular obstruction) or familial dysautonomia, Addison’s disease, situs inversus abdominus (intraoperative), burns, chemotherapy administration (by nonocclusive mesenteric ischemia). Chronic intestinal ischemia is a rare condition in pediatrics and can be seen in abdominal aortic coarctation or hypoplasia, idiopathic infantile arterial calcinosis. PMID:27547054

  6. Leg ischemia post-varicocelectomy

    PubMed Central

    Al-Wahbi, Abdullah M; Elmoukaied, Shaza

    2016-01-01

    Varicocelectomy is the most commonly performed operation for the treatment of male infertility. Many surgical approaches are used as each of them has advantages over the other and is preferred by surgeons. Vascular injury has never been reported as a complication of varicocelectomy apart from testicular artery injury. We present a 36-year-old male who developed leg ischemia post-varicocelectomy due to common femoral artery injury. He was successfully treated by using a vein graft. PMID:27022305

  7. Predictive Modeling of Cardiac Ischemia

    NASA Technical Reports Server (NTRS)

    Anderson, Gary T.

    1996-01-01

    The goal of the Contextual Alarms Management System (CALMS) project is to develop sophisticated models to predict the onset of clinical cardiac ischemia before it occurs. The system will continuously monitor cardiac patients and set off an alarm when they appear about to suffer an ischemic episode. The models take as inputs information from patient history and combine it with continuously updated information extracted from blood pressure, oxygen saturation and ECG lines. Expert system, statistical, neural network and rough set methodologies are then used to forecast the onset of clinical ischemia before it transpires, thus allowing early intervention aimed at preventing morbid complications from occurring. The models will differ from previous attempts by including combinations of continuous and discrete inputs. A commercial medical instrumentation and software company has invested funds in the project with a goal of commercialization of the technology. The end product will be a system that analyzes physiologic parameters and produces an alarm when myocardial ischemia is present. If proven feasible, a CALMS-based system will be added to existing heart monitoring hardware.

  8. Neuroglobin Protection in Retinal Ischemia

    PubMed Central

    Chan, Anita S.Y.; Saraswathy, Sindhu; Rehak, Matus; Ueki, Mari

    2012-01-01

    Purpose. Neuroglobin (Ngb) is a vertebrate globin that is predominantly expressed in the retina and brain. To explore the role of Ngb in retinal neuroprotection during ischemia reperfusion (IR), the authors examined the effect of Ngb overexpression in the retina in vivo by using Ngb-transgenic (Ngb-Tg) mice. Methods. Retinal IR was induced in Ngb overexpressing Ngb-Tg mice and wild type (WT) mice by cannulating the anterior chamber and transiently elevating the IOP for 60 minutes. After Day 7 of reperfusion, the authors evaluated Ngb mRNA and protein expression in nonischemic control as well as ischemic mice and its effect on retinal histology, mitochondrial oxidative stress, and apoptosis, using morphometry and immunohistochemistry, quantitative PCR analysis and Western blot techniques. Results. Ngb-Tg mice without ischemia overexpress Ngb mRNA 11.3-fold (SE ± 0.457, P < 0.05) higher than WT control mice, and this overexpression of Ngb protein was localized to the mitochondria of the ganglion cells, outer and inner plexiform layers, and photoreceptor inner segments. This overexpression of Ngb is associated with decreased mitochondrial DNA damage in Ngb-Tg mice with IR in comparison with WT. Ngb-Tg mice with IR also revealed significant preservation of retinal thickness, significantly less activated caspase 3 protein expression, and apoptosis in comparison with WT mice. Conclusions. Neuroglobin overexpression plays a neuroprotective role against retinal ischemia reperfusion injury due to decreasing of mitochondrial oxidative stress-mediated apoptosis. PMID:22167093

  9. Gastric Tissue Damage Analysis Generated by Ischemia: Bioimpedance, Confocal Endomicroscopy, and Light Microscopy

    PubMed Central

    Beltran, Nohra E.; Garcia, Laura E.; Garcia-Lorenzana, Mario

    2013-01-01

    The gastric mucosa ischemic tissular damage plays an important role in critical care patients' outcome, because it is the first damaged tissue by compensatory mechanism during shock. The aim of the study is to relate bioimpedance changes with tissular damage level generated by ischemia by means of confocal endomicroscopy and light microscopy. Bioimpedance of the gastric mucosa and confocal images were obtained from Wistar male rats during basal and ischemia conditions. They were anesthetized, and stain was applied (fluorescein and/or acriflavine). The impedance spectroscopy catheter was inserted and then confocal endomicroscopy probe. After basal measurements and biopsy, hepatic and gastric arteries clamping induced ischemia. Finally, pyloric antrum tissue was preserved in buffered formaldehyde (10%) for histology processing using light microscopy. Confocal images were equalized, binarized, and boundary defined, and infiltrations were quantified. Impedance and infiltrations increased with ischemia showing significant changes between basal and ischemia conditions (P < 0.01). Light microscopy analysis allows detection of general alterations in cellular and tissular integrity, confirming gastric reactance and confocal images quantification increments obtained during ischemia. PMID:23841094

  10. MLC901, a traditional Chinese medicine protects the brain against global ischemia.

    PubMed

    Quintard, H; Borsotto, M; Veyssiere, J; Gandin, C; Labbal, F; Widmann, C; Lazdunski, M; Heurteaux, C

    2011-09-01

    Global ischemia leads to damage in the hippocampal CA1 region and is associated with behavioral deficits. NeuroAid (MLC601 and MLC901), a Traditional Chinese Medicine is used in China for patients after stroke. We have investigated here the effects of MLC901 on brain injury and deficits after global ischemia in the rat. Global ischemia induced by four-vessel occlusion resulted in degeneration of CA1 neurons. MLC901 (0.074 mg/ml) prevented both necrosis and apoptosis of neurons up to 3 h after ischemia. These positive MLC901 effects were associated with a decrease in Bax expression and in levels of the lipid peroxidation product malondialdehyde. Using the PI3-kinase inhibitor LY294002 we also demonstrated the critical role of the Akt pathway in MLC901-mediated neuroprotection. MLC901 enhanced neurogenesis. Furthermore, MLC901 improved functional recovery of rats after global ischemia as assessed by the Morris water maze. In this test MLC901 reduced the increase in escape latency and in swim distance induced by ischemia. MLC901 also improved post-ischemic grip strength. If observations made with rats can be extended to humans, then MLC901 will represent a novel therapeutic strategy after cardiac arrest with a clinically interesting time window of protection. PMID:21605573

  11. Life- and limb-threatening infections following the use of an external fixator.

    PubMed

    Jauregui, J J; Bor, N; Thakral, R; Standard, S C; Paley, D; Herzenberg, J E

    2015-09-01

    External fixation is widely used in orthopaedic and trauma surgery. Infections around pin or wire sites, which are usually localised, non-invasive, and are easily managed, are common. Occasionally, more serious invasive complications such as necrotising fasciitis (NF) and toxic shock syndrome (TSS) may occur. We retrospectively reviewed all patients who underwent external fixation between 1997 and 2012 in our limb lengthening and reconstruction programme. A total of eight patients (seven female and one male) with a mean age of 20 years (5 to 45) in which pin/wire track infections became limb- or life-threatening were identified. Of these, four were due to TSS and four to NF. Their management is described. A satisfactory outcome was obtained with early diagnosis and aggressive medical and surgical treatment. Clinicians caring for patients who have external fixation and in whom infection has developed should be aware of the possibility of these more serious complications. Early diagnosis and aggressive treatment are required in order to obtain a satisfactory outcome. PMID:26330600

  12. Limb-threatening and life-threatening diabetic extremities: clinical patterns and outcomes in 56 patients.

    PubMed

    Bahebeck, Jean; Sobgui, Eugene; Loic, Fonkoue; Fonfoe, Loic; Nonga, Bernadette Ngo; Mbanya, Jean Claude; Sosso, Maurice

    2010-01-01

    Limb- and life-threatening hand and foot infections in diabetic patients account for a large proportion of amputations and a substantial number of deaths. Between August 2006 and the end of July 2008, we conducted a prospective cohort study of consecutive diabetic patients with serious hand or foot infections, in an effort to identify clinical patterns and outcomes related to the treatment of these infections. Infections were categorized as dry, gas, and wet gangrene; necrotizing fasciitis or cellulitis; acute extensive osteomyelitis; and any of these infections involving the hand. All of the patients underwent a standard examination and treatment protocol, although none of the patients received vascular surgical care. End points included healing following debridement or minor amputation, major (transtibial or more proximal) amputation, or death. A total of 56 patients were included in the final analyses, and their mean age was 70 (range 51 to 86) years. Of the patients, 17 (30.36%) had necrotizing cellulitis, 12 (21.43%) had wet gangrene, 9 (16.07%) had acute extensive osteomyelitis, 5 (8.93%) had dry gangrene, 5 (8.93%) had gas gangrene, 4 (7.14%) had necrotizing fasciitis, and 4 (7.14) had diffuse hand infections. Five (8.93%) patients died (2 after prior amputation), 26 (46.43%) underwent debridement and/or minor amputation, and 27 (48.21%) required major amputations. Based on our findings, we concluded that 7 patterns of serious limb- or life-threatening infection were identified and, in the absence of vascular surgical intervention, mortality can be reduced at the expense of more amputations. PMID:20123286

  13. Animal models of cerebral ischemia for evaluation of drugs.

    PubMed

    Gupta, Y K; Briyal, Seema

    2004-10-01

    Stroke is a major cause of death and disability worldwide. The resulting burden on the society continues to grow, with increase in the incidence of stroke. Brain attack is a term introduced to describe the acute presentation of stroke, which emphasizes the need for urgent action to remedy the situation. Though a large number of therapeutic agents like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or being evaluated, there remains a large gap between the benefits by these agents and properties an ideal drug for stroke should offer. In recent years much attention is being paid towards the exploration of herbal preparation, antioxidant agents and combination therapies including COX-2 inhibitors in experimental model of stroke. For better evaluation of the drugs and enhancement of their predictability from animal experimentation to clinical settings, it has been realized that the selection of animal models, the parameters to be evaluated should be critically assessed. Focal and global cerebral ischemia represents diseases that are common in the human population. Understanding the mechanisms of injury and neuroprotection in these diseases is important to learn new target sites to treat ischemia. There are many animal models available to investigate injury mechanisms and neuroprotective strategies. In this article we attempted to summarize commonly explored animal models of focal and global cerebral ischemia and evaluate their advantages and limitations. PMID:15907047

  14. [Ischemia-reperfusion injury after lung transplantation].

    PubMed

    Gennai, Stéphane; Pison, Christophe; Briot, Raphaël

    2014-09-01

    Lung ischemia-reperfusion is characterized by diffuse alveolar damage arising from the first hours after transplantation. The first etiology of the primary graft dysfunction in lung is ischemia-reperfusion. It is burdened by an important morbi-mortality. Lung ischemia-reperfusion increases the oxidative stress, inactivates the sodium pump, increases the intracellular calcium, leads to cellular death and the liberation of pro-inflammatory mediators. Researches relative to the reduction of the lung ischemia-reperfusion injuries are numerous but few of them found a place in common clinical practice, because of an insufficient level of proofs. Ex vivolung evaluation is a suitable technique in order to evaluate therapeutics supposed to limit lung ischemia-reperfusion injuries. PMID:24935680

  15. Metabolic Adaptation to Muscle Ischemia

    NASA Technical Reports Server (NTRS)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  16. Thrombolysis and neuroprotection in cerebral ischemia.

    PubMed

    Gutiérrez, M; Díez Tejedor, E; Alonso de Leciñana, M; Fuentes, B; Carceller, F; Roda, J M

    2006-01-01

    Stroke is a major cause of death and disability worldwide. The resulting burden on society grows with the increase in the incidence of stroke. The term brain attack was introduced to describe the acute presentation of stroke and emphasize the need for urgent action to remedy the situation. Though a large number of therapeutic agents, like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or are being evaluated, there is still a large gap between the benefits of these agents and the properties of an ideal drug for stroke. So far, only thrombolysis with rtPA within a 3-hour time window has been shown to improve the outcome of patients with ischemic stroke. Understanding the mechanisms of injury and neuroprotection in these diseases is important to target news sites for treating ischemia. Better evaluation of the drugs and increased similarity between the results of animal experimentation and in the clinical setting requires critical assessment of the selection of animal models and the parameters to be evaluated. Our laboratory has employed a rat embolic stroke model to investigate the combination of rtPA with citicoline as compared to monotherapy alone and investigated whether neuroprotection should be provided before or after thrombolysis in order to achieve a greater reduction of ischemic brain damage. PMID:16651822

  17. CERAMIDE AND MITOCHONDRIA IN ISCHEMIA/REPERFUSION

    PubMed Central

    Novgorodov, Sergei A.; Gudz, Tatyana I.

    2009-01-01

    A hallmark of tissue injury in various models of ischemia/reperfusion (IR) is mitochondrial dysfunction and the release of mitochondrial pro-apoptotic proteins leading to cell death. Although IR-induced mitochondrial injury has been extensively studied and key mitochondrial functions affected by IR are chiefly characterized, the nature of the molecule that causes loss of mitochondrial integrity and function remains obscure. It has become increasingly clear that ceramide, a membrane sphingolipid and a key mediator of cell-stress responses could play a critical role in IR-induced mitochondrial damage. Emerging data point to excessive ceramide accumulation in tissue and, specifically, in mitochondria after IR. Exogenously added to isolated mitochondria, ceramide could mimic some of the mitochondrial dysfunctions occurring in IR. The recent identification and characterization of major enzymes in ceramide synthesis is expected to contribute to the understanding of molecular mechanisms of ceramide involvement in mitochondrial damage in IR. This review will examine the experimental evidence supporting the important role of ceramide in mitochondrial dysfunction in IR in order to highlight potential targets for pharmacological manipulation of ceramide levels. PMID:19247196

  18. Cerebral ischemia during surgery: an overview

    PubMed Central

    Zhou, Zhi-Bin; Meng, Lingzhong; Gelb, Adrian W; Lee, Roger; Huang, Wen-Qi

    2016-01-01

    Abstract Cerebral ischemia is the pathophysiological condition in which the oxygenated cerebral blood flow is less than what is needed to meet cerebral metabolic demand. It is one of the most debilitating complications in the perioperative period and has serious clinical sequelae. The monitoring and prevention of intraoperative cerebral ischemia are crucial because an anesthetized patient in the operating room cannot be neurologically assessed. In this paper, we provide an overview of the definition, etiology, risk factors, and prevention of cerebral ischemia during surgery.

  19. Kupffer cell activation after no-flow ischemia versus hemorrhagic shock.

    PubMed

    Jaeschke, Hartmut; Farhood, Anwar

    2002-07-15

    Kupffer cell-derived oxidant stress is critical for reperfusion injury after no-flow ischemia. However, the importance of Kupffer cells as source of reactive oxygen formation is unclear in a hemorrhagic shock model. Therefore, we evaluated Kupffer cell activation after 60 or 120 min of hemorrhage and 90 min of resuscitation (HS/RS) in pentobarbital-anesthetized male Fischer rats. Plasma glutathione disulfide (GSSG) as indicator for a vascular oxidant stress showed no significant changes after HS/RS. Plasma ALT activities were only moderately increased (100-200 U/L). Kupffer cells isolated from postischemic livers did not generate more superoxide than cells from sham controls. In contrast, the 10-fold increase of plasma GSSG and the 9-fold higher spontaneous superoxide formation of Kupffer cells after 60 min of hepatic no-flow ischemia followed by 90 min of reperfusion demonstrated the activation of Kupffer cells in this experimental model. Plasma ALT activities (1930 +/- 240 U/L) indicated severe liver injury. These results demonstrate a fundamental difference in the degree of Kupffer cell activation between the two models of warm hepatic ischemia. Our findings suggest that different therapeutic strategies are necessary to ameliorate the initial injury after low flow ischemia (hemorrhage) compared to cold (transplantation) or warm (Pringle maneuver) no-flow ischemia. PMID:12106817

  20. Analysis of temporal dynamics in imagery during acute limb ischemia and reperfusion

    NASA Astrophysics Data System (ADS)

    Irvine, John M.; Regan, John; Spain, Tammy A.; Caruso, Joseph D.; Rodriquez, Maricela; Luthra, Rajiv; Forsberg, Jonathon; Crane, Nicole J.; Elster, Eric

    2014-03-01

    Ischemia and reperfusion injuries present major challenges for both military and civilian medicine. Improved methods for assessing the effects and predicting outcome could guide treatment decisions. Specific issues related to ischemia and reperfusion injury can include complications arising from tourniquet use, such as microvascular leakage in the limb, loss of muscle strength and systemic failures leading to hypotension and cardiac failure. Better methods for assessing the viability of limbs/tissues during ischemia and reducing complications arising from reperfusion are critical to improving clinical outcomes for at-risk patients. The purpose of this research is to develop and assess possible prediction models of outcome for acute limb ischemia using a pre-clinical model. Our model relies only on non-invasive imaging data acquired from an animal study. Outcome is measured by pathology and functional scores. We explore color, texture, and temporal features derived from both color and thermal motion imagery acquired during ischemia and reperfusion. The imagery features form the explanatory variables in a model for predicting outcome. Comparing model performance to outcome prediction based on direct observation of blood chemistry, blood gas, urinalysis, and physiological measurements provides a reference standard. Initial results show excellent performance for the imagery-base model, compared to predictions based direct measurements. This paper will present the models and supporting analysis, followed by recommendations for future investigations.

  1. Modulation of NADPH oxidase activation in cerebral ischemia/reperfusion injury in rats.

    PubMed

    Genovese, Tiziana; Mazzon, Emanuela; Paterniti, Irene; Esposito, Emanuela; Bramanti, Placido; Cuzzocrea, Salvatore

    2011-02-01

    NADPH oxidase is a major complex that produces reactive oxygen species (ROSs) during the ischemic period and aggravates brain damage and cell death after ischemic injury. Although many approaches have been tested for preventing production of ROSs by NADPH oxidase in ischemic brain injury, the regulatory mechanisms of NADPH oxidase activity after cerebral ischemia are still unclear. The aim of this study is identifying apocynin as a critical modulator of NADPH oxidase and elucidating its role as a neuroprotectant in an experimental model of brain ischemia in rat. Treatment of apocynin 5min before of reperfusion attenuated cerebral ischemia in rats. Administration of apocynin showed marked reduction in infarct size compared with that of control rats. Medial carotid artery occlusion (MCAo)-induced cerebral ischemia was also associated with an increase in, nitrotyrosine formation, as well as IL-1β expression, IκB degradation and ICAM expression in ischemic regions. These expressions were markedly inhibited by the treatment of apocynin. We also demonstrated that apocynin reduces levels of apoptosis (TUNEL, Bax and Bcl-2 expression) resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. This new understanding of apocynin induced adaptation to ischemic stress and inflammation could suggest novel avenues for clinical intervention during ischemic and inflammatory diseases. PMID:21138737

  2. Perioperative myocardial ischemia reperfusion injury.

    PubMed

    Shernan, Stanton K

    2003-09-01

    Myocardial I-R injury contributes to adverse cardiovascular outcomes after cardiac surgery. The pathogenesis of I-R injury is complex and involves the activation, coordination, and amplification of several systemic and local proinflammatory pathways (Fig. 4). Treatment and prevention of perioperative morbidity associated with myocardial I-R will ultimately require a multifocal approach. Combining preoperative risk stratification (co-morbidity and surgical complexity), minimizing initiating factors predisposing to SIRS, limiting ischemia duration, and administering appropriate immunotherapy directed toward systemic and local proinflammatory mediators of I-R injury, should all be considered. In addition, the role of the genetic-environmental interactions in the pathogenesis of cardiovascular disease is also being examined. Thus, in the near future, preoperative screening for polymorphisms of certain inflammatory and coagulation genes should inevitably help reduce morbidity by permitting the identification of high-risk cardiac surgical patients and introducing the opportunity for gene therapy or pharmacogenetic intervention [42,64]. PMID:14562561

  3. The surgical treatment of chronic intestinal ischemia.

    PubMed Central

    Eklof, B; Hoevels, J; Ihse, I

    1978-01-01

    The mortality in acute intestinal ischemia is high, and 50% of such patients have previous attacks of abdominal angina due to chronic intestinal ischemia. Vascular reconstruction is remarkably successful in relieving the symptoms of chronic intesintal ischemia and for this reason angiographic examination is recommended in all patients in whom chronic intestinal ischemia is suspected. If the diagnosis is established by arteriography with appropriate supporting evidence, vascular reconstruction should be performed. Images Fig. 1a and b. Fig. 2a and b. Fig. 3b and c. Fig. 4a. Fig. 4b. Fig. 5b. Fig. 6. Fig. 7a. Fig. 7b and c. Fig. 8a and b. Fig. 9a. Fig. 9b. Fig. 9c. PMID:637591

  4. Diagnosis of acute cardiac ischemia.

    PubMed

    Pope, J Hector; Selker, Harry P

    2003-02-01

    A better understanding of coronary syndromes allow physicians to appreciate UAP and AMI as part of a continuum of ACI. ACI is a life-threatening condition whose identification can have major economic and therapeutic importance as far as threatening dysrhythmias and preventing or limiting myocardial infarction size. The identification of ACI continues to challenge the skill of even experienced clinicians, yet physicians continue (appropriately) to admit the overwhelming majority of patients with ACI; in the process, they admit many patients without acute ischemia [2], overestimating the likelihood of ischemia in low-risk patients because of magnified concern for this diagnosis for prognostic and therapeutic reasons. Studies of admitting practices from a decade ago have yielded useful clinical information but have shown that neither clinical symptoms nor the ECG could reliably distinguish most patients with ACI from those with other conditions. Most studies have evaluated the accuracy of various technologies for diagnosing ACI, yet only a few have evaluated the clinical impact of routine use. The prehospital 12-lead ECG has moderate sensitivity and specificity for the diagnosis of ACI. It has demonstrated a reduction of the mean time to thrombolysis by 33 minutes and short-term overall mortality in randomized trials. In the general ED setting, only the ACI-TIPI has demonstrated, in a large-scale multicenter clinical trial, a reduction in unnecessary hospitalizations without decreasing the rate of appropriate admission for patients with ACI. The Goldman chest pain protocol has good sensitivity for AMI but was not shown to result in any differences in hospitalization rate, length of stay, or estimated costs in the single clinical impact study performed. The protocol's applicability to patients with UAP has not been evaluated. Single measurement of biomarkers at presentation to the ED has poor sensitivity for AMI, although most biomarkers have high specificity. Serial

  5. The transcriptome of cerebral ischemia

    PubMed Central

    VanGilder, Reyna L.; Huber, Jason D.; Rosen, Charles L.; Barr, Taura L.

    2015-01-01

    The molecular causality and response to stroke is complex. Yet, much of the literature examining the molecular response to stroke has focused on targeted pathways that have been well-characterized. Consequently, our understanding of stroke pathophysiology has made little progress by way of clinical therapeutics since tissue plasminogen activator was approved for treatment nearly a decade ago. The lack of clinical translation is in part due to neuron-focused studies, preclinical models of cerebral ischemia and the paradoxical nature of neuro-inflammation. With the evolution of the Stroke Therapy Academic Industry Roundtable criteria streamlining research efforts and broad availability of genomic technologies, the ability to decipher the molecular fingerprint of ischemic stroke is on the horizon. This review highlights preclinical microarray findings of the ischemic brain, discusses the transcriptome of cerebral preconditioning and emphasizes the importance of further characterizing the role of the neurovascular unit and peripheral white blood cells in mediating stroke damage and repair within the penumbra. PMID:22381515

  6. Echocardiographic assessment of myocardial ischemia

    PubMed Central

    Dworrak, Birgit; Sanchis-Gomar, Fabian; Lucia, Alejandro; Buck, Thomas; Erbel, Raimund

    2016-01-01

    Over the last 60 years, echocardiography has emerged as a dominant and indispensable technique for the detection and assessment of coronary heart disease (CHD). In this review, we will describe and discuss this powerful tool of cardiology, especially in the hands of an experienced user, with a focus on myocardial ischemia. Technical development is still on-going, and various new ultrasound techniques have been established in the field of echocardiography in the last several years, including tissue Doppler imaging (TDI), contrast echocardiography, three-dimensional echocardiography (3DE), and speckle tracking echocardiography (i.e., strain/strain rate-echocardiography). High-end equipment with harmonic imaging, high frame rates and the opportunity to adjust mechanical indices has improved imaging quality. Like all new techniques, these techniques must first be subjected to comprehensive scientific assessment, and appropriate training that accounts for physical and physiological limits should be provided. These limits will constantly be redefined as echocardiographic techniques continue to change, which will present new challenges for the further development of ultrasound technology. PMID:27500160

  7. Non-occlusive mesenteric ischemia.

    PubMed

    Lock, G; Schölmerich, J

    1995-07-01

    Non-occlusive disease of the mesentery is still a rather underdiagnosed and underestimated condition. It is associated with circumstances that may compromise circulation or the intake of drugs that may lower mesenteric blood flow. Pathophysiologically, a "low flow syndrome" of mesenteric circulation is followed by vasoconstriction; a reperfusion injury may contribute to the ischemic injury. Histopathological changes vary between superficial localized lesions and transmural gangrene. Diagnosis within the initial 24 hours of the development of symptoms is crucial for prognosis but remains a difficult task. Clinical presentation, laboratory tests and ultrasound lack specificity; the role of duplex ultrasound, tonometry and reflectance spectophotometry is still under evaluation. Mesenteric angiography remains the only reliable diagnostic tool and should be applied early in all patients in whom acute mesenteric ischemia is a real possibility. Therapy is aimed at the rapid correction of predisposing and precipitating factors and an effective treatment of mesenteric vasoconstriction. Treatment of choice is a papaverine infusion into the superior mesenteric artery via an angiography catheter. Patients with peritoneal signs have to be treated surgically. PMID:7590571

  8. Echocardiographic assessment of myocardial ischemia.

    PubMed

    Leischik, Roman; Dworrak, Birgit; Sanchis-Gomar, Fabian; Lucia, Alejandro; Buck, Thomas; Erbel, Raimund

    2016-07-01

    Over the last 60 years, echocardiography has emerged as a dominant and indispensable technique for the detection and assessment of coronary heart disease (CHD). In this review, we will describe and discuss this powerful tool of cardiology, especially in the hands of an experienced user, with a focus on myocardial ischemia. Technical development is still on-going, and various new ultrasound techniques have been established in the field of echocardiography in the last several years, including tissue Doppler imaging (TDI), contrast echocardiography, three-dimensional echocardiography (3DE), and speckle tracking echocardiography (i.e., strain/strain rate-echocardiography). High-end equipment with harmonic imaging, high frame rates and the opportunity to adjust mechanical indices has improved imaging quality. Like all new techniques, these techniques must first be subjected to comprehensive scientific assessment, and appropriate training that accounts for physical and physiological limits should be provided. These limits will constantly be redefined as echocardiographic techniques continue to change, which will present new challenges for the further development of ultrasound technology. PMID:27500160

  9. Tolerance of the Human Kidney to Isolated Controlled Ischemia

    PubMed Central

    Weinberg, Joel M.; Ercole, Barbara; Torkko, Kathleen C.; Hilton, William; Bennett, Michael; Devarajan, Prasad; Venkatachalam, Manjeri A.

    2013-01-01

    Tolerance of the human kidney to ischemia is controversial. Here, we prospectively studied the renal response to clamp ischemia and reperfusion in humans, including changes in putative biomarkers of AKI. We performed renal biopsies before, during, and after surgically induced renal clamp ischemia in 40 patients undergoing partial nephrectomy. Ischemia duration was >30 minutes in 82.5% of patients. There was a mild, transient increase in serum creatinine, but serum cystatin C remained stable. Renal functional changes did not correlate with ischemia duration. Renal structural changes were much less severe than observed in animal models that used similar durations of ischemia. Other biomarkers were only mildly elevated and did not correlate with renal function or ischemia duration. In summary, these data suggest that human kidneys can safely tolerate 30–60 minutes of controlled clamp ischemia with only mild structural changes and no acute functional loss. PMID:23411786

  10. Can superoxide dismutase prevent postburn dermal ischemia?

    PubMed

    Tan, Q; Ma, W X; Wang, L; Chen, H R

    1997-05-01

    Decreasing progressive dermal ischemia after burning could theoretically limit the amount of skin necrosis. It is controversial whether the use of free radical scavengers could prevent the progressive dermal ischemia of the postburn stasis zone. We evaluated the effect of superoxide dismutase (SOD) on preventing postburn dermal ischemia in animal models by the India ink perfusion and skin transparent preparation techniques. The closely clipped backs of guinea-pigs were bathed in 75 degrees C water for 10 s. Within 5 min postburn, SOD-treated groups were administered SOD (10,000 u/kg) intra-peritoneally every 6 h. All animals were perfused with 70 per cent India ink via cervical artery cannula by 16 kPa constant pressure at 0, 8, 16, 24 h postburn, and the skin transparent preparations were made, while the level of malonyl dialdehyde (MDA) in skin tissue was assessed. The results showed that with prolongation of postburn time, the rate of filling of India ink in skin capillary plexuses decreased gradually (p < 0.01). MDA increased continuously, which was related to postburn dermal ischemia (r = 0.689, p < 0.01). Though the level of MDA decreased in SOD-treated groups, the India ink filling rates showed no significant difference between controls and experimental groups (p > 0.05). The results were also confirmed by observation of skin transparent preparations and TEM. This study suggests that superoxide dismutase fails to prevent progressive dermal ischemia after burning. PMID:9232283

  11. Assessment of Renal Ischemia By Optical Spectroscopy

    SciTech Connect

    Fitzgerald, J T; Demos, S; Michalopoulou, A; Pierce, J L; Troppmann, C

    2004-01-07

    Introduction: No reliable method currently exists for quantifying the degree of warm ischemia in kidney grafts prior to transplantation. We describe a method for evaluating pretransplant warm ischemia time using optical spectroscopic methods. Methods: Lewis rat kidney vascular pedicles were clamped unilaterally in vivo for 0, 5, 10, 20, 30, 60, 90 or 120 minutes; 8 animals were studied at each time point. Injured and contra-lateral control kidneys were then flushed with Euro-Collins solution, resected and placed on ice. 335 nm excitation autofluorescence as well as cross polarized light scattering images were taken of each injured and control kidney using filters of various wavelengths. The intensity ratio of the injured to normal kidneys was compared to ischemia time. Results: Autofluorescence intensity ratios through a 450 nm filter and light scattering intensity ratios through an 800 nm filter both decreased significantly with increasing ischemia time (p < 0.0001 for each method, one-way ANOVA). All adjacent and non-adjacent time points between 0 and 90 minutes were distinguishable using one of these two modalities by Fisher's PLSD. Conclusions: Optical spectroscopic methods can accurately quantify warm ischemia time in kidneys that have been subsequently hypothermically preserved. Further studies are needed to correlate results with physiological damage and posttransplant performance.

  12. Infrared laser hemotherapy in cerebral ischemia modeling

    NASA Astrophysics Data System (ADS)

    Musienko, Julia I.; Nechipurenko, Natalia I.

    2003-10-01

    Use of intravenous laser irradiation of blood (ILIB) is considered to be the most effective method of laser therapy and its application is expedient pathogenetically in the ischemic disturbances. The aim of this study is to investigate ILIB influence with infrared laser (IL) with 860 nm wavelength on hemostasis, acid-base status (ABS) of blood in normal rabbits and after modeling of local ischemia of brain (LIB). Experimental cerebral ischemia is characterized by development of hypercoagulation syndrom and metabolic acidosis. ILIB with infrared radiation of 2.0 mW power provokes hypocoagulation in intact animals. Application of ILIB in rabbits after LIB contributes for hemostasis and acid-base status normalizing compared to operated animals. IL radiation with 8,5 mW power results in marked hemostatic activation in all animals. Therefore, beneficial effect of low power laser radiation (LPLR) manifests in narrow power diapason in experimental brain ischemia.

  13. Pulsed electromagnetic field improves postnatal neovascularization in response to hindlimb ischemia.

    PubMed

    Li, Rui-Lin; Huang, Jing-Juan; Shi, Yi-Qin; Hu, An; Lu, Zhao-Yang; Weng, Liang; Wang, Shen-Qi; Han, Yi-Peng; Zhang, Lan; Hao, Chang-Ning; Duan, Jun-Li

    2015-01-01

    Pulsed electromagnetic fields (PEMF) have been shown to promote proliferation and regeneration in the damaged tissue. Here, we examined whether PEMF therapy improved postnatal neovascularization using murine model of hindlimb ischemia, and the underlying cellular/molecular mechanisms were further investigated. Hindlimb ischemia was induced by unilateral femoral artery resection using 6-8 week-old male C57BL6 mice. Then, mice were exposed to extracorporeal PEMF therapy (4 cycles, 8min/cycle, 30 ± 3 Hz, 5 mT) every day until day 14. Our data demonstrated that PEMF therapy significantly accelerated wound healing, decreased prevalence of gangrene and increased postnatal neovascularization. Moreover, the levels of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) and Akt phosphorylation in ischemic muscles were markedly enhanced following PEMF therapy. In vitro, PEMF inhibited the process of hypoxia-induced apoptosis and augmented tube formation, migration and proliferative capacities of human umbilical vein endothelial cells (HUVECs). Additionally, PEMF exposure increased VEGF secretion, as well as the eNOS and Akt phosphorylation, and these benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. In conclusion, our data indicated that PEMF therapy enhanced ischemia-mediated angiogenesis, through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway. Therefore, PEMF should be a valuable treatment for the patients with critical limb ischemia. PMID:26045885

  14. Pulsed electromagnetic field improves postnatal neovascularization in response to hindlimb ischemia

    PubMed Central

    Li, Rui-Lin; Huang, Jing-Juan; Shi, Yi-Qin; Hu, An; Lu, Zhao-Yang; Weng, Liang; Wang, Shen-Qi; Han, Yi-Peng; Zhang, Lan; Hao, Chang-Ning; Duan, Jun-Li

    2015-01-01

    Pulsed electromagnetic fields (PEMF) have been shown to promote proliferation and regeneration in the damaged tissue. Here, we examined whether PEMF therapy improved postnatal neovascularization using murine model of hindlimb ischemia, and the underlying cellular/molecular mechanisms were further investigated. Hindlimb ischemia was induced by unilateral femoral artery resection using 6-8 week-old male C57BL6 mice. Then, mice were exposed to extracorporeal PEMF therapy (4 cycles, 8min/cycle, 30 ± 3 Hz, 5 mT) every day until day 14. Our data demonstrated that PEMF therapy significantly accelerated wound healing, decreased prevalence of gangrene and increased postnatal neovascularization. Moreover, the levels of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) and Akt phosphorylation in ischemic muscles were markedly enhanced following PEMF therapy. In vitro, PEMF inhibited the process of hypoxia-induced apoptosis and augmented tube formation, migration and proliferative capacities of human umbilical vein endothelial cells (HUVECs). Additionally, PEMF exposure increased VEGF secretion, as well as the eNOS and Akt phosphorylation, and these benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. In conclusion, our data indicated that PEMF therapy enhanced ischemia-mediated angiogenesis, through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway. Therefore, PEMF should be a valuable treatment for the patients with critical limb ischemia. PMID:26045885

  15. The Effects of Antecedent Exercise on Motor Function Recovery and Brain-derived Neurotrophic Factor Expression after Focal Cerebral Ischemia in Rats

    PubMed Central

    Kim, Gyeyeop; Kim, Eunjung

    2013-01-01

    [Purpose] In the present study, we investigated the effect of antecedent exercise on functional recovery and brain-derived neurotrophic factor (BDNF) expression following focal cerebral ischemia injury. [Subjects] The rat middle cerebral artery occlusion (MCAO) model was employed. Adult male Sprague-Dawley rats were randomly divided into 4 groups. Group I included untreated normal rats (n=10); Group II included untreated rats with focal cerebral ischemia (n=10); Group III included rats that performed treadmill exercise (20 m/min) training after focal cerebral ischemia (n=10); and Group IV included rats that performed antecedent treadmill exercise (20 m/min) training before focal cerebral ischemia (n=10) as well as treadmill exercise after ischemia. At different time points (1, 7, 14, and 21 days) Garcia’s score, and the hippocampal expressions level of BDNF were examined. [Results] In the antecedent exercise group, improvements in the motor behavior index (Garcia’s score) were observed and hippocampal BDNF protein expression levels increased. [Conclusion] These results indicate that antecedent treadmill exercise, before permanent brain ischemia exerts a neuroprotective effect against ischemia brain injury by improving motor performance and increasing the level of BDNF expression. Furthermore, the antecedent treadmill exercise of appropriate intensity is critical for post-stroke rehabilitation. PMID:24259800

  16. Update and validation of the Society for Vascular Surgery wound, ischemia, and foot infection threatened limb classification system.

    PubMed

    Mills, Joseph L

    2014-03-01

    The diagnosis of critical limb ischemia, first defined in 1982, was intended to delineate a patient cohort with a threatened limb and at risk for amputation due to severe peripheral arterial disease. The influence of diabetes and its associated neuropathy on the pathogenesis-threatened limb was an excluded comorbidity, despite its known contribution to amputation risk. The Fontaine and Rutherford classifications of limb ischemia severity have also been used to predict amputation risk and the likelihood of tissue healing. The dramatic increase in the prevalence of diabetes mellitus and the expanding techniques of arterial revascularization has prompted modification of peripheral arterial disease classification schemes to improve outcomes analysis for patients with threatened limbs. The diabetic patient with foot ulceration and infection is at risk for limb loss, with abnormal arterial perfusion as only one determinant of outcome. The wound extent and severity of infection also impact the likelihood of limb loss. To better predict amputation risk, the Society for Vascular Surgery Lower Extremity Guidelines Committee developed a classification of the threatened lower extremity that reflects these important clinical considerations. Risk stratification is based on three major factors that impact amputation risk and clinical management: wound, ischemia, and foot infection. This classification scheme is relevant to the patient with critical limb ischemia because many are also diabetic. Implementation of the wound, ischemia, and foot infection classification system in critical limb ischemia patients is recommended and should assist the clinician in more meaningful analysis of outcomes for various forms of wound and arterial revascularizations procedures required in this challenging, patient population. PMID:25812755

  17. Polyamine metabolism in rat myocardial ischemia-reperfusion injury.

    PubMed

    Han, Liping; Xu, Changqing; Guo, Yimin; Li, Hongzhu; Jiang, Chunming; Zhao, Yajun

    2009-02-01

    This study was focused on investigating the involvement of polyamine metabolism in the myocardial ischemia-reperfusion injury (MIRI) in an in vivo rat model. A branch of the descending left coronary artery was occluded for 30 min followed by 2 h, 6 h, 12 h, and 24 h reperfusion. Then the expression of spermidine/spermine N1-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) and the concentrations of polyamines were assessed. It was found that the expression of SSAT and ODC were upregulated after reperfusion and the concentrations of spermidine and spermine were significantly decreased, while putrescine concentration was significantly increased. The results suggest that MIRI may cause disturbance of polyamine metabolism, and it may play a critical role in MIRI. PMID:18077014

  18. The role of neutrophils in myocardial ischemia-reperfusion injury.

    PubMed

    Jordan, J E; Zhao, Z Q; Vinten-Johansen, J

    1999-09-01

    Reperfusion of ischemic myocardium is necessary to salvage tissue from eventual death. However, reperfusion after even brief periods of ischemia is associated with pathologic changes that represent either an acceleration of processes initiated during ischemia per se, or new pathophysiological changes that were initiated after reperfusion. This 'reperfusion injury' shares many characteristics with inflammatory responses in the myocardium. Neutrophils feature prominently in this inflammatory component of postischemic injury. Ischemia-reperfusion prompts a release of oxygen free radicals, cytokines and other proinflammatory mediators that activate both the neutrophils and the coronary vascular endothelium. Activation of these cell types promotes the expression of adhesion molecules on both the neutrophils and endothelium, which recruits neutrophils to the surface of the endothelium and initiate a specific cascade of cell-cell interactions, leading first to adherence of neutrophils to the vascular endothelium, followed later by transendothelial migration and direct interaction with myocytes. This specific series of events is a prerequisite to the phenotypic expression of reperfusion injury, including endothelial dysfunction, microvascular collapse and blood flow defects, myocardial infarction and apoptosis. Pharmacologic therapy can target the various components in this critical series of events. Effective targets for these pharmacologic agents include: (a) inhibiting the release or accumulation of proinflammatory mediators, (b) altering neutrophil or endothelial cell activation and (c) attenuating adhesion molecule expression on endothelium, neutrophils and myocytes. Monoclonal antibodies to adhesion molecules (P-selectin, L-selectin, CD11, CD18), complement fragments and receptors attenuate neutrophil-mediated injury (vascular injury, infarction), but clinical application may encounter limitations due to antigen-antibody reactions with the peptides. Humanized

  19. Pre- and Perinatal Ischemia-Hypoxia, the Ischemia-Hypoxia Response Pathway, and ADHD Risk.

    PubMed

    Smith, Taylor F; Schmidt-Kastner, Rainald; McGeary, John E; Kaczorowski, Jessica A; Knopik, Valerie S

    2016-05-01

    This review focuses on how measured pre- and perinatal environmental and (epi)genetic risk factors are interrelated and potentially influence one, of many, common developmental pathway towards ADHD. Consistent with the Developmental Origins of Health and Disease hypothesis, lower birth weight is associated with increased ADHD risk. Prenatal ischemia-hypoxia (insufficient blood and oxygen supply in utero) is a primary pathway to lower birth weight and produces neurodevelopmental risk for ADHD. To promote tissue survival in the context of ischemia-hypoxia, ischemia-hypoxia response (IHR) pathway gene expression is altered in the developing brain and peripheral tissues. Although altered IHR gene expression is adaptive in the context of ischemia-hypoxia, lasting IHR epigenetic modifications may lead to increased ADHD risk. Taken together, IHR genetic vulnerability to ischemia-hypoxia and IHR epigenetic alterations following prenatal ischemia-hypoxia may result in neurodevelopmental vulnerability for ADHD. Limitations of the extant literature and future directions for genetically-informed research are discussed. PMID:26920003

  20. [SURGICAL TREATMENT OF AN ACUTE MESENTERIAL ISCHEMIA].

    PubMed

    Shepehtko, E N; Garmash, D A; Kurbanov, A K; Marchenko, V O; Kozak, Yu S

    2016-04-01

    Experience of surgical treatment of 143 patients, suffering an acute mesenterial ischemia, was summarized. Isolated intestinal resection was performed in 41 patients (lethality 65.9%), intestinal resection with the mesenterial vessels thrombembolectomy--in 9 (lethality 33.3%). After performance of the combined intervention postoperative lethality was in two times lower, than after isolated intestinal resection. PMID:27434952

  1. [Platelets, atherothrombosis, antiplatelet drugs and cerebral ischemia].

    PubMed

    Bousser, Marie-Germaine

    2013-02-01

    Platelets play a much more important role in myocardial ischemia than in cerebral ischemia, because atherothrombosis - the underlying cause of the vast majority of myocardial infarcts - is responsible for only 25-30% of cerebral infarcts. Aspirin is the only effective antiplatelet drug for primary prevention of ischemic events, especially those affecting the heart. For secondary prevention of cerebral infarction, clopidogrel and the combination of aspirin with extended-release dipyridamole are both marginally better than aspirin alone, but aspirin remains the gold standard worldwide because of its remarkable cost/benefit/tolerability ratio. The clopidogrel-aspirin combination is to be avoided because of the risk of hemorrhage, particularly in the brain and gastrointestinal tract. Revascularization strategies and the choice of antiplatelet drugs for the acute phase of myocardial and cerebral ischemia are very different, consisting of endovascular treatment and aggressive platelet inhibition for coronary infarcts, versus intravenous thrombolysis and / or aspirin for cerebral infarcts. None of the new antiplatelet drugs used in acute coronary syndromes has so far been studied in acute cerebral ischemia. PMID:24919368

  2. [Myocardial ischemia-reperfusion injury and melatonin].

    PubMed

    Sahna, Engin; Deniz, Esra; Aksulu, Hakki Engin

    2006-06-01

    It is believed that myocardial ischemia-reperfusion injury is related to increased free radical generated and intracellular calcium overload especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger, antioxidant and can inhibit the intracellular calcium overload. In this review, we have summarized the fundamental of cardiac ischemia-reperfusion injury and the effects of melatonin on myocardial damage that related to cardiac ischemia-reperfusion injury. The total antioxidant capacity of human serum is related to melatonin levels. Incidence of sudden cardiac death is high in the morning hours. It has been shown that melatonin levels are significantly low at these times and patients with coronary heart disease have lower than normal individuals. These findings thought that melatonin would be valuable to test in clinical trials for prevention of possible ischemia-reperfusion-induced injury, especially life threatening arrhythmias and infarct size, effecting life quality, associated with thrombolysis, angioplasty, coronary artery spasm or coronary bypass surgery. PMID:16766282

  3. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice

    PubMed Central

    Le Clef, Nathalie; Verhulst, Anja; D’Haese, Patrick C.; Vervaet, Benjamin A.

    2016-01-01

    Acute kidney injury (AKI) is an underestimated, yet important risk factor for development of chronic kidney disease (CKD). Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD). Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis) is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care) with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data. PMID:27007127

  4. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

    PubMed

    Le Clef, Nathalie; Verhulst, Anja; D'Haese, Patrick C; Vervaet, Benjamin A

    2016-01-01

    Acute kidney injury (AKI) is an underestimated, yet important risk factor for development of chronic kidney disease (CKD). Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD). Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis) is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care) with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data. PMID:27007127

  5. Effects of pulmonary ischemia on lung morphology.

    PubMed

    Fields, Michael J; Bishai, John M; Mitzner, Wayne; Wagner, Elizabeth M

    2007-07-01

    Pulmonary ischemia resulting from chronic pulmonary embolism leads to proliferation of the systemic circulation within and surrounding the lung. However, it is not clear how well alveolar tissue is sustained during the time of complete pulmonary ischemia. In the present study, we investigated how pulmonary ischemia after left pulmonary artery ligation (LPAL) would alter lung mechanical properties and morphology. In this established mouse model of lung angiogenesis after chronic LPAL (10), we evaluated lung function and structure before (3 days) and after (14 days) a functional systemic circulation to the left lung is established. Age-matched naïve and sham-operated C57Bl/6 mice and mice undergoing chronic LPAL were studied. Left and right lung pressure-volume relationships were determined. Next, lungs were inflated in situ with warmed agarose (25-30 cmH(2)O) and fixed, and mean chord lengths (MCL) of histological sections were quantified. MCL of naïve mice averaged 43.9 +/- 1.8 mum. No significant changes in MCL were observed at either time point after LPAL. Left lung volumes and specific compliances were significantly reduced 3 days after LPAL. However, by 14 days after LPAL, lung pressure-volume relationships were not different from controls. These results suggest that severe pulmonary ischemia causes changes in lung mechanics early after LPAL that are reversed by the time a new systemic vasculature is known to perfuse pulmonary capillaries. The LPAL model thus affords a unique opportunity to study lung functional responses to tissue ischemia and subsequent recovery. PMID:17449796

  6. Wnt Agonist Attenuates Liver Injury and Improves Survival after Hepatic Ischemia/Reperfusion

    PubMed Central

    Kuncewitch, Michael; Yang, Weng-Lang; Molmenti, Ernesto; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

    2012-01-01

    The Wnt/β-catenin signaling pathway is well characterized in stem cell biology and plays a critical role in liver development, regeneration, and homeostasis. We hypothesized that pharmacological activation of Wnt signaling protects against hepatic ischemia/reperfusion (I/R) injury through its known proliferative and anti-apoptotic properties. Sprague-Dawley rats underwent 70% hepatic ischemia by microvascular clamping of the hilum of the left and median lobes of the liver for 90 min, followed by reperfusion. Wnt agonist (2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine, 5 mg/kg BW) or vehicle (20% DMSO in saline) in 0.5 ml was injected intraperitoneally (i.p.) 1 h prior to ischemia or infused intravenously over 30 min right after ischemia. Blood and tissue samples from the pre-treated groups were collected 24 h after reperfusion, and a survival study was performed. Hepatic expression of β-catenin and its downstream target gene Axin2 were decreased after I/R while Wnt agonist restored their expression to sham levels. Wnt agonist blunted I/R-induced elevations of AST, ALT, and LDH and significantly improved the microarchitecture of the liver. The cell proliferation determined by Ki67 immunostaining significantly increased with Wnt agonist treatment and inflammatory cascades were dampened in Wnt agonist-treated animals, as demonstrated by attenuations in IL-6, myeloperoxdase, iNOS and nitrotyrosine. Wnt agonist also significantly decreased the amount of apoptosis, as evidenced by decreases in both TUNEL staining as well as caspase-3 activity levels. Finally, the 10-day survival rate was increased from 27% in the vehicle group to 73% in the pre-treated Wnt agonist group and 55% in the Wnt agonist post-ischemia treatment group. Thus, we propose that direct Wnt/β-catenin stimulation may represent a novel therapeutic approach in the treatment of hepatic I/R. PMID:23143067

  7. Neutralization of interleukin-18 ameliorates ischemia/reperfusion-induced myocardial injury.

    PubMed

    Venkatachalam, Kaliyamurthi; Prabhu, Sumanth D; Reddy, Venkatapuram Seenu; Boylston, William H; Valente, Anthony J; Chandrasekar, Bysani

    2009-03-20

    Ischemia/reperfusion (I/R) injury is characterized by the induction of oxidative stress and proinflammatory cytokine expression. Recently demonstrating that oxidative stress and TNF-alpha each stimulate interleukin (IL)-18 expression in cardiomyocytes, we hypothesized that I/R also induces IL-18 expression and thus exacerbates inflammation and tissue damage. Neutralization of IL-18 signaling should therefore diminish tissue injury following I/R. I/R studies were performed using a chronically instrumented closed chest mouse model. Male C57BL/6 mice underwent 30 min of ischemia by LAD coronary artery ligation followed by various periods of reperfusion. Sham-operated or ischemia-only mice served as controls. A subset of animals was treated with IL-18-neutralizing antibodies 1 h prior to LAD ligation. Ischemic LV tissue was used for analysis. Our results demonstrate that, compared with sham operation and ischemia alone, I/R significantly increased (i) oxidative stress (increased MDA/4-HNE levels), (ii) neutrophil infiltration (increased MPO activity), (iii) NF-kappaB DNA binding activity (p50, p65), and (iv) increased expression of IL-18Rbeta, but not IL-18Ralpha or IL-18BP transcripts. Administration of IL-18-neutralizing antibodies significantly reduced I/R injury measured by reduced infarct size (versus control IgG). In isolated adult mouse cardiomyocytes, simulated ischemia/reperfusion enhanced oxidative stress and biologically active IL-18 expression via IKK-dependent NF-kappaB activation. These results indicate that IL-18 plays a critical role in I/R injury and thus represents a promising therapeutic target. PMID:19164288

  8. Neutralization of Interleukin-18 Ameliorates Ischemia/Reperfusion-induced Myocardial Injury*

    PubMed Central

    Venkatachalam, Kaliyamurthi; Prabhu, Sumanth D.; Reddy, Venkatapuram Seenu; Boylston, William H.; Valente, Anthony J.; Chandrasekar, Bysani

    2009-01-01

    Ischemia/reperfusion (I/R) injury is characterized by the induction of oxidative stress and proinflammatory cytokine expression. Recently demonstrating that oxidative stress and TNF-α each stimulate interleukin (IL)-18 expression in cardiomyocytes, we hypothesized that I/R also induces IL-18 expression and thus exacerbates inflammation and tissue damage. Neutralization of IL-18 signaling should therefore diminish tissue injury following I/R. I/R studies were performed using a chronically instrumented closed chest mouse model. Male C57BL/6 mice underwent 30 min of ischemia by LAD coronary artery ligation followed by various periods of reperfusion. Sham-operated or ischemia-only mice served as controls. A subset of animals was treated with IL-18-neutralizing antibodies 1 h prior to LAD ligation. Ischemic LV tissue was used for analysis. Our results demonstrate that, compared with sham operation and ischemia alone, I/R significantly increased (i) oxidative stress (increased MDA/4-HNE levels), (ii) neutrophil infiltration (increased MPO activity), (iii) NF-κB DNA binding activity (p50, p65), and (iv) increased expression of IL-18Rβ, but not IL-18Rα or IL-18BP transcripts. Administration of IL-18-neutralizing antibodies significantly reduced I/R injury measured by reduced infarct size (versus control IgG). In isolated adult mouse cardiomyocytes, simulated ischemia/reperfusion enhanced oxidative stress and biologically active IL-18 expression via IKK-dependent NF-κB activation. These results indicate that IL-18 plays a critical role in I/R injury and thus represents a promising therapeutic target. PMID:19164288

  9. Caveolin-1 protects against hepatic ischemia/reperfusion injury through ameliorating peroxynitrite-mediated cell death.

    PubMed

    Gao, Lei; Chen, Xingmiao; Peng, Tao; Yang, Dan; Wang, Qi; Lv, Zhiping; Shen, Jiangang

    2016-06-01

    Nitrative stress is considered as an important pathological process of hepatic ischemia and reperfusion injury but its regulating mechanisms are largely unknown. In this study, we tested the hypothesis that caveolin-1 (Cav-1), a plasma membrane scaffolding protein, could be an important cellular signaling against hepatic I/R injury through inhibiting peroxynitrite (ONOO(-))-induced cellular damage. Male wild-type mice and Cav-1 knockout (Cav-1(-/-)) were subjected to 1h hepatic ischemia following 1, 6 and 12h of reperfusion by clipping and releasing portal vessels respectively. Immortalized human hepatocyte cell line (L02) was subjected to 1h hypoxia and 6h reoxygenation and treated with Cav-1 scaffolding domain peptide. The major discoveries included: (1) the expression of Cav-1 in serum and liver tissues of wild-type mice was time-dependently elevated during hepatic ischemia-reperfusion injury. (2) Cav-1 scaffolding domain peptide treatment inhibited cleaved caspase-3 expression in the hypoxia-reoxygenated L02 cells; (3) Cav-1 knockout (Cav-1(-/-)) mice had significantly higher levels of serum transaminases (ALT&AST) and TNF-α, and higher rates of apoptotic cell death in liver tissues than wild-type mice after subjected to 1h hepatic ischemia and 6hour reperfusion; (4) Cav-1(-/-) mice revealed higher expression levels of iNOS, ONOO(-) and 3-nitrotyrosine (3-NT) in the liver than wild-type mice, and Fe-TMPyP, a representative peroxynitrite decomposition catalyst (PDC), remarkably reduced level of ONOO(-) and 3-NT and ameliorated the serum ALT, AST and TNF-α levels in both wild-type and Cav-1(-/-) mice. Taken together, we conclude that Cav-1 could play a critical role in preventing nitrative stress-induced liver damage during hepatic ischemia-reperfusion injury. PMID:27021966

  10. ARRB1/β-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia

    PubMed Central

    Wang, Pei; Xu, Tian-Ying; Wei, Kai; Guan, Yun-Feng; Wang, Xia; Xu, Hui; Su, Ding-Feng; Pei, Gang; Miao, Chao-Yu

    2014-01-01

    Autophagy, a highly conserved process conferring cytoprotection against stress, contributes to the progression of cerebral ischemia. β-arrestins are multifunctional proteins that mediate receptor desensitization and serve as important signaling scaffolds involved in numerous physiopathological processes. Here, we show that both ARRB1 (arrestin, β 1) and ARRB2 (arrestin, β 2) were upregulated by cerebral ischemic stress. Knockout of Arrb1, but not Arrb2, aggravated the mortality, brain infarction, and neurological deficit in a mouse model of cerebral ischemia. Accordingly, Arrb1-deficient neurons exhibited enhanced cell injury upon oxygen-glucose deprivation (OGD), an in vitro model of ischemia. Deletion of Arrb1 did not affect the cerebral ischemia-induced inflammation, oxidative stress, and nicotinamide phosphoribosyltransferase upregulation, but markedly suppressed autophagy and induced neuronal apoptosis/necrosis in vivo and in vitro. Additionally, we found that ARRB1 interacted with BECN1/Beclin 1 and PIK3C3/Vps34, 2 major components of the BECN1 autophagic core complex, under the OGD condition but not normal conditions in neurons. Finally, deletion of Arrb1 impaired the interaction between BECN1 and PIK3C3, which is a critical event for autophagosome formation upon ischemic stress, and markedly reduced the kinase activity of PIK3C3. These findings reveal a neuroprotective role for ARRB1, in the context of cerebral ischemia, centered on the regulation of BECN1-dependent autophagosome formation. PMID:24988431

  11. Nampt/PBEF/visfatin exerts neuroprotective effects against ischemia/reperfusion injury via modulation of Bax/Bcl-2 ratio and prevention of caspase-3 activation.

    PubMed

    Erfani, Sohaila; Khaksari, Mehdi; Oryan, Shahrbanoo; Shamsaei, Nabi; Aboutaleb, Nahid; Nikbakht, Farnaz

    2015-05-01

    Nicotinamide phosphoribosyl transferase/pre-B cell colony-enhancing factor/visfatin (Nampt/PBEF/visfatin) is an adipocytokine. By synthesizing nicotinamide adenine dinucleotide (NAD(+)), Nampt/PBEF/visfatin functions to maintain an energy supply that has critical roles in cell survival. Cerebral ischemia leads to energy depletion and eventually neuronal death by apoptosis in specific brain regions specially the hippocampus. However, the role of Nampt/PBEF/visfatin in brain and cerebral ischemia remains to be investigated. This study investigated the role of administration Nampt/PBEF/visfatin in hippocampal CA3 area using a transient global cerebral ischemia model. Both common carotid arteries were occluded for 20 min followed by reperfusion. Saline as a vehicle and Nampt/PBEF/visfatin at a dose of 100 ng were injected intracerebroventricularly (ICV) at the time of cerebral reperfusion. To investigate the underlying mechanisms of Nampt/PBEF/visfatin neuroprotection, levels of expression of apoptosis-related proteins (caspase-3 activation, Bax protein levels, and Bcl-2 protein levels) 96 h after ischemia were determined by immunohistochemical staining. The number of active caspase-3-positive neurons in CA3 was significantly increased in the ischemia group, compared with the sham group (P < 0.001), and treatment with Nampt/PBEF/visfatin significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P < 0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in the ischemia group, compared with the sham group (P < 0.01). However, treatment with Nampt/PBEF/visfatin significantly attenuated the ischemia/reperfusion-induced increase in Bax/Bcl-2 ratio, compared with the ischemia group (P < 0.05). This study has indicated that Nampt/PBEF/visfatin entails neuroprotective effects against ischemia injury when used at the time of cerebral reperfusion. These neuroprotective mechanisms of Nampt

  12. Upper Limb Ischemia: Clinical Experiences of Acute and Chronic Upper Limb Ischemia in a Single Center

    PubMed Central

    Bae, Miju; Chung, Sung Woon; Lee, Chung Won; Choi, Jinseok; Song, Seunghwan; Kim, Sang-pil

    2015-01-01

    Background Upper limb ischemia is less common than lower limb ischemia, and relatively few cases have been reported. This paper reviews the epidemiology, etiology, and clinical characteristics of upper limb ischemia and analyzes the factors affecting functional sequelae after treatment. Methods The records of 35 patients with acute and chronic upper limb ischemia who underwent treatment from January 2007 to December 2012 were retrospectively reviewed. Results The median age was 55.03 years, and the number of male patients was 24 (68.6%). The most common etiology was embolism of cardiac origin, followed by thrombosis with secondary trauma, and the brachial artery was the most common location for a lesion causing obstruction. Computed tomography angiography was the first-line diagnostic tool in our center. Twenty-eight operations were performed, and conservative therapy was implemented in seven cases. Five deaths (14.3%) occurred during follow-up. Twenty patients (57.1%) complained of functional sequelae after treatment. Functional sequelae were found to be more likely in patients with a longer duration of symptoms (odds ratio, 1.251; p=0.046) and higher lactate dehydrogenase (LDH) levels (odds ratio, 1.001; p=0.031). Conclusion An increased duration of symptoms and higher initial serum LDH levels were associated with the more frequent occurrence of functional sequelae. The prognosis of upper limb ischemia is associated with prompt and proper treatment and can also be predicted by initial serum LDH levels. PMID:26290835

  13. Detrimental or beneficial: the role of TRPM2 in ischemia/reperfusion injury

    PubMed Central

    Zhan, Kai-yu; Yu, Pei-lin; Liu, Chun-hui; Luo, Jian-hong; Yang, Wei

    2016-01-01

    Ischemia/reperfusion (I/R) injury is the main cause of tissue damage and dysfunction. I/R injury is characterized by Ca2+ overload and production of reactive oxygen species (ROS), which play critical roles in the process of I/R injury to the brain, heart and kidney, but the underlying mechanisms are largely elusive. Recent evidence demonstrates that TRPM2, a Ca2+-permeable cationic channel and ROS sensor, is involved in I/R injury, but whether TRPM2 plays a protective or detrimental role in this process remains controversial. In this review, we discuss the recent progress in understanding the role of TRPM2 in reperfusion process after brain, heart and kidney ischemia and the potential of targeting TRPM2 for the development of therapeutic drugs to treat I/R injury. PMID:26725732

  14. A Device for Performing Automated Balloon Catheter Inflation Ischemia Studies

    PubMed Central

    Leavesley, Silas J.; Ledkins, Whitley; Rocic, Petra

    2014-01-01

    Coronary collateral growth (arteriogenesis) is a physiological adaptive response to transient and repetitive occlusion of major coronary arteries in which small arterioles (native collaterals) with minimal to no blood flow remodel into larger conduit arteries capable of supplying adequate perfusion to tissue distal to the site of occlusion. The ability to reliably and reproducibly mimic transient, repetitive coronary artery occlusion (ischemia) in animal models is critical to the development of therapies to restore coronary collateral development in type II diabetes and the metabolic syndrome. Current animal models for repetitive coronary artery occlusion implement a pneumatic occluder (balloon) that is secured onto the surface of the heart with the suture, which is inflated manually, via a catheter connected to syringe, to effect occlusion of the left anterior descending coronary artery (LAD). This method, although effective, presents complications in terms of reproducibility and practicality. To address these limitations, we have designed a device for automated, transient inflation of balloon catheters in coronary artery occlusion models. This device allows repeated, consistent inflation (to either specified pressure or volume) and the capability for implementing very complex, month-long protocols. This system has significantly increased the reproducibility of coronary collateral growth studies in our laboratory, resulting in a significant decrease in the numbers of animals needed to complete each study while relieving laboratory personnel from the burden of extra working hours and enabling us to continue studies over periods when we previously could not. In this paper, we present all details necessary for construction and operation of the inflator. In addition, all of the components for this device are commercially available and economical (Table S1). It is our hope that the adoption of automated balloon catheter inflation protocols will improve the experimental

  15. Ischemia detection using Isoelectric Energy Function.

    PubMed

    Kumar, Amit; Singh, Mandeep

    2016-01-01

    A novel method has been proposed for the detection of ischemia using an isoelectric energy function (IEEF) resulting from ST segment deviations in ECG signals. The method consists of five stages: pre-processing, delineation, measurement of isoelectric energy, a beat characterization algorithm and detection of ischemia. The isoelectric energy threshold is used to differentiate ischemic beats from normal beats for ischemic episode detection. Then, ischemic episodes are classified as transmural or subendocardial. The method is validated for recordings of the annotated European ST-T database (EDB). The results show 98.12% average sensitivity (SE) and 98.16% average specificity (SP). These results are significantly better than those of existing methods cited in the literature. The advantage of the proposed method includes simplicity, ruggedness and automatic discarding of noisy beats. PMID:26623944

  16. Endoplasmic reticulum stress in brain ischemia.

    PubMed

    Su, Yingchao; Li, Feng

    2016-08-01

    Endoplasmic reticulum (ER) stress is an intricate mechanism that mediates numerous responses during brain ischemia, thus being essential to determine the fate of neurons. In recent years, studies of the mechanisms of brain ischemic injury have centered on ER stress, glutamate excitotoxicity, dysfunction of mitochondria, inflammatory reactions, calcium overload and death receptor pathways. The role of ER stress is highly important. In addition to resulting in neuronal cell death through calcium toxicity and apoptotic pathways, ER stress also triggers a series of adaptive responses including unfolded protein response (UPR), autophagy, the expression of pro-survival proteins and the enhancement of ER self-repair ability, leading to less ischemic brain damage. This paper provides an overview of recent advances in understanding of the relations between ER stress and brain ischemia. PMID:26289799

  17. Caffeine reduces dipyridamole-induced myocardial ischemia

    SciTech Connect

    Smits, P.; Aengevaeren, W.R.; Corstens, F.H.; Thien, T. )

    1989-10-01

    The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-{sup 201}Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed nodepressions, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging.

  18. Kappa Opioid Receptor Agonist and Brain Ischemia

    PubMed Central

    Chunhua, Chen; Chunhua, Xi; Megumi, Sugita; Renyu, Liu

    2014-01-01

    Opioid receptors, especially Kappa opioid receptor (KOR) play an important role in the pathophysiological process of cerebral ischemia reperfusion injury. Previously accepted KOR agonists activity has included anti-nociception, cardiovascular, anti-pruritic, diuretic, and antitussive effects, while compelling evidence from various ischemic animal models indicate that KOR agonist have neuroprotective effects through various mechanisms. In this review, we aimed to demonstrate the property of KOR agonist and its role in global and focal cerebral ischemia. Based on current preclinical research, the KOR agonists may be useful as a neuroprotective agent. The recent discovery of salvinorin A, highly selective non-opioid KOR agonist, offers a new tool to study the role of KOR in brain HI injury and the protective effects of KOR agonist. The unique pharmacological profile of salvinorin A along with the long history of human usage provides its high candidacy as a potential alternative medication for brain HI injury. PMID:25574482

  19. Spinal Cord Stimulation for Chronic Limb Ischemia

    PubMed Central

    Naoum, Joseph J.; Arbid, Elias J.

    2013-01-01

    The treatment of chronic limb ischemia involves the restoration of pulsatile blood flow to the distal extremity. Some patients cannot be treated with endovascular means or with open surgery; some may have medical comorbidities that render them unfit for surgery, while others may have persistent ischemia or pain even in the face of previous attempts at reperfusion. In spinal cord stimulation (SCS), a device with electrodes is implanted in the epidural space to stimulate sensory fibers. This activates cell-signaling molecules that in turn cause the release of vasodilatory molecules, a decrease in vascular resistance, and relaxation of smooth muscle cells. SCS also suppresses sympathetic vasoconstriction and pain transmission. When patient selection is based on microcirculatory parameters, SCS therapy can significantly improve pain relief, halt the progression of ulcers, and potentially achieve limb salvage. PMID:23805343

  20. Is longer sevoflurane preconditioning neuroprotective in permanent focal cerebral ischemia?

    PubMed

    Qiu, Caiwei; Sheng, Bo; Wang, Shurong; Liu, Jin

    2013-08-15

    Sevoflurane preconditioning has neuroprotective effects in the cerebral ischemia/reperfusion model. However, its influence on permanent cerebral ischemia remains unclear. In the present study, the rats were exposed to sevoflurane for 15, 30, 60, and 120 minutes, followed by induction of permanent cerebral ischemia. Results demonstrated that 30- and 60-minute sevoflurane preconditioning significantly reduced the infarct volume at 24 hours after cerebral ischemia, and 60-minute lurane preconditioning additionally reduced the number of TUNEL- and caspase-3-positive cells in the ischemic penumbra. However, 120-minute sevoflurane preconditioning did not show evident neuroprotective effects. Moreover, 60-minute sevoflurane preconditioning significantly attenuated neurological deficits and infarct volume in rats at 4 days after cerebral ischemia. These findings indicated that 60-minute sevoflurane preconditioning can induce the best neuroprotective effects in rats with permanent cerebral ischemia through the inhibition of apoptosis. PMID:25206521

  1. Renal acid-base metabolism after ischemia.

    PubMed

    Holloway, J C; Phifer, T; Henderson, R; Welbourne, T C

    1986-05-01

    The response of the kidney to ischemia-induced cellular acidosis was followed over the immediate one hr post-ischemia reflow period. Clearance and extraction experiments as well as measurement of cortical intracellular pH (pHi) were performed on Inactin-anesthetized Sprague-Dawley rats. Arteriovenous concentration differences and para-aminohippurate extraction were obtained by cannulating the left renal vein. Base production was monitored as bicarbonate released into the renal vein and urine; net base production was related to the renal handling of glutamine and ammonia as well as to renal oxygen consumption and pHi. After a 15 min control period, the left renal artery was snared for one-half hr followed by release and four consecutive 15 min reflow periods. During the control period, cortical cell pHi measured by [14C]-5,5-Dimethyl-2,4-Oxazolidinedione distribution was 7.07 +/- 0.08, and Q-O2 was 14.1 +/- 2.2 micromoles/min; neither net glutamine utilization nor net bicarbonate generation occurred. After 30 min of ischemia, renal tissue pH fell to 6.6 +/- 0.15. However, within 45 min of reflow, cortical cell pH returned and exceeded the control value, 7.33 +/- 0.06 vs. 7.15 +/- 0.08. This increase in pHi was associated with a significant rise in cellular metabolic rate, Q-O2 increased to 20.3 +/- 6.4 micromoles/min. Corresponding with cellular alkalosis was a net production of bicarbonate and a net ammonia uptake and glutamine release; urinary acidification was abolished. These results are consistent with a nonexcretory renal metabolic base generating mechanism governing cellular acid base homeostasis following ischemia. PMID:3723929

  2. Ischemia, reperfusion and oxygen free radicals.

    PubMed

    Manso, C F

    1992-11-01

    Alterations which occur during ischemia are reviewed. They modify the metabolic status in such a way they prepare the cell to an anomalous response to reoxygenation. The consequence of this disturbance is the generation of oxygen free radicals through several mechanisms, including the mitochondrial oxidative phosphorylation, the arachidonic acid cascade, the activation of xanthine oxidase, activation of phagocytes, iron mobilization, etc. Reduced glutathione is exhausted, proteins are inactivated. Lipid peroxidation induces membrane breakdown and cellular death. PMID:1290647

  3. Urticarial Vasculitis-Associated Intestinal Ischemia

    PubMed Central

    Wong, Uni; Yfantis, Harris; Xie, Guofeng

    2016-01-01

    Urticarial vasculitis (UV) is a rare small vessel vasculitis. UV is often idiopathic but can also present in the context of autoimmune disorders such as systemic lupus erythematosus, drug reactions, infections, or a paraneoplastic syndrome. Extracutaneous complications include intestinal ischemic injuries, in UV patients with nonspecific gastrointestinal symptoms such as abdominal pain and nausea. Prompt recognition and treatment can minimize morbidity and mortality. This paper describes a case of urticarial vasculitis-associated intestinal ischemia. PMID:27190661

  4. Urticarial Vasculitis-Associated Intestinal Ischemia.

    PubMed

    Wong, Uni; Yfantis, Harris; Xie, Guofeng

    2016-01-01

    Urticarial vasculitis (UV) is a rare small vessel vasculitis. UV is often idiopathic but can also present in the context of autoimmune disorders such as systemic lupus erythematosus, drug reactions, infections, or a paraneoplastic syndrome. Extracutaneous complications include intestinal ischemic injuries, in UV patients with nonspecific gastrointestinal symptoms such as abdominal pain and nausea. Prompt recognition and treatment can minimize morbidity and mortality. This paper describes a case of urticarial vasculitis-associated intestinal ischemia. PMID:27190661

  5. [Transition of myocardial ischemia to heart failure].

    PubMed

    Ertl, G; Fraccarollo, D; Gaudron, P; Hu, K; Laser, A; Neubauer, S; Schorb, W

    1998-09-01

    Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed ("stunning"), or persistent if perfusion remains reduced ("hibernation") and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance. PMID:9816648

  6. Polyphenols and neuroprotection against ischemia and neurodegeneration.

    PubMed

    Lin, B

    2011-12-01

    Neuroprotection of polyphenols in medical plants is getting attention in the world. Scutellaria baicalensis, paeonia veitchii and paeonia suffruticosa have been extensively studied in the last 10 years and show multi-function. They are neuroprotectants, antioxidants, anti-inflammatory and antithrombic agents as well as vasoconstriction inhibitors and amyloid-peptide (Aβ) cleaners by means of their polyphenols: baicalin, baicalein, wogonin (in scutellaria), and paeonol, paeonoside, paeoniflorin (PF) and 1, 2, 3, 4, 6-Penta-O-galloyl-beta-D-glucose (PGG) (in paeonia veitchii and paeonia suffruticosa). Other 4 medical plants: astragali, ligusticum wallichii, angelica sinensis and carthamus tinctorius (saffron) have been the major medicines to treat ischemia for hundreds of years in China, Korea and Japan. Our recent experimental studies demonstrated the neuroprotective efficacy of the combination of these phyotmedicines on mitigating brain infarction and global ischemia as well as preventing the neurodegeneration following ischemia. Owing to their multi-function, including improving cerebral blood circulation, they therefore have the potential to alleviate the symptoms of degenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). Pharmacology of the 7 herbs and their major relative polyphenols is depicted in the article. PMID:22070681

  7. Modulation of cardiac metabolism during myocardial ischemia.

    PubMed

    Chagas, Antonio C P; Dourado, Paulo M M; Galvão, Tatiana de Fátima Gonçalves

    2008-01-01

    Metabolic modulation during myocardial ischemia is possible by the use of specific drugs, which may induce a shift from free fatty acid towards predominantly glucose utilization by the myocardium to increase ATP generation per unit oxygen consumption. Three agents (trimetazidine, ranolazine, and perhexiline) have well-documented anti-ischaemic effects. However, perhexiline, the most potent agent currently available, requires plasma-level monitoring to avoid hepato-neuro-toxicity. Besides, the long-term safety of trimetazidine and ranolazine has yet to be established. In addition to their effect in ischemia, the potential use of these drugs in chronic heart failure is gaining recognition as clinical and experimental data are showing the improvement of myocardial function following treatment with several of them, even in the absence of ischemia. Future applications for this line of treatment is promising and deserves additional research. In particular, large, randomised, controlled trials investigating the effects of these agents on mortality and hospitalization rates due to coronary artery disease are needed. PMID:18991673

  8. Traditional Chinese herbal medicine and cerebral ischemia.

    PubMed

    Chen, Yuh-Fung

    2012-01-01

    Stroke is an important cause of mortality and morbidity worldwide but effective therapeutic strategy for the prevention of brain injury in patients with cerebral ischemia is lacking. Although tissue plasminogen activator (t-PA) has been used to treat stroke patients, this therapeutic strategy is confronted with ill side effects and is limited to patients within 3 hours of a stroke. Stroke-mediated cell death is a complex interplay of aberrant events involving excitotoxicity, acidosis, inflammation, oxidative stress, peri-infarct depolarization, and apoptosis. Due to the complexity of the events and the disappointing results from single agent trials, the combination of thrombolytic therapy and effective neural protection therapy may be an alternative strategy for patients with cerebral ischemia. Traditional Chinese herbal medicine has been described in ancient medicine systems as a treatment for various ailments associated with stroke. Recently, there have been reports of its benefits in treating stroke. This review will focus on various traditional Chinese herbal medicines and their neuroprotective effects on cerebral ischemia. PMID:22201915

  9. Multiple molecular penumbras after focal cerebral ischemia.

    PubMed

    Sharp, F R; Lu, A; Tang, Y; Millhorn, D E

    2000-07-01

    Though the ischemic penumbra has been classically described on the basis of blood flow and physiologic parameters, a variety of ischemic penumbras can be described in molecular terms. Apoptosis-related genes induced after focal ischemia may contribute to cell death in the core and the selective cell death adjacent to an infarct. The HSP70 heat shock protein is induced in glia at the edges of an infarct and in neurons often at some distance from the infarct. HSP70 proteins are induced in cells in response to denatured proteins that occur as a result of temporary energy failure. Hypoxia-inducible factor (HIF) is also induced after focal ischemia in regions that can extend beyond the HSP70 induction. The region of HIF induction is proposed to represent the areas of decreased cerebral blood flow and decreased oxygen delivery. Immediate early genes are induced in cortex, hippocampus, thalamus, and other brain regions. These distant changes in gene expression occur because of ischemia-induced spreading depression or depolarization and could contribute to plastic changes in brain after stroke. PMID:10908035

  10. A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia.

    PubMed

    Kaneko, Kazuhiro; Yonemitsu, Yoshikazu; Fujii, Takaaki; Onimaru, Mitsuho; Jin, Chen-Hao; Inoue, Makoto; Hasegawa, Mamoru; Onohara, Toshihiro; Maehara, Yoshihiko; Sueishi, Katsuo

    2006-04-01

    The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed. PMID:16301206

  11. GSK-3β downregulates Nrf2 in cultured cortical neurons and in a rat model of cerebral ischemia-reperfusion

    PubMed Central

    Chen, Xi; Liu, Yuanling; Zhu, Jin; Lei, Shipeng; Dong, Yuan; Li, Lingyu; Jiang, Beibei; Tan, Li; Wu, Jingxian; Yu, Shanshan; Zhao, Yong

    2016-01-01

    The NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway plays a critical role in protecting against oxidative stress in brain ischemia and reperfusion injury. Glycogen synthase kinase 3β (GSK-3β) may play a critical role in regulating Nrf2 in a Kelch-like ECH-associated protein 1 (Keap1)-independent manner. However, the relationship between GSK-3β and Nrf2 in brain ischemia and reperfusion injury is not clear. In this study, we explored the mechanisms through which GSK-3β regulates Nrf2 and Nrf-2/ARE pathways in vitro and in vivo. We used oxygen and glucose deprivation/reoxygenation (OGD/R) in primary cultured cortical neurons and a middle cerebral artery occlusion-reperfusion (MCAO/R) rat model to mimic ischemic insult. In this study, GSK-3β siRNA and inhibitors (SB216763 and LiCl) were used to inhibit GSK-3β in vitro and in vivo. After inhibiting GSK-3β, expression of total and nuclear Nrf2, Nrf2-ARE binding activity, and expression of Nrf2/ARE pathway-driven genes HO-1 and NQO-1 increased. Overexpression of GSK-3β yielded opposite results. These results suggest that GSK-3β downregulates Nrf2 and the Nrf2/ARE pathway in brain ischemia and reperfusion injury. GSK-3β may be an endogenous antioxidant relevant protein, and may represent a new therapeutic target in treatment of ischemia and reperfusion injury. PMID:26838164

  12. Pulmonary leukosequestration induced by hind limb ischemia.

    PubMed Central

    Anner, H; Kaufman, R P; Kobzik, L; Valeri, C R; Shepro, D; Hechtman, H B

    1987-01-01

    Lower torso ischemia leads to acute respiratory failure, an event associated with the accumulation of inflammatory cells in the lungs. This study tests whether ischemia-induced eicosanoid synthesis leads to polymorphonuclear leukocyte (PMN) accumulation in the lungs. Anesthetized rats (N = 51) were randomized into five groups: nonischemic sham rats (N = 10); the remaining four groups were rats made ischemic for 4 hours with bilateral thigh tourniquets treated just before tourniquet release with saline vehicle (N = 17): the thromboxane (Tx) synthase inhibitor OKY-046 (Ono Pharmaceutica, Osaka, Japan) 2 mg/kg intravenously every 2 hours (N = 8); the lipoxygenase inhibitor diethylcarbamazine (DEC) (Sigma, St. Louis, MO) 0.2 mg/kg/min intravenously (N = 8); the platelet-activating factor receptor antagonist SRI (Sandoz Inc., East Hanover, NJ) 63-072 3 mg/kg intravenously every 30 minutes (N = 8). Four hours after ischemia, plasma TxB2 levels in the ischemic placebo-treated group was 3570 +/- 695 pg/mL, compared with 495 +/- 73 pg/mL in sham rats (p less than 0.001). Lung microscopy showed foci of proteinaceous exudate in alveoli and 121 +/- 10 PMN/20 high power fields (HPF) compared with 59 +/- 9 PMN/20 HPF in the sham group (p less than 0.001). One day after ischemia PMN accumulations remained elevated at 119 PMN/20 HPF. Pretreatment with OKY-046 led to reduced TxB2 levels of 149 +/- 17 pg/mL, normal lung histology, and 83 +/- 13 PMN/20 HPF, a value similar to that of the sham group and lower than that of the placebo-treated group (p less than 0.05). Treatment with DEC yielded TxB2 levels of 1419 +/- 492 pg/mL, which was lower than that of the placebo group (p less than 0.05) but higher than that of the sham group (p less than 0.05). Microscopy showed normal lungs with 79 +/- 7 PMN/20 HPF lower than the placebo group (p less than 0.05). SRI 63-072 did not inhibit Tx synthesis or leukosequestration in the lungs. Platelet counts decreased in all groups relative to sham

  13. Using multimodal imaging techniques to monitor limb ischemia: a rapid noninvasive method for assessing extremity wounds

    NASA Astrophysics Data System (ADS)

    Luthra, Rajiv; Caruso, Joseph D.; Radowsky, Jason S.; Rodriguez, Maricela; Forsberg, Jonathan; Elster, Eric A.; Crane, Nicole J.

    2013-03-01

    Over 70% of military casualties resulting from the current conflicts sustain major extremity injuries. Of these the majority are caused by blasts from improvised explosive devices. The resulting injuries include traumatic amputations, open fractures, crush injuries, and acute vascular disruption. Critical tissue ischemia—the point at which ischemic tissues lose the capacity to recover—is therefore a major concern, as lack of blood flow to tissues rapidly leads to tissue deoxygenation and necrosis. If left undetected or unaddressed, a potentially salvageable limb may require more extensive debridement or, more commonly, amputation. Predicting wound outcome during the initial management of blast wounds remains a significant challenge, as wounds continue to "evolve" during the debridement process and our ability to assess wound viability remains subjectively based. Better means of identifying critical ischemia are needed. We developed a swine limb ischemia model in which two imaging modalities were combined to produce an objective and quantitative assessment of wound perfusion and tissue viability. By using 3 Charge-Coupled Device (3CCD) and Infrared (IR) cameras, both surface tissue oxygenation as well as overall limb perfusion could be depicted. We observed a change in mean 3CCD and IR values at peak ischemia and during reperfusion correlate well with clinically observed indicators for limb function and vitality. After correcting for baseline mean R-B values, the 3CCD values correlate with surface tissue oxygenation and the IR values with changes in perfusion. This study aims to not only increase fundamental understanding of the processes involved with limb ischemia and reperfusion, but also to develop tools to monitor overall limb perfusion and tissue oxygenation in a clinical setting. A rapid and objective diagnostic for extent of ischemic damage and overall limb viability could provide surgeons with a more accurate indication of tissue viability. This may

  14. Toward A Mouse Model of Hind Limb Ischemia to Test Therapeutic Angiogenesis

    PubMed Central

    Brenes, Robert A.; Jadlowiec, Caroline C.; Bear, Mackenzie; Hashim, Peter; Protack, Clinton D.; Li, Xin; Lv, Wei; Collins, Michael J.; Dardik, Alan

    2012-01-01

    Introduction Several clinical trials are currently evaluating stem cell therapy for patients with critical limb ischemia that have no other surgical or endovascular options for revascularization. However, these trials are conducted with different protocols, including use of different stem cell populations and different injection protocols, providing little means to compare trials and guide therapy. Accordingly, we developed a murine model of severe ischemia to allow methodical testing of relevant clinical parameters. Methods High femoral artery ligation and total excision of the superficial femoral artery (SFA) was performed on C57BL/6 mice. MNC were isolated from the bone marrow of donor mice, characterized using FACS, and injected (5×105−2×106) into the semimembranosus (proximal) or gastrocnemius (distal) muscle. Vascular and functional outcomes were measured using invasive Doppler, laser Doppler perfusion imaging, and the Tarlov and ischemia scores. Histological analysis included quantification of muscle fiber area and number as well as capillary density. Results Blood flow and functional outcomes were improved in MNC-treated mice as compared to controls over 28 days (Flow: P < .0001; Tarlov: P = .0004; ischemia score: P = .0002). MNC-treated mice also showed greater gastrocnemius fiber area (P = .0053) and increased capillary density (P = .0004). Dose-response analysis showed increased angiogenesis and gastrocnemius fiber area but no changes in macroscopic vascular flow or functional scores. Mice injected proximally to the ischemic area had overall similar functional outcomes to mice injected more distally, but increased muscle flow, capillary density, and gastrocnemius fiber area (P < .05). Conclusions High femoral ligation with complete excision of the SFA is a reliable model of severe hind limb ischemia in C57BL/6 mice that shows a response to MNC-treatment for both functional and vascular outcomes. A dose response to MNC injection appears to be present

  15. Towards a dynamical network view of brain ischemia and reperfusion. Part III: therapeutic implications

    PubMed Central

    DeGracia, Donald J.

    2011-01-01

    The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the “ischemic cascade”. This is the third in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. Here the bistable model of brain ischemia is compared to the ischemic cascade concept. The core weakness of the ischemic cascade concept is revealed to be its assumption of superposition, or that the elements of the ischemic cascade can be summed as linearly independent events. This assumption leads to a concept of neuroprotection as a subtraction of ostensibly independent damage events. The bistable model offers a different concept of neuroprotection where the role of individual molecular pathways decreases in relevance with respect to the efficacy of outcome. Network thinking provides a framework for critical assessment of widely-used preclinical experimental approaches. The importance of allometric scaling is also discussed. We illustrate that the bistable model provides a viable alternative to the ischemic cascade as an explanatory framework and as a guide for therapeutic development. PMID:21278805

  16. Interleukin-1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat.

    PubMed

    Parry-Jones, Adrian R; Liimatainen, Timo; Kauppinen, Risto A; Gröhn, Olli H J; Rothwell, Nancy J

    2008-06-01

    The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 microg/kg IL-1 (n=9) or vehicle (n=10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7 degrees C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion. PMID:18421691

  17. Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon in a neonate of life- and limb-threatening nature: A case report

    PubMed Central

    Subash, Anoop; Senthil, Ganesh K.; Ramamoorthy, Ramkumar; Appasamy, Andal; Selvarajan, Namasivayam

    2015-01-01

    Kaposiform hemangioendothelioma involving whole of a leg in a neonate with Kasabach-Merritt phenomenon causing limb and life-threatening situation has not been reported. One such case and its successful management is presented in this case report. Literature review is made. PMID:26628813

  18. Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon in a neonate of life- and limb-threatening nature: A case report.

    PubMed

    Subash, Anoop; Senthil, Ganesh K; Ramamoorthy, Ramkumar; Appasamy, Andal; Selvarajan, Namasivayam

    2015-01-01

    Kaposiform hemangioendothelioma involving whole of a leg in a neonate with Kasabach-Merritt phenomenon causing limb and life-threatening situation has not been reported. One such case and its successful management is presented in this case report. Literature review is made. PMID:26628813

  19. Myocardial ischemia--association with perioperative cardiac morbidity.

    PubMed Central

    Cunningham, A. J.

    1993-01-01

    The development of ambulatory electrocardiographic recorders and analysers and the application of transesophageal echocardiography in the mid-1980's enabled investigators to quantify and describe the occurrence of silent as well as symptomatic ischemia in the perioperative period. Several technical advances which have recently occurred in ECG monitoring include the use of miniaturized digital computing equipment to store and analyze data. In addition, real time ST-segment analysis has become widely available on multicomponent monitors in both the operating room and intensive care units. The incidence of perioperative myocardial ischemia depends on the patient population, the surgical procedure, and the monitoring technique used. Several studies in the early 1990's have shown that cardiac morbidity in patients undergoing major, noncardiac surgery is best predicted by postoperative myocardial ischemia, rather than tradition preoperative clinical predictors. Long duration postoperative ischemia may be the factor most significantly associated with adverse cardiac outcome. Postoperative pain, physiological and emotional stress may all combine to cause tachycardia, hypertension, increase in cardiac output, and fluid shifts which, in high risk patients, might result in subendocardial ischemia and eventual myocardial infarction. If postoperative myocardial ischemia is the cause of late postoperative myocardial infarction in patients undergoing non-cardiac surgery, then treatment of postoperative myocardial ischemia should reduce morbidity. In addition, reducing pain and stress and avoiding postoperative hypoxemia might prevent postoperative myocardial ischemia and minimize the need for extensive preoperative cardiac evaluation. PMID:7825338

  20. Glibenclamide in Cerebral Ischemia and Stroke

    PubMed Central

    Simard, J. Marc; Sheth, Kevin N.; Kimberly, W. Taylor; Stern, Barney J.; del Zoppo, Gregory J.; Jacobson, Sven; Gerzanich, Volodymyr

    2013-01-01

    The sulfonylurea receptor 1 (Sur1)–transient receptor potential 4 (Trpm4) channel is an important molecular element in focal cerebral ischemia. The channel is upregulated in all cells of the neurovascular unit following ischemia, and is linked to microvascular dysfunction that manifests as edema formation and secondary hemorrhage, which cause brain swelling. Activation of the channel is a major molecular mechanism of cytotoxic edema and “accidental necrotic cell death.” Blockade of Sur1 using glibenclamide has been studied in different types of rat models of stroke: (i) in conventional non-lethal models (thromboembolic, 1–2 h temporary, or permanent middle cerebral artery occlusion), glibenclamide reduces brain swelling and infarct volume and improves neurological function; (ii) in lethal models of malignant cerebral edema, glibenclamide reduces edema, brain swelling, and mortality; (iii) in models with rtPA, glibenclamide reduces swelling, hemorrhagic transformation, and death. Retrospective studies of diabetic patients who present with stroke have shown that those whose diabetes is managed with a sulfonylurea drug and who are maintained on the sulfonylurea drug during hospitalization for stroke have better outcomes at discharge and are less likely to suffer hemorrhagic transformation. Here, we provide a comprehensive review of the basic science, preclinical experiments, and retrospective clinical studies on glibenclamide in focal cerebral ischemia and stroke. We also compare the preclinical work in stroke models to the updated recommendations of the Stroke Therapy Academic Industry Roundtable (STAIR). The findings reviewed here provide a strong foundation for a translational research program to study glibenclamide in patients with ischemic stroke. PMID:24132564

  1. Endovascular Intervention in the Treatment of Peripheral Artery Disease.

    PubMed

    Couto, Marian; Figueróa, Alejandro; Sotolongo, Antonio; Pérez, Reynerio; Ojeda, José Martinez

    2015-01-01

    Endovascular therapy has emerged as an essential part of the management we can offer patients suffering from peripheral arterial disease. The AHA/ACCF guidelines deemed ballon angioplasty as a reasonable alternative for patients with limb threatening lower extremity ischemia who are not candidates for an autologus venous graft. Endovascular treatment is most useful for the treatment of critical limb ischemia and should ensure adequate proximal flow before engaging in interventions of distal disease.To increase procedure success rate, a thorough diagnostic evaluation is fundamental. This evaluation must take into account amount of calcium, no flow occlusion, length of occlusion, and presence of collaterals. There are different tools and procedure techniques available. Among these are the medicated ballon angioplasty and atherectomy by laser or high-speed drill, among others. Further studies may consolidate endovascular intervention as a safe and effective management for patients with lower extremity arterial disease and possibly cause a change in the actual practice guidelines. PMID:26742196

  2. Digital ischemia as a manifestation of malignancy.

    PubMed Central

    Taylor, L M; Hauty, M G; Edwards, J M; Porter, J M

    1987-01-01

    The association of malignancy with thrombotic disorders of the arterial and venous systems is well described. To date, however, there are only 23 published case reports of digital gangrene associated with malignancy. During a prospective evaluation of over 700 patients with finger ischemia, there were five patients with finger gangrene associated with malignancy. Detailed clinical and laboratory evaluation, including detailed immunologic survey and hand angiography, allowed establishment of the precise mechanisms responsible for vascular occlusions in each patient. Three mechanisms were identified: arteritis, hyperviscosity, and hypercoagulability. Digital gangrene associated with malignancy is a rare condition, the mechanism for which can be deduced by careful diagnostic evaluation. Images Fig. 1. PMID:3606232

  3. Repeated early thrombolysis in cervical spinal cord ischemia.

    PubMed

    Etgen, Thorleif; Höcherl, Constanze

    2016-07-01

    Specific therapy of acute spinal ischemia is not established. We report the first case of an MRI-verified cervical spinal ischemia treated by thrombolysis and review the literature. A 72-year old woman with right-sided motor hemiparesis and trunk ataxia was treated by intravenous thrombolysis with full recovery. Three days later she developed again a severe right-sided sensorimotor hemiparesis and a second off-label intravenous thrombolysis was repeated. Magnetic resonance imaging revealed a right-sided posterior-lateral cervical spinal ischemia. Spinal ischemia may clinically present with a cerebral-stroke-like picture challenging diagnostic and therapeutic procedure. Systemic thrombolysis might be a treatment option in acute spinal ischemia. In addition, early repeated systemic thrombolysis may be considered in selected strokes. PMID:26762860

  4. Enteral nutrition associated non-occlusive bowel ischemia

    PubMed Central

    Gwon, Jun-Gyo; Lee, Young-Ju; Kyoung, Kyu-Hyouck; Kim, Young-Hwan

    2012-01-01

    We describe two patients, with no previous history of vascular problems but poor lung function, who experienced septic shock due to bowel ischemia. Both were fed an enteral formula rich in fiber using a feeding tube and experienced septic shock with regular enteral feeding. Surgical finding showed hemorrhagic ischemia in the bowel. The pathologic finding suggests these changes may have been due to inspissations of bowel contents, which may put direct pressure on the mucosa of the bowel wall, leading to local impairment of mucosal and submucosal blood flow with subsequent bowel necrosis. Bowel ischemia may have been precipitated by an increased mesenteric blood flow requirement in combination with a metabolically stressed bowel. Patients in the intensive care unit fed a fiber-rich enteral formula may have inspissated bowel contents, leading to bowel ischemia, suggesting that the use of fiber-rich formula should be limited in patients at high-risk of bowel ischemia. PMID:22977764

  5. Enteral nutrition associated non-occlusive bowel ischemia.

    PubMed

    Gwon, Jun-Gyo; Lee, Young-Ju; Kyoung, Kyu-Hyouck; Kim, Young-Hwan; Hong, Suk-Kyung

    2012-09-01

    We describe two patients, with no previous history of vascular problems but poor lung function, who experienced septic shock due to bowel ischemia. Both were fed an enteral formula rich in fiber using a feeding tube and experienced septic shock with regular enteral feeding. Surgical finding showed hemorrhagic ischemia in the bowel. The pathologic finding suggests these changes may have been due to inspissations of bowel contents, which may put direct pressure on the mucosa of the bowel wall, leading to local impairment of mucosal and submucosal blood flow with subsequent bowel necrosis. Bowel ischemia may have been precipitated by an increased mesenteric blood flow requirement in combination with a metabolically stressed bowel. Patients in the intensive care unit fed a fiber-rich enteral formula may have inspissated bowel contents, leading to bowel ischemia, suggesting that the use of fiber-rich formula should be limited in patients at high-risk of bowel ischemia. PMID:22977764

  6. Mangafodipir Protects against Hepatic Ischemia-Reperfusion Injury in Mice

    PubMed Central

    Coriat, Romain; Leconte, Mahaut; Kavian, Niloufar; Bedda, Sassia; Nicco, Carole; Chereau, Christiane; Goulvestre, Claire; Weill, Bernard

    2011-01-01

    Introduction and Aim Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. Methods Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. Results Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. Conclusions Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury. PMID:22073237

  7. Procaspase-9 induces its cleavage by transnitrosylating XIAP via the Thioredoxin system during cerebral ischemia-reperfusion in rats

    PubMed Central

    Zhang, Dengyue; Zhao, Ningjun; Ma, Bin; Wang, Yan; Zhang, Gongliang; Yan, Xianliang; Hu, Shuqun; Xu, Tie

    2016-01-01

    Transnitrosylation is an important mechanism by which nitric oxide (NO) modulates cell signaling pathways. For instance, SNO-caspase-3 can transnitrosylate the X-linked inhibitor of apoptosis (XIAP) to enhance apoptosis. XIAP is a potent antagonist of caspase apoptotic activity. Decrease in XIAP activity via nitrosylation results in SNO-XIAP-mediated caspase activation. Considering the functional liaison of procaspase-9 and XIAP, we hypothesized that procaspase-9 nitrosylates XIAP directly. Our data confirmed that cerebral ischemia-reperfusion induced XIAP nitrosylation, procaspase-9 denitrosylation and cleavage. Interestingly, the time courses of the nitrosylation of procaspase-9 and XIAP were negatively correlated, which was more prominent after cerebral ischemia-reperfusion, suggesting a direct interaction. The nitrosylation of XIAP, as well as the denitrosylation and cleavage of procaspase-9, were inhibited by DNCB, TrxR1 AS-ODNs, or TAT-AVPY treatment. Meanwhile, DNCB, TrxR1 AS-ODNs, or TAT-AVPY also inhibited the decrease in hippocampal CA1 neurons induced by ischemia-reperfusion in rats. The denitrosylation and cleavage of procaspase-9 induced by OGD/reoxygenation in SH-SY5Y cells were inhibited when cells were co-transfected with wild-type procaspase-9 and XIAP mutant (C449G). These data suggest that cerebral ischemia-reperfusion induces a transnitrosylation from procaspase-9 to XIAP via the Trx system to consequently cause apoptosis. Additionally, Cys325 is a critical S-nitrosylation site of procaspase-9. PMID:27052476

  8. Procaspase-9 induces its cleavage by transnitrosylating XIAP via the Thioredoxin system during cerebral ischemia-reperfusion in rats.

    PubMed

    Zhang, Dengyue; Zhao, Ningjun; Ma, Bin; Wang, Yan; Zhang, Gongliang; Yan, Xianliang; Hu, Shuqun; Xu, Tie

    2016-01-01

    Transnitrosylation is an important mechanism by which nitric oxide (NO) modulates cell signaling pathways. For instance, SNO-caspase-3 can transnitrosylate the X-linked inhibitor of apoptosis (XIAP) to enhance apoptosis. XIAP is a potent antagonist of caspase apoptotic activity. Decrease in XIAP activity via nitrosylation results in SNO-XIAP-mediated caspase activation. Considering the functional liaison of procaspase-9 and XIAP, we hypothesized that procaspase-9 nitrosylates XIAP directly. Our data confirmed that cerebral ischemia-reperfusion induced XIAP nitrosylation, procaspase-9 denitrosylation and cleavage. Interestingly, the time courses of the nitrosylation of procaspase-9 and XIAP were negatively correlated, which was more prominent after cerebral ischemia-reperfusion, suggesting a direct interaction. The nitrosylation of XIAP, as well as the denitrosylation and cleavage of procaspase-9, were inhibited by DNCB, TrxR1 AS-ODNs, or TAT-AVPY treatment. Meanwhile, DNCB, TrxR1 AS-ODNs, or TAT-AVPY also inhibited the decrease in hippocampal CA1 neurons induced by ischemia-reperfusion in rats. The denitrosylation and cleavage of procaspase-9 induced by OGD/reoxygenation in SH-SY5Y cells were inhibited when cells were co-transfected with wild-type procaspase-9 and XIAP mutant (C449G). These data suggest that cerebral ischemia-reperfusion induces a transnitrosylation from procaspase-9 to XIAP via the Trx system to consequently cause apoptosis. Additionally, Cys325 is a critical S-nitrosylation site of procaspase-9. PMID:27052476

  9. Standards and pitfalls of focal ischemia models in spontaneously hypertensive rats: With a systematic review of recent articles

    PubMed Central

    2012-01-01

    We reviewed the early development of various focal ischemia models in spontaneously hypertensive rats (SHR), and summarized recent reports on this topic. Among 6 focal ischemia models established in divergent substrains of SHR, distal middle cerebral artery occlusion is the most frequently used and relevant method of focal ischemia in the light of penumbra concept. We performed an online PubMed search (2001–2010), and identified 118 original articles with focal ischemia in SHR. Physiological parameters such as age, body weight, and even blood pressure were often neglected in the literature: the information regarding the physiological parameters of SHR is critical, and should be provided within the methodology section of all articles related to stroke models in SHR. Although the quality of recent studies on neuroprotective strategy is improving, the mechanisms underlying the protection should be more clearly recognized so as to facilitate the translation from animal studies to human stroke. To overcome the genetic heterogeneity in substrains of SHR, new approaches, such as a huge repository of genetic markers in rat strains and the congenic strategy, are currently in progress. PMID:22770528

  10. Focal embolic cerebral ischemia in the rat

    PubMed Central

    Zhang, Li; Zhang, Rui Lan; Jiang, Quan; Ding, Guangliang; Chopp, Michael; Zhang, Zheng Gang

    2015-01-01

    Animal models of focal cerebral ischemia are well accepted for investigating the pathogenesis and potential treatment strategies for human stroke. Occlusion of the middle cerebral artery (MCA) with an endovascular filament is a widely used model to induce focal cerebral ischemia. However, this model is not amenable to thrombolytic therapies. As thrombolysis with recombinant tissue plasminogen activator (rtPA) is a standard of care within 4.5 hours of human stroke onset, suitable animal models that mimic cellular and molecular mechanisms of thrombosis and thrombolysis of stroke are required. By occluding the MCA with a fibrin-rich allogeneic clot, we have developed an embolic model of MCA occlusion in the rat, which recapitulates the key components of thrombotic development and of thrombolytic therapy of rtPA observed from human ischemic stroke. The surgical procedures of our model can be typically completed within approximately 30 min and are highly adaptable to other strains of rats as well as mice for both genders. Thus, this model provides a powerful tool for translational stroke research. PMID:25741989

  11. Effects of carbon monoxide on myocardial ischemia

    SciTech Connect

    Allred, E.N.; Pagano, M. ); Bleecker, E.R.; Walden, S.M. ); Chaitman, B.R.; Dahms, T.E. ); Hackney, J.D.; Selvester, R.H. ); Warren, J. ); Gottlieb, S.O.

    1991-02-01

    The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre-versus postexposure exercise test at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease.

  12. Effects of cerebral ischemia on neuronal hemoglobin

    PubMed Central

    He, Yangdong; Hua, Ya; Liu, Wenquan; Hu, Haitao; Keep, Richard F.; Xi, Guohua

    2009-01-01

    Summary The present study examined whether or not neuronal hemoglobin (Hb) is present in rats. It then examined whether cerebral ischemia or ischemic preconditioning (IPC) affects neuronal Hb levels in vivo and in vitro. In vivo, male Sprague-Dawley rats were subjected to either 15 minutes of transient middle cerebral artery occlusion with 24 hours of reperfusion, an IPC stimulus, or 24 hours of permanent middle cerebral artery occlusion (pMCAO), or IPC followed three days later by 24 hours of pMCAO. In vitro, primary cultured neurons were exposed to 2 hours of oxygen-glucose deprivation with 22 hours of reoxygenation. Results showed that Hb is widely expressed in rat cerebral neurons but not astrocytes. Hb expression was significantly upregulated in the ipsilateral caudate and the cortical core of the middle cerebral artery territory after IPC. Hb levels also increased in more penumbral cortex and the contralateral hemisphere 24 hours after pMCAO, but expression in the ipsilateral caudate and cortical core area were decreased. Ischemic preconditioning modified pMCAO-induced brain Hb changes. Neuronal Hb levels in vitro were increased by 2 hours of oxygen-glucose deprivation and 22 hours of reoxygenation. These results indicate that Hb is synthesized in neurons and can be upregulated by ischemia. PMID:19066615

  13. Ischemia detection from morphological QRS angle changes.

    PubMed

    Romero, Daniel; Martínez, Juan Pablo; Laguna, Pablo; Pueyo, Esther

    2016-07-01

    In this paper, an ischemia detector is presented based on the analysis of QRS-derived angles. The detector has been developed by modeling ischemic effects on the QRS angles as a gradual change with a certain transition time and assuming a Laplacian additive modeling error contaminating the angle series. Both standard and non-standard leads were used for analysis. Non-standard leads were obtained by applying the PCA technique over specific lead subsets to represent different potential locations of the ischemic zone. The performance of the proposed detector was tested over a population of 79 patients undergoing percutaneous coronary intervention in one of the major coronary arteries (LAD (n  =  25), RCA (n  =  16) and LCX (n  =  38)). The best detection performance, obtained for standard ECG leads, was achieved in the LAD group with values of sensitivity and specificity of [Formula: see text], [Formula: see text], followed by the RCA group with [Formula: see text], Sp  =  94.4 and the LCX group with [Formula: see text], [Formula: see text], notably outperforming detection based on the ST series in all cases, with the same detector structure. The timing of the detected ischemic events ranged from 30 s up to 150 s (mean  =  66.8 s) following the start of occlusion. We conclude that changes in the QRS angles can be used to detect acute myocardial ischemia. PMID:27243441

  14. Understanding STAT3 signaling in cardiac ischemia.

    PubMed

    O'Sullivan, K E; Breen, E P; Gallagher, H C; Buggy, D J; Hurley, J P

    2016-05-01

    Cardiovascular disease is the leading cause of death worldwide. It remains one of the greatest challenges to global health and will continue to dominate mortality trends in the future. Acute myocardial infarction results in 7.4 million deaths globally per annum. Current management strategies are centered on restoration of coronary blood flow via percutaneous coronary intervention, coronary artery bypass grafting and administration of anti-platelet agents. Such myocardial reperfusion accounts for 40-50 % of the final infarct size in most cases. Signaling transducer and activator of transcription 3 (STAT3) has been shown to have cardioprotective effects via canonical and non-canonical activation and modulation of mitochondrial and transcriptional responses. A significant body of in vitro and in vivo evidence suggests that activation of the STAT3 signal transduction pathway results in a cardio protective response to ischemia and attempts have been made to modulate this with therapeutic effect. Not only is STAT3 important for cardiomyocyte function, but it also modulates the cardiac microenvironment and communicates with cardiac fibroblasts. To this end, we here review the current evidence supporting the manipulation of STAT3 for therapeutic benefit in cardiac ischemia and identify areas for future research. PMID:27017613

  15. Effective treatment of vascular endothelial growth factor refractory hindlimb ischemia by a mutant endothelial nitric oxide synthase gene.

    PubMed

    Qian, H S; Liu, P; Huw, L-Y; Orme, A; Halks-Miller, M; Hill, S M; Jin, F; Kretschmer, P; Blasko, E; Cashion, L; Szymanski, P; Vergona, R; Harkins, R; Yu, J; Sessa, W C; Dole, W P; Rubanyi, G M; Kauser, K

    2006-09-01

    Gene delivery of angiogenic growth factors is a promising approach for the treatment of ischemic cardiovascular diseases. However, success of this new therapeutic principle is hindered by the lack of critical understanding as to how disease pathology affects the efficiency of gene delivery and/or the downstream signaling pathways of angiogenesis. Critical limb ischemia occurs in patients with advanced atherosclerosis often exhibiting deficiency in endothelial nitric oxide production. Similar to these patients, segmental femoral artery resection progresses into severe ischemic necrosis in mice deficient in endothelial nitric oxide synthase (ecNOS-KO) as well as in balb/c mice. We used these models to evaluate the influence of severe ischemia on transfection efficiency and duration of transgene expression in the skeletal muscle following plasmid injection in combination with electroporation. Subsequently, we also explored the potential therapeutic effect of the phosphomimetic mutant of ecNOS gene (NOS1177D) using optimized delivery parameters, and found significant benefit both in ecNOS-KO and balb/c mice. Our results indicate that NOS1177D gene delivery to the ischemic skeletal muscle can be efficient to reverse critical limb ischemia in pathological settings, which are refractory to treatments with a single growth factor, such as vascular endothelial growth factor. PMID:16642030

  16. Blue light reduces organ injury from ischemia and reperfusion

    PubMed Central

    Yuan, Du; Collage, Richard D.; Huang, Hai; Zhang, Xianghong; Kautza, Benjamin C.; Lewis, Anthony J.; Zuckerbraun, Brian S.; Tsung, Allan; Angus, Derek C.; Rosengart, Matthew R.

    2016-01-01

    Evidence suggests that light and circadian rhythms profoundly influence the physiologic capacity with which an organism responds to stress. However, the ramifications of light spectrum on the course of critical illness remain to be determined. Here, we show that acute exposure to bright blue spectrum light reduces organ injury by comparison with bright red spectrum or ambient white fluorescent light in two murine models of sterile insult: warm liver ischemia/reperfusion (I/R) and unilateral renal I/R. Exposure to bright blue light before I/R reduced hepatocellular injury and necrosis and reduced acute kidney injury and necrosis. In both models, blue light reduced neutrophil influx, as evidenced by reduced myeloperoxidase (MPO) within each organ, and reduced the release of high-mobility group box 1 (HMGB1), a neutrophil chemotactant and key mediator in the pathogenesis of I/R injury. The protective mechanism appeared to involve an optic pathway and was mediated, in part, by a sympathetic (β3 adrenergic) pathway that functioned independent of significant alterations in melatonin or corticosterone concentrations to regulate neutrophil recruitment. These data suggest that modifying the spectrum of light may offer therapeutic utility in sterile forms of cellular injury. PMID:27114521

  17. An Evidence-Based Review of Related Metabolites and Metabolic Network Research on Cerebral Ischemia

    PubMed Central

    Liu, Mengting; Tang, Liying; Liu, Xin; Fang, Jing; Zhan, Hao; Wu, Hongwei; Yang, Hongjun

    2016-01-01

    In recent years, metabolomics analyses have been widely applied to cerebral ischemia research. This paper introduces the latest proceedings of metabolomics research on cerebral ischemia. The main techniques, models, animals, and biomarkers of cerebral ischemia will be discussed. With analysis help from the MBRole website and the KEGG database, the altered metabolites in rat cerebral ischemia were used for metabolic pathway enrichment analyses. Our results identify the main metabolic pathways that are related to cerebral ischemia and further construct a metabolic network. These results will provide useful information for elucidating the pathogenesis of cerebral ischemia, as well as the discovery of cerebral ischemia biomarkers. PMID:27274780

  18. mRNA redistribution during permanent focal cerebral ischemia.

    PubMed

    Lewis, Monique K; Jamison, Jill T; Dunbar, Joseph C; DeGracia, Donald J

    2013-12-01

    Translation arrest occurs in neurons following focal cerebral ischemia and is irreversible in penumbral neurons destined to die. Following global cerebral ischemia, mRNA is sequestered away from 40S ribosomal subunits as mRNA granules, precluding translation. Here, we investigated mRNA granule formation using fluorescence in situ histochemistry out to 8 h permanent focal cerebral ischemia using middle cerebral artery occlusion in Long Evans rats with and without diabetes. Neuronal mRNA granules colocalized with PABP, HuR, and NeuN, but not 40S or 60S ribosomal subunits, or organelle markers. The volume of brain with mRNA granule-containing neurons decreased exponentially with ischemia duration, and was zero after 8 h permanent focal cerebral ischemia or any duration of ischemia in diabetic rats. These results show that neuronal mRNA granule response has a limited range of insult intensity over which it is expressed. Identifying the limits of effective neuronal stress response to ischemia will be important for developing effective stroke therapies. PMID:24323415

  19. Amino Acids as Metabolic Substrates during Cardiac Ischemia

    PubMed Central

    Drake, Kenneth J.; Sidorov, Veniamin Y.; McGuinness, Owen P.; Wasserman, David H.; Wikswo, John P.

    2013-01-01

    The heart is well known as a metabolic omnivore in that it is capable of consuming fatty acids, glucose, ketone bodies, pyruvate, lactate, amino acids and even its own constituent proteins, in order of decreasing preference. The energy from these substrates supports not only mechanical contraction, but also the various transmembrane pumps and transporters required for ionic homeostasis, electrical activity, metabolism and catabolism. Cardiac ischemia – for example, due to compromise of the coronary vasculature or end-stage heart failure – will alter both electrical and metabolic activity. While the effects of myocardial ischemia on electrical propagation and stability have been studied in depth, the effects of ischemia on metabolic substrate preference has not been fully appreciated: oxygen deprivation during ischemia will significantly alter the relative ability of the heart to utilize each of these substrates. Although changes in cardiac metabolism are understood to be an underlying component in almost all cardiac myopathies, the potential contribution of amino acids in maintaining cardiac electrical conductance and stability during ischemia is underappreciated. Despite clear evidence that amino acids exert cardioprotective effects in ischemia and other cardiac disorders, their role in the metabolism of the ischemic heart has yet to be fully elucidated. This review synthesizes the current literature of the metabolic contribution of amino acids during ischemia by analyzing relevant historical and recent research. PMID:23354395

  20. Panretinal photocoagulation for radiation-induced ocular ischemia

    SciTech Connect

    Augsburger, J.J.; Roth, S.E.; Magargal, L.E.; Shields, J.A.

    1987-08-01

    We present preliminary findings on the effectiveness of panretinal photocoagulation in preventing neovascular glaucoma in eyes with radiation-induced ocular ischemia. Our study group consisted of 20 patients who developed radiation-induced ocular ischemia following cobalt-60 plaque radiotherapy for a choroidal or ciliary body melanoma. Eleven of the 20 patients were treated by panretinal photocoagulation shortly after the diagnosis of ocular ischemia, but nine patients were left untreated. In this non-randomized study, the rate of development of neovascular glaucoma was significantly lower (p = 0.024) for the 11 photocoagulated patients than for the nine who were left untreated.

  1. Arterial surgery for arm ischemia. A survey of 136 patients.

    PubMed Central

    Holleman, J H; Hardy, J D; Williamson, J W; Raju, S; Neely, W A

    1980-01-01

    A series of 136 patients with upper extremity ischemia requiring operative correction is presented. Causes of the ischemia included trauma, atherosclerosis, embolism, iatrogenic causes, radiation injury, and cervical rib syndrome. Operations included primary repair, various bypass grafts and embolectomy. Illustrative case reports are used to emphasize important points. The subclavian, axillary and brachial arteries have been considered separately. In general, ischemia of the arm caused by a discrete lesion is amenable to surgical correction with an excellent change of success. Images Fig. 1. Figs. 5a and b. Fig. 7. Fig. 8. Fig. 9. PMID:7387235

  2. Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia.

    PubMed

    Kuzuya, T; Hoshida, S; Yamashita, N; Fuji, H; Oe, H; Hori, M; Kamada, T; Tada, M

    1993-06-01

    The infarct-limiting effect of ischemic preconditioning is believed to be a transient phenomenon. We examined the delayed effects of repetitive brief ischemia on limiting infarct size in an open-chest dog model by an occlusion (90 minutes) of the left anterior descending coronary artery (LAD) followed by reperfusion (5 hours). The dogs were preconditioned with four brief repeated ischemic episodes induced by 5-minute LAD occlusions with subsequent reperfusion. The size of infarcts initiated by a sustained occlusion immediately or 24 hours after preconditioning was significantly smaller when compared with infarcts in sham-operated dogs (for the immediate occlusion, 14.4 +/- 2.0% versus 39.0 +/- 3.7%, respectively [p < 0.01]; and for the delayed occlusion, 18.8 +/- 3.4% versus 35.1 +/- 4.6%, respectively [p < 0.05]); however, when the infarction was induced 3 hours (31.2 +/- 3.7% versus 37.5 +/- 4.2%, respectively) or 12 hours (25.4 +/- 4.8% versus 35.0 +/- 5.3%, respectively) after repetitive ischemia, the infarct size did not differ. No differences were seen in regional myocardial blood flow or rate-pressure products between the two groups. These results indicate that an infarct-limiting effect of brief repeated ischemia can be observed 24 hours after sublethal preconditioning. PMID:8495557

  3. Succinate Accumulation and Ischemia-Reperfusion Injury: Of Mice but Not Men, a Study in Renal Ischemia-Reperfusion.

    PubMed

    Wijermars, L G M; Schaapherder, A F; Kostidis, S; Wüst, R C I; Lindeman, J H

    2016-09-01

    A recent seminal paper implicated ischemia-related succinate accumulation followed by succinate-driven reactive oxygen species formation as a key driver of ischemia-reperfusion injury. Although the data show that the mechanism is universal for all organs tested (kidney, liver, heart, and brain), a remaining question is to what extent these observations in mice translate to humans. We showed in this study that succinate accumulation is not a universal event during ischemia and does not occur during renal graft procurement; in fact, tissue succinate content progressively decreased with increasing graft ischemia time (p < 0.007). Contrasting responses were also found with respect to mitochondrial susceptibility toward ischemia and reperfusion, with rodent mitochondria robustly resistant toward warm ischemia but human and pig mitochondria highly susceptible to warm ischemia (p < 0.05). These observations suggest that succinate-driven reactive oxygen formation does not occur in the context of kidney transplantation. Moreover, absent allantoin release from the reperfused grafts suggests minimal oxidative stress during clinical reperfusion. PMID:26999803

  4. Real-Time Visualization of Tissue Ischemia

    NASA Technical Reports Server (NTRS)

    Bearman, Gregory H. (Inventor); Chrien, Thomas D. (Inventor); Eastwood, Michael L. (Inventor)

    2000-01-01

    A real-time display of tissue ischemia which comprises three CCD video cameras, each with a narrow bandwidth filter at the correct wavelength is discussed. The cameras simultaneously view an area of tissue suspected of having ischemic areas through beamsplitters. The output from each camera is adjusted to give the correct signal intensity for combining with, the others into an image for display. If necessary a digital signal processor (DSP) can implement algorithms for image enhancement prior to display. Current DSP engines are fast enough to give real-time display. Measurement at three, wavelengths, combined into a real-time Red-Green-Blue (RGB) video display with a digital signal processing (DSP) board to implement image algorithms, provides direct visualization of ischemic areas.

  5. Vitreal Ocygenation in Retinal Ischemia Reperfusion

    SciTech Connect

    Abdallab, Walid; AmeriMD, Hossein; Barron, Ernesto; ChaderPhD, Gerald; Greenbaum, Elias; Hinton, David E; Humayun, Mark S

    2011-01-01

    PURPOSE. To study the feasibility of anterior vitreal oxygenation for the treatment of acute retinal ischemia. METHODS. Twenty rabbits were randomized into an oxygenation group, a sham treatment group, and a no treatment group. Baseline electroretinography (ERG) and preretinal oxygen (PO2) measurements were obtained 3 to 5 days before surgery. Intraocular pressure was raised to 100 mm Hg for 90 minutes and then normalized. The oxygenation group underwent vitreal oxygenation for 30 minutes using intravitreal electrodes. The sham treatment group received inactive electrodes for 30 minutes while there was no intervention for the no treatment group. Preretinal PO2 in the posterior vitreous was measured 30 minutes after intervention or 30 minutes after reperfusion (no treatment group) and on postoperative days (d) 3, 6, 9, and 12. On d14, rabbits underwent ERG and were euthanatized.

  6. Lymphocytes and ischemia-reperfusion injury.

    PubMed

    Linfert, Douglas; Chowdhry, Tayseer; Rabb, Hamid

    2009-01-01

    Ischemia reperfusion injury (IRI) is a common and important clinical problem in many different organ systems, including kidney, brain, heart, liver, lung, and intestine. IRI occurs during all deceased donor organ transplants. IRI is a highly complex cascade of events that includes interactions between vascular endothelium, interstitial compartments, circulating cells, and numerous biochemical entities. It is well established that the innate immune system, such as complement, neutrophils, cytokines, chemokines, and macrophages participate in IRI. Recent data demonstrates an important role for lymphocytes, particularly T cells but also B cells in IRI. Lymphocytes not only participate in augmenting injury responses after IRI, but could also be playing a protective role depending on the cell type and stage of injury. Furthermore, lymphocytes appear to be participating in the healing response from IRI. These new data open the possibility for lymphocyte targeted therapeutics to improve the short and long term outcomes from IRI. PMID:19027612

  7. Cell Biology of Ischemia/Reperfusion Injury

    PubMed Central

    Kalogeris, Theodore; Baines, Christopher P.; Krenz, Maike; Korthuis, Ronald J.

    2014-01-01

    Disorders characterized by ischemia/reperfusion (I/R), such as myocardial infarction, stroke, and peripheral vascular disease, continue to be among the most frequent causes of debilitating disease and death. Tissue injury and/or death occur as a result of the initial ischemic insult, which is determined primarily by the magnitude and duration of the interruption in the blood supply, and then subsequent damage induced by reperfusion. During prolonged ischemia, ATP levels and intracellular pH decrease as a result of anaerobic metabolism and lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms become dysfunctional, contributing to increased intracellular and mitochondrial calcium levels (calcium overload), cell swelling and rupture, and cell death by necrotic, necroptotic, apoptotic, and autophagic mechanisms. Although oxygen levels are restored upon reperfusion, a surge in the generation of reactive oxygen species occurs and proinflammatory neutrophils infiltrate ischemic tissues to exacerbate ischemic injury. The pathologic events induced by I/R orchestrate the opening of the mitochondrial permeability transition pore, which appears to represent a common end-effector of the pathologic events initiated by I/R. The aim of this treatise is to provide a comprehensive review of the mechanisms underlying the development of I/R injury, from which it should be apparent that a combination of molecular and cellular approaches targeting multiple pathologic processes to limit the extent of I/R injury must be adopted to enhance resistance to cell death and increase regenerative capacity in order to effect long-lasting repair of ischemic tissues. PMID:22878108

  8. Critical Thinking.

    ERIC Educational Resources Information Center

    Callison, Daniel

    1998-01-01

    Distinguishes between critical and creative thinking and discusses critical-thinking in relation to modern instructional programs and information literacy. Outlines goals in critical-thinking curriculum, critical thinking skills (student disposition, interpretation, analysis, evaluation, inference, presenting argument, and reflection), and…

  9. Spinal cord ischemia is multifactorial: what is the best protocol?

    PubMed

    Melissano, Germano; Bertoglio, Luca; Mascia, Daniele; Rinaldi, Enrico; Del Carro, Ubaldo; Nardelli, Pasquale; Chiesa, Roberto

    2016-04-01

    Despite the improved understanding of spinal cord anatomy and spinal cord ischemia pathophysiology, the rate of debilitating postoperative paraparesis or paraplegia is still not negligible after procedures for thoracic or thoracoabdominal aortic disease. Single studies have demonstrated the role of different treatment modalities to prevent or treat spinal cord ischemia. A multimodal approach, however, is advocated by most authors. Even after the employment of endovascular techniques become routine, the rate of spinal cord ischemia after treatment of thoracoabdominal aortic pathology remained unchanged over time. Spinal cord ischemia is often treatable by different means that concur to improve indirect spinal perfusion through collateral circulation; it should, therefore, be managed promptly and aggressively due to its potential reversibility. Ongoing technical improvements of non-invasive diagnostic tools may allow a better preoperative assessment of the spinal vascular network and a better planning of both open and endovascular thoracic or thoracoabdominal repair. PMID:26731537

  10. Hippocampal neurogenesis in the new model of global cerebral ischemia

    NASA Astrophysics Data System (ADS)

    Kisel, A. A.; Chernysheva, G. A.; Smol'yakova, V. I.; Savchenko, R. R.; Plotnikov, M. B.; Khodanovich, M. Yu.

    2015-11-01

    The study aimed to evaluate the changes of hippocampal neurogenesis in a new model of global transient cerebral ischemia which was performed by the occlusion of the three main vessels (tr. brachiocephalicus, a. subclavia sinistra, and a. carotis communis sinistra) branching from the aortic arch and supplying the brain. Global transitory cerebral ischemia was modeled on male rats (weight = 250-300 g) under chloral hydrate with artificial lung ventilation. Animals after the same surgical operation without vessel occlusion served as sham-operated controls. The number of DCX-positive (doublecortin, the marker of immature neurons) cells in dentate gyrus (DG) and CA1-CA3 fields of hippocampus was counted at the 31st day after ischemia modeling. It was revealed that global cerebral ischemia decreased neurogenesis in dentate gyrus in comparison with the sham-operated group (P<0.05) while neurogenesis in CA1-CA3 fields was increased as compared to the control (P<0.05).

  11. Multiple coronary arterial loops as a cause of myocardial ischemia

    NASA Technical Reports Server (NTRS)

    Bashour, Tali T.; Mansour, Nagi N.; Lee, Damon

    1993-01-01

    A case of long-standing angina with ischemia documented by exercise testing and thallium scintigraphy in a patient who had multiple proximal loops in all three major coronary arteries in the absence of luminal stenosis, is reported.

  12. Acute upper limb ischemia, a rare presentation of giant cell arteritis.

    PubMed

    Almeida-Morais, Luís; Galego, Sofia; Marques, Nélia; Pack, Tiago; Rodrigues, Hugo; Abreu, Rodolfo; Vasconcelos, Leonor; Marques, Hugo; Sousa Guerreiro, António

    2016-04-01

    Giant cell arteritis (GCA) is a systemic large vessel vasculitis, with extracranial arterial involvement described in 10-15% of cases, usually affecting the aorta and its branches. Patients with GCA are more likely to develop aortic aneurysms, but these are rarely present at the time of the diagnosis. We report the case of an 80-year-old Caucasian woman, who reported proximal muscle pain in the arms with morning stiffness of the shoulders for eight months. In the previous two months, she had developed worsening bilateral arm claudication, severe pain, cold extremities and digital necrosis. She had no palpable radial pulses and no measurable blood pressure. The patient had normochromic anemia, erythrocyte sedimentation rate of 120 mm/h, and a negative infectious and autoimmune workup. Computed tomography angiography revealed concentric wall thickening of the aorta extending to the aortic arch branches, particularly the subclavian and axillary arteries, which were severely stenotic, with areas of bilateral occlusion and an aneurysm of the ascending aorta (47 mm). Despite corticosteroid therapy there was progression to acute critical ischemia. She accordingly underwent surgical revascularization using a bilateral carotid-humeral bypass. After surgery, corticosteroid therapy was maintained and at six-month follow-up she was clinically stable with reduced inflammatory markers. GCA, usually a chronic benign vasculitis, presented exceptionally in this case as acute critical upper limb ischemia, resulting from a massive inflammatory process of the subclavian and axillary arteries, treated with salvage surgical revascularization. PMID:27006059

  13. Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion

    PubMed Central

    Aşcı, Sanem; Demirci, Serpil; Aşcı, Halil; Doğuç, Duygu Kumbul; Onaran, İbrahim

    2016-01-01

    Background: Stroke is one of the most common causes of death and the leading cause of disability in adults. Cerebral ischemia/reperfusion injury causes cerebral edema, hemorrhage, and neuronal death. Aims: In post-ischemic reperfusion, free radical production causes brain tissue damage by oxidative stress. Pregabalin, an antiepileptic agent was shown to have antioxidant effects. The aim of this study was to evaluate the neuroprotective and antioxidant effects of pregabalin on ischemia and reperfusion in rat brain injury. Study Design: Animal experimentation. Methods: Male Wistar rats weighing (250–300 g) were randomly divided into six groups, each consisting of 6 rats: control (C), pregabalin (P), ischemia (I), pregabalin + ischemia (PI), ischemia + reperfusion (IR) and ischemia + reperfusion + pregabalin (PIR). Rats were initially pre-treated with 50 mg/kg/d pregabalin orally for two days. Then, animals that applied ischemia in I, PI, IR and PIR groups were exposed to carotid clamping for 30 minutes and 20 minutes reperfusion was performed in the relevant reperfusion groups. Results: NR2B receptor levels were significantly lower in the PIR group in comparison to the IR group. In the PIR group, Thiobarbituric acid reactive substance (TBARS) level had statistically significant decrease compared with IR group. Glutathione peroxidase (GSH-PX) levels were also significantly increased in the PIR group compared with I, IR and control groups. In the PI and PIR groups, catalase (CAT) levels were also significantly increased compared with I and IR groups (p=0.03 and p=0.07, respectively). Conclusion: Pregabalin may protect the damage of oxidative stress after ischemia + reperfusion. This result would illuminate clinical studies in the future. PMID:27403394

  14. Retino-choroidal ischemia in central retinal vein occlusion

    PubMed Central

    Hussain, Nazimul; Hussain, Anjli

    2014-01-01

    A 41-year-old gentleman with insulin dependent diabetes had decreased vision in the right eye due to non-ischemic central retinal vein occlusion with macular edema. One month following intravitreal ranibizumab, he developed retino-choroidal ischemia with further loss of vision. Authors show the fluorescein angiographic transition from non-ischemic central retinal vein occlusion to retino-choroidal ischemia. PMID:25473353

  15. Association between Anger and Mental Stress-Induced Myocardial Ischemia

    PubMed Central

    Pimple, Pratik; Shah, Amit; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon; Ibeanu, Ijeoma; Murrah, Nancy; Shallenberger, Lucy; Kelley, Mary; Raggi, Paolo; Vaccarino, Viola

    2014-01-01

    Background Mental stress-induced myocardial ischemia is associated with adverse prognosis in coronary artery disease patients. Anger is thought to be a trigger of acute coronary syndromes and is associated with increased cardiovascular risk; however, little direct evidence exists for a link between anger and myocardial ischemia. Methods [99mTc]sestamibi single-photon emission tomography was performed at rest, after mental stress (a social stressor with a speech task), and after exercise/pharmacological stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed difference score, the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. The Spielberger's State-Trait Anger Expression Inventory was used to assess different anger dimensions. Results The mean age was 50 years, 50% were female and 60% were non-white. After adjusting for demographic factors, smoking, coronary artery disease severity, depressive and anxiety symptoms, each interquartile range increment in state-anger score was associated with 0.36 units adjusted increase in ischemia as measured by the summed difference score (95% CI: 0.14-0.59); the corresponding association for trait-anger was 0.95 (95% CI: 0.21-1.69). Anger expression scales were not associated ischemia. None of the anger dimensions were related to ischemia during exercise/pharmacological stress. Conclusion Anger, both as an emotional state and as a personality trait, is significantly associated with propensity to develop myocardial ischemia during mental stress, but not during exercise/pharmacological stress. Patients with this psychological profile may be at increased risk for silent ischemia induced by emotional stress and this may translate into worse prognosis. PMID:25497256

  16. EEG Monitoring in Cerebral Ischemia: Basic Concepts and Clinical Applications.

    PubMed

    van Putten, Michel J A M; Hofmeijer, Jeannette

    2016-06-01

    EEG is very sensitive to changes in neuronal function resulting from ischemia. The authors briefly review essentials of EEG generation and the effects of ischemia on the underlying neuronal processes. They discuss the differential sensitivity of various neuronal processes to energy limitations, including synaptic disturbances. The clinical applications reviewed include continuous EEG monitoring during carotid surgery and acute ischemic stroke, and EEG monitoring for prognostication after cardiac arrest. PMID:27258443

  17. Mouse Transient Global Ischemia Two-Vessel Occlusion Model

    PubMed Central

    Pontarelli, Fabrizio; Ofengeim, Dimitry; Zukin, R. Suzanne; Jonas, Elizabeth A.

    2016-01-01

    Transient global ischemia in rodents induces delayed death of hippocampal CA1 neurons, as well as in some hilar neurons of the dentate gyrus, medium aspiny neurons of the striatum, pyramidal neurons in neocortical layers II, V and VI, and Purkinje neurons of the cerebellum. In contrast to focal ischemia that mimics regional stroke in humans, this model of global ischemia mimics the brain injury that occurs after human cardiac arrest. Early events include caspase activation, cleavage of anti-death Bcl-2 family proteins and large mitochondrial channel activity. Genetically engineered mice provide opportunities for study such as the knock-in mouse expressing a caspase-resistant form of Bcl-xL found to exhibit markedly reduced mitochondrial channel activity and reduced vulnerability to ischemia-induced neuronal death1. It is therefore relevant to adapt and develop a simple protocol for producing transient global ischemia in mouse2. The two-vessel occlusion model has been specifically developed to provide optimal outcomes in mouse and offers several advantages over the four-vessel occlusion model traditionally used in rat including the relative ease of the procedure as well as only a single day of surgery. However it should be noted that this procedure has a higher morbidity rate compared to other ischemia models as well as a higher degree of variability. These two disadvantages necessitate the use of a larger cohort of animals, which for many healthy breeding transgenic animals is a non-deterring factor.

  18. Neuroprotective effects of rutaecarpine on cerebral ischemia reperfusion injury

    PubMed Central

    Yan, Chunlin; Zhang, Ji; Wang, Shu; Xue, Guiping; Hou, Yong

    2013-01-01

    Rutaecarpine, an active component of the traditional Chinese medicine Tetradium ruticarpum, has been shown to improve myocardial ischemia reperfusion injury. Because both cardiovascular and cerebrovascular diseases are forms of ischemic vascular disease, they are closely related. We hypothesized that rutaecarpine also has neuroprotective effects on cerebral ischemia reperfusion injury. A cerebral ischemia reperfusion model was established after 84, 252 and 504 μg/kg carpine were given to mice via intraperitoneal injection, daily for 7 days. Results of the step through test, 2,3,5-triphenyl tetrazolium chloride dyeing and oxidative stress indicators showed that rutaecarpine could improve learning and memory ability, neurological symptoms and reduce infarction volume and cerebral water content in mice with cerebral ischemia reperfusion injury. Rutaecarpine could significantly decrease the malondialdehyde content and increase the activities of superoxide dismutase and glutathione peroxidase in mouse brain. Therefore, rutaecarpine could improve neurological function following injury induced by cerebral ischemia reperfusion, and the mechanism of this improvement may be associated with oxidative stress. These results verify that rutaecarpine has neuroprotective effects on cerebral ischemia reperfusion in mice. PMID:25206511

  19. Vinpocetine modulates metabolic activity and function during retinal ischemia.

    PubMed

    Nivison-Smith, Lisa; O'Brien, Brendan J; Truong, Mai; Guo, Cindy X; Kalloniatis, Michael; Acosta, Monica L

    2015-05-01

    Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues. PMID:25696811

  20. Methods for Acute and Subacute Murine Hindlimb Ischemia.

    PubMed

    Padgett, Michael E; McCord, Timothy J; McClung, Joseph M; Kontos, Christopher D

    2016-01-01

    Peripheral artery disease (PAD) is a leading cause of cardiovascular morbidity and mortality in developed countries, and animal models that reliably reproduce the human disease are necessary to develop new therapies for this disease. The mouse hindlimb ischemia model has been widely used for this purpose, but the standard practice of inducing acute limb ischemia by ligation of the femoral artery can result in substantial tissue necrosis, compromising investigators' ability to study the vascular and skeletal muscle tissue responses to ischemia. An alternative approach to femoral artery ligation is the induction of gradual femoral artery occlusion through the use of ameroid constrictors. When placed around the femoral artery in the same or different locations as the sites of femoral artery ligation, these devices occlude the artery over 1 - 3 days, resulting in more gradual, subacute ischemia. This results in less substantial skeletal muscle tissue necrosis, which may more closely mimic the responses seen in human PAD. Because genetic background influences outcomes in both the acute and subacute ischemia models, consideration of the mouse strain being studied is important in choosing the best model. This paper describes the proper procedure and anatomical placement of ligatures or ameroid constrictors on the mouse femoral artery to induce subacute or acute hindlimb ischemia in the mouse. PMID:27403963

  1. Methods for Acute and Subacute Murine Hindlimb Ischemia

    PubMed Central

    Padgett, Michael E.; McCord, Timothy J.; McClung, Joseph M.; Kontos, Christopher D.

    2016-01-01

    Peripheral artery disease (PAD) is a leading cause of cardiovascular morbidity and mortality in developed countries, and animal models that reliably reproduce the human disease are necessary to develop new therapies for this disease. The mouse hindlimb ischemia model has been widely used for this purpose, but the standard practice of inducing acute limb ischemia by ligation of the femoral artery can result in substantial tissue necrosis, compromising investigators' ability to study the vascular and skeletal muscle tissue responses to ischemia. An alternative approach to femoral artery ligation is the induction of gradual femoral artery occlusion through the use of ameroid constrictors. When placed around the femoral artery in the same or different locations as the sites of femoral artery ligation, these devices occlude the artery over 1-3 days, resulting in more gradual, subacute ischemia. This results in less substantial skeletal muscle tissue necrosis, which may more closely mimic the responses seen in human PAD. Because genetic background influences outcomes in both the acute and subacute ischemia models, consideration of the mouse strain being studied is important in choosing the best model. This paper describes the proper procedure and anatomical placement of ligatures or ameroid constrictors on the mouse femoral artery to induce subacute or acute hindlimb ischemia in the mouse. PMID:27403963

  2. Improved renal ischemia tolerance in females influences kidney transplantation outcomes

    PubMed Central

    Aufhauser, David D.; Wang, Zhonglin; Murken, Douglas R.; Bhatti, Tricia R.; Wang, Yanfeng; Ge, Guanghui; Redfield, Robert R.; Abt, Peter L.; Wang, Liqing; Reese, Peter P.; Hancock, Wayne W.; Levine, Matthew H.

    2016-01-01

    Experimentally, females show an improved ability to recover from ischemia-reperfusion injury (IRI) compared with males; however, this sex-dependent response is less established in humans. Here, we developed a series of murine renal ischemia and transplant models to investigate sex-specific effects on recovery after IRI. We found that IRI tolerance is profoundly increased in female mice compared with that observed in male mice and discovered an intermediate phenotype after neutering of either sex. Transplantation of adult kidneys from either sex into a recipient of the opposite sex followed by ischemia at a remote time resulted in ischemia recovery that reflected the sex of the recipient, not the donor, revealing that the host sex determines recovery. Likewise, renal IRI was exacerbated in female estrogen receptor α–KO mice, while female mice receiving supplemental estrogen before ischemia were protected. We examined data from the United Network for Organ Sharing (UNOS) to determine whether there is an association between sex and delayed graft function (DGF) in patients who received deceased donor renal transplants. A multivariable logistic regression analysis determined that there was a greater association with DGF in male recipients than in female recipients. Together, our results demonstrate that sex affects renal IRI tolerance in mice and humans and indicate that estrogen administration has potential as a therapeutic intervention to clinically improve ischemia tolerance. PMID:27088798

  3. A Program for Solving the Brain Ischemia Problem

    PubMed Central

    DeGracia, Donald J.

    2013-01-01

    Our recently described nonlinear dynamical model of cell injury is here applied to the problems of brain ischemia and neuroprotection. We discuss measurement of global brain ischemia injury dynamics by time course analysis. Solutions to proposed experiments are simulated using hypothetical values for the model parameters. The solutions solve the global brain ischemia problem in terms of “master bifurcation diagrams” that show all possible outcomes for arbitrary durations of all lethal cerebral blood flow (CBF) decrements. The global ischemia master bifurcation diagrams: (1) can map to a single focal ischemia insult, and (2) reveal all CBF decrements susceptible to neuroprotection. We simulate measuring a neuroprotectant by time course analysis, which revealed emergent nonlinear effects that set dynamical limits on neuroprotection. Using over-simplified stroke geometry, we calculate a theoretical maximum protection of approximately 50% recovery. We also calculate what is likely to be obtained in practice and obtain 38% recovery; a number close to that often reported in the literature. The hypothetical examples studied here illustrate the use of the nonlinear cell injury model as a fresh avenue of approach that has the potential, not only to solve the brain ischemia problem, but also to advance the technology of neuroprotection. PMID:24961411

  4. [Prognosis of acute ischemia of the lower limbs in patients over 80 years of age. A prospective study].

    PubMed

    Batt, M; Daune, B; Puch, J; Hassen-Khodja, R; Avril, G; Declemy, S; Le Bas, P

    1990-12-01

    To demonstrate the importance of age in the prognosis of acute lower limb ischemia, a prospective study was performed in 137 patients over 24 months. Group I contained 75 patients aged under 80 years and group II 62 patients aged over 80 years. Risk factors and previous history were equally distributed in the two groups. The level of arterial blockage and the treatment were comparable in the two groups. Mortality was higher in group II than in group I (p less than 0.01). In both groups deaths were principally due to cardiac causes and a revascularisation syndrome. Amputation at thigh level was more common in group II (p less than 0.01). Mortality was higher in group II for combined thigh level amputation and cardiac or coronary insufficiency (p less than 0.05). This study demonstrated that, in terms of prognosis of acute lower limb ischemia, the critical threshold is 80 years. PMID:2099941

  5. Thinking Critically about Critical Thinking

    ERIC Educational Resources Information Center

    Mulnix, Jennifer Wilson

    2012-01-01

    As a philosophy professor, one of my central goals is to teach students to think critically. However, one difficulty with determining whether critical thinking can be taught, or even measured, is that there is widespread disagreement over what critical thinking actually is. Here, I reflect on several conceptions of critical thinking, subjecting…

  6. Chapter 7. Mouse models of ischemic angiogenesis and ischemia-reperfusion injury.

    PubMed

    Greenberg, Joshua I; Suliman, Ahmed; Barillas, Samuel; Angle, Niren

    2008-01-01

    Ischemia and ischemia-reperfusion (I/R) events are distinct but interrelated processes etiologic to the most prevalent human diseases. A delicate balance exists whereby ischemic injury can result in beneficial angiogenesis or in detrimental reperfusion injury overwhelming the organism. Here, we describe in vivo models of ischemia and ischemia-reperfusion injury with emphasis on murine hindlimb ischemia models. We also provide a brief introduction to murine myocardial ischemia experiments. Each model is described in the context of human disease. Emphasis is made on the strengths and weaknesses of the available techniques, particularly as it relates to data analysis, interpretation, and translational relevance. PMID:19007664

  7. Effects of carbon monoxide on myocardial ischemia.

    PubMed Central

    Allred, E N; Bleecker, E R; Chaitman, B R; Dahms, T E; Gottlieb, S O; Hackney, J D; Pagano, M; Selvester, R H; Walden, S M; Warren, J

    1991-01-01

    The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. The exposures resulted in postexercise carboxyhemoglobin (COHb) levels of 0.6% +/- 0.3%, 2.0% +/- 0.1%, and 3.9% +/- 0.1%. The results obtained on the 2%-COHb day and 3.9%-COHb day were compared to those on the room air day. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) decreases in the time to development of ischemic ST-segment changes after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. In addition, there were 4.2% (p = 0.027) and 7.1% (p = 0.002) decreases in time to the onset of angina after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre- versus postexposure exercise tests at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease. PMID:2040254

  8. Critical Care

    MedlinePlus

    Critical care helps people with life-threatening injuries and illnesses. It might treat problems such as complications from surgery, ... attention by a team of specially-trained health care providers. Critical care usually takes place in an ...

  9. Biphasic modulation of the mitochondrial electron transport chain in myocardial ischemia and reperfusion

    PubMed Central

    Lee, Hsin-Ling; Chen, Chwen-Lih; Yeh, Steve T.; Zweier, Jay L.

    2012-01-01

    Mitochondrial electron transport chain (ETC) is the major source of reactive oxygen species during myocardial ischemia-reperfusion (I/R) injury. Ischemic defect and reperfusion-induced injury to ETC are critical in the disease pathogenesis of postischemic heart. The properties of ETC were investigated in an isolated heart model of global I/R. Rat hearts were subjected to ischemia for 30 min followed by reperfusion for 1 h. Studies of mitochondrial function indicated a biphasic modulation of electron transfer activity (ETA) and ETC protein expression during I/R. Analysis of ETAs in the isolated mitochondria indicated that complexes I, II, III, and IV activities were diminished after 30 min of ischemia but increased upon restoration of flow. Immunoblotting analysis and ultrastructural analysis with transmission electron microscopy further revealed marked downregulation of ETC in the ischemic heart and then upregulation of ETC upon reperfusion. No significant difference in the mRNA expression level of ETC was detected between ischemic and postischemic hearts. However, reperfusion-induced ETC biosynthesis in myocardium can be inhibited by cycloheximide, indicating the involvement of translational control. Immunoblotting analysis of tissue homogenates revealed a similar profile in peroxisome proliferator-activated receptor-γ coactivator-1α expression, suggesting its essential role as an upstream regulator in controlling ETC biosynthesis during I/R. Significant impairment caused by ischemic and postischemic injury was observed in the complexes I- III. Analysis of NADH ferricyanide reductase activity indicated that injury of flavoprotein subcomplex accounts for 50% decline of intact complex I activity from ischemic heart. Taken together, our findings provide a new insight into the molecular mechanism of I/R-induced mitochondrial dysfunction. PMID:22268109

  10. Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat.

    PubMed

    Regal, Jean F; Lillegard, Kathryn E; Bauer, Ashley J; Elmquist, Barbara J; Loeks-Johnson, Alex C; Gilbert, Jeffrey S

    2015-01-01

    Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise. Using the reduced uteroplacental perfusion pressure (RUPP) model of placental ischemia-induced hypertension in the rat, we determined the effect of neutrophil depletion on blood pressure and fetal resorptions. Neutrophils were depleted with repeated injections of polyclonal rabbit anti-rat polymorphonuclear leukocyte (PMN) antibody (antiPMN). Rats received either antiPMN or normal rabbit serum (Control) on 13.5, 15.5, 17.5, and 18.5 days post conception (dpc). On 14.5 dpc, rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP). On 18.5 dpc, carotid arterial catheters were placed and mean arterial pressure (MAP) was measured on 19.5 dpc. Neutrophil-depleted rats had reduced circulating neutrophils from 14.5 to 19.5 dpc compared to Control, as well as decreased neutrophils in lung and placenta on 19.5 dpc. MAP increased in RUPP Control vs Sham Control rats, and neutrophil depletion attenuated this increase in MAP in RUPP rats without any effect on Sham rats. The RUPP-induced increase in fetal resorptions and complement activation product C3a were not affected by neutrophil depletion. Thus, these data are the first to indicate that neutrophils play an important role in RUPP hypertension and that cells of the innate immune system may significantly contribute to pregnancy-induced hypertension. PMID:26135305

  11. Endogenous Protease Nexin-1 Protects against Cerebral Ischemia

    PubMed Central

    Mirante, Osvaldo; Price, Melanie; Puentes, Wilfredo; Castillo, Ximena; Benakis, Corinne; Thevenet, Jonathan; Monard, Denis; Hirt, Lorenz

    2013-01-01

    The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin’s endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1−/− mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection. PMID:23949634

  12. Endogenous protease nexin-1 protects against cerebral ischemia.

    PubMed

    Mirante, Osvaldo; Price, Melanie; Puentes, Wilfredo; Castillo, Ximena; Benakis, Corinne; Thevenet, Jonathan; Monard, Denis; Hirt, Lorenz

    2013-01-01

    The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin's endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1(-/-) mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection. PMID:23949634

  13. Intravascular heparin protects muscle flaps from ischemia/reperfusion injury.

    PubMed

    Li, X; Cooley, B C; Fowler, J D; Gould, J S

    1995-01-01

    Heparin has been found to decrease ischemia/reperfusion injury in skeletal muscle and other tissue/organ systems. The timing of heparin administration to the muscle vasculature has not been explored. We investigated the use of heparinized blood as a washout solution during ischemia to reduce ischemia/reperfusion injury. A rat cutaneous maximus muscle free flap was subjected to a 10-hr period of room temperature ischemia, then was heterotopically transplanted to the groin via microsurgical revascularization to the femoral vessels. In three experimental groups, flaps were subjected to brief ex vivo perfusion with autologous heparinized blood, at 2, 5, or 8 hr into the 10-hr ischemic interval. In the two other groups, the flaps were not perfused, and the animals were systemically heparinized either before ischemia or before transplantation, respectively. A control group underwent no flap perfusion or systemic heparinization. After transplantation, flaps were given a 48-hr period of in vivo reperfusion, then were harvested for evaluation. Flaps undergoing ex vivo perfusion or preischemic heparinization had no significant differences in weight gain (edema) compared with flaps receiving posttransplant heparinization or no heparinization (controls). The dehydrogenase staining of muscle biopsies was significantly faster (indicative of viable tissue) for perfused flaps and the flaps for which the animals received preischemic heparinization, when compared with flaps for which the animals received posttransplant heparinization or no heparinization. From these results, we conclude that heparin offers protection from ischemia/reperfusion injury when it can be introduced into the vascular network either prior to or during the ischemia period. These findings suggest the possibility of using heparinized washout solutions to enhance survival in amputated extremities. PMID:7783611

  14. Spin label oximetry to assess extracellular oxygen during myocardial ischemia.

    PubMed

    Baker, J E; Froncisz, W; Joseph, J; Kalyanaraman, B

    1997-01-01

    We describe real-time measurement of myocardial oxygen consumption during ischemia in the intact heart. Measurement of extracellular oxygen concentration during myocardial ischemia by spin label oximetry has been limited by ischemia-induced reduction of the neutral, water-soluble nitroxide TEMPONE. We have overcome this problem by encapsulating the nitroxides. Isolated immature (7-10 d old) rabbit hearts (n = 8) were perfused aerobically within the cavity of a loop gap resonator with bicarbonate buffer containing an oxygen-sensitive, lipid-soluble nitroxide (14N-TEMPO laurate in FC-43 perfluorocarbon micelles) and a much less oxygen-sensitive and positively charged nitroxide (15N-TEMPO choline in multilamellar vesicles) as an internal standard. The ratio of the ESR signal amplitudes of these nitroxides was used as a sensitive index of oxygen concentration. Sequestration of the nitroxides decreased their reduction rate by ascorbate in comparison with nonsequestered nitroxides. Hearts were subjected to 60 min of global no-flow ischemia at 20 degrees C. Extracellular oxygen content (mean +/- SD) during aerobic perfusion was 1195 +/- 55 mumol/liter. The electron spin resonance signal from TEMPO laurate increased with the onset and progression of ischemia, consistent with a decrease in extracellular oxygen, while the signal for TEMPO choline was relatively unchanged. Extracellular oxygen content after 40 and 60 min of ischemia was reduced to 393 +/- 27 mumol/liter (p < .05) and 61 +/- 5 mumol/liter (p < .05), respectively. We conclude that spin-label oximetry can directly and precisely measure myocardial oxygen consumption at constant temperature during ischemia in the intact heart. PMID:8958135

  15. TGF-β1 prevents simulated ischemia/reperfusion-induced cardiac fibroblast apoptosis by activation of both canonical and non-canonical signaling pathways.

    PubMed

    Vivar, Raúl; Humeres, Claudio; Ayala, Pedro; Olmedo, Ivonne; Catalán, Mabel; García, Lorena; Lavandero, Sergio; Díaz-Araya, Guillermo

    2013-06-01

    Ischemia/reperfusion injury is a major cause of myocardial death. In the heart, cardiac fibroblasts play a critical role in healing post myocardial infarction. TGF-β1 has shown cardioprotective effects in cardiac damage; however, if TGF-β1 can prevent cardiac fibroblast death triggered by ischemia/reperfusion is unknown. Therefore, we test this hypothesis, and whether the canonical and/or non-canonical TGF-β1 signaling pathways are involved in this protective effect. Cultured rat cardiac fibroblasts were subjected to simulated ischemia/reperfusion. Cell viability was analyzed by trypan blue exclusion and propidium iodide by flow cytometry. The processing of procaspases 8, 9 and 3 to their active forms was assessed by Western blot, whereas subG1 population was evaluated by flow cytometry. Levels of total and phosphorylated forms of ERK1/2, Akt and Smad2/3 were determined by Western blot. The role of these signaling pathways on the protective effect of TGF-β1 was studied using specific chemical inhibitors. Simulated ischemia over 8h triggers a significant cardiac fibroblast death, which increased by reperfusion, with apoptosis actively involved. These effects were only prevented by the addition of TGF-β1 during reperfusion. TGF-β1 pretreatment increased the levels of phosphorylated forms of ERK1/2, Akt and Smad2/3. The inhibition of ERK1/2, Akt and Smad3 also blocked the preventive effects of TGF-β1 on cardiac fibroblast apoptosis induced by simulated ischemia/reperfusion. Overall, our data suggest that TGF-β1 prevents cardiac fibroblast apoptosis induced by simulated ischemia-reperfusion through the canonical (Smad3) and non canonical (ERK1/2 and Akt) signaling pathways. PMID:23416528

  16. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage

    NASA Astrophysics Data System (ADS)

    Webb, Andrew; Bond, Richard; McLean, Peter; Uppal, Rakesh; Benjamin, Nigel; Ahluwalia, Amrita

    2004-09-01

    Nitric oxide (NO) is thought to protect against the damaging effects of myocardial ischemia-reperfusion injury, whereas xanthine oxidoreductase (XOR) normally causes damage through the generation of reactive oxygen species. In the heart, inorganic nitrite has the potential to act as an endogenous store of NO, liberated specifically during ischemia. Using a detection method that we developed, we report that under ischemic conditions both rat and human homogenized myocardium and the isolated perfused rat heart (Langendorff preparation) generate NO from in a reaction that depends on XOR activity. Functional studies of rat hearts in the Langendorff apparatus showed that nitrite (10 and 100 µM) reduced infarct size from 47.3 ± 2.8% (mean percent of control ± SEM) to 17.9 ± 4.2% and 17.4 ± 1.0%, respectively (P < 0.001), and was associated with comparable improvements in recovery of left ventricular function. This protective effect was completely blocked by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO). In summary, the generation of NO from •, rather than damaging.

  17. Critical Thoughts on Critical Thinking

    ERIC Educational Resources Information Center

    Cody, Dean E.

    2006-01-01

    Scholars in many academic areas, including librarians, devote a significant amount of thought to critical thinking. Surveying views of its use and possibility, the author considers some key librarians' thoughts on critical thinking. In conclusion, the inability to define critical thinking means that librarians need to emphasize control of…

  18. Critical Thinking vs. Critical Consciousness

    ERIC Educational Resources Information Center

    Doughty, Howard A.

    2006-01-01

    This article explores four kinds of critical thinking. The first is found in Socratic dialogues, which employ critical thinking mainly to reveal logical fallacies in common opinions, thus cleansing superior minds of error and leaving philosophers free to contemplate universal verities. The second is critical interpretation (hermeneutics) which…

  19. Critically Thinking about Critical Thinking

    ERIC Educational Resources Information Center

    Weissberg, Robert

    2013-01-01

    In this article, the author states that "critical thinking" has mesmerized academics across the political spectrum and that even high school students are now being called upon to "think critically." He furthers adds that it is no exaggeration to say that "critical thinking" has quickly evolved into a scholarly…

  20. How Critical Is Critical Thinking?

    ERIC Educational Resources Information Center

    Shaw, Ryan D.

    2014-01-01

    Recent educational discourse is full of references to the value of critical thinking as a 21st-century skill. In music education, critical thinking has been discussed in relation to problem solving and music listening, and some researchers suggest that training in critical thinking can improve students' responses to music. But what exactly is…

  1. Normobaric Oxygen Therapy for Scleral Ischemia or Melt

    PubMed Central

    Sharifipour, Farideh; Panahi-Bazaz, Mahmoodreza; Idani, Esmaeil; Malekahmadi, Mohammad; Feizi, Sepehr

    2012-01-01

    Purpose To investigate the efficacy of normobaric oxygen (NBO) therapy for treatment of scleral ischemia or melt. Methods This prospective interventional case series includes 9 eyes of 8 patients with scleral ischemia or melt of diverse etiologies. Following the failure of conventional medical and/or surgical therapy to improve ischemia or upon clinical deterioration, NBO was initiated. All patients received 100% NBO at flow rate of 10 liters/minute by face mask for 1 hour, twice daily until complete vascularization of ischemic areas. Main outcome measures were improvement of scleral ischemia and healing of conjunctival epithelial defects. Results NBO therapy led to epithelialization and vascularization of the ischemic sclera in all eyes; the repair process began 3-4 days after NBO had been initiated and was completed in 18.1±4.7 (range, 10-25) days. All patients remained stable over a 9-month follow-up period. Conclusion NBO therapy seems effective for treatment of scleral ischemia or melt, and hence can be considered as a non-invasive alternative to surgical intervention in these conditions. PMID:23504548

  2. Optical Monitoring and Detection of Spinal Cord Ischemia

    PubMed Central

    Mesquita, Rickson C.; D’Souza, Angela; Bilfinger, Thomas V.; Galler, Robert M.; Emanuel, Asher; Schenkel, Steven S.; Yodh, Arjun G.; Floyd, Thomas F.

    2013-01-01

    Spinal cord ischemia can lead to paralysis or paraparesis, but if detected early it may be amenable to treatment. Current methods use evoked potentials for detection of spinal cord ischemia, a decades old technology whose warning signs are indirect and significantly delayed from the onset of ischemia. Here we introduce and demonstrate a prototype fiber optic device that directly measures spinal cord blood flow and oxygenation. This technical advance in neurological monitoring promises a new standard of care for detection of spinal cord ischemia and the opportunity for early intervention. We demonstrate the probe in an adult Dorset sheep model. Both open and percutaneous approaches were evaluated during pharmacologic, physiological, and mechanical interventions designed to induce variations in spinal cord blood flow and oxygenation. The induced variations were rapidly and reproducibly detected, demonstrating direct measurement of spinal cord ischemia in real-time. In the future, this form of hemodynamic spinal cord diagnosis could significantly improve monitoring and management in a broad range of patients, including those undergoing thoracic and abdominal aortic revascularization, spine stabilization procedures for scoliosis and trauma, spinal cord tumor resection, and those requiring management of spinal cord injury in intensive care settings. PMID:24358279

  3. Fluorometry of ischemia reperfusion injury in rat lungs in vivo

    NASA Astrophysics Data System (ADS)

    Sepehr, R.; Staniszewski, K.; Jacobs, E. R.; Audi, S.; Ranji, Mahsa

    2013-02-01

    Previously we demonstrated the utility of optical fluorometry to evaluate lung tissue mitochondrial redox state in isolated perfused rats lungs under various chemically-induced respiratory states. The objective of this study was to evaluate the effect of acute ischemia on lung tissue mitochondrial redox state in vivo using optical fluorometry. Under ischemic conditions, insufficient oxygen supply to the mitochondrial chain should reduce the mitochondrial redox state calculated from the ratio of the auto-fluorescent mitochondrial metabolic coenzymes NADH (Nicotinamide Adenine Dinucleotide) and FAD (Flavoprotein Adenine Dinucleotide). The chest of anesthetized, and mechanically ventilated Sprague-Dawley rat was opened to induce acute ischemia by clamping the left hilum to block both blood flow and ventilation to one lung for approximately 10 minutes. NADH and FAD fluorescent signals were recorded continuously in a dark room via a fluorometer probe placed on the pleural surface of the left lung. Acute ischemia caused a decrease in FAD and an increase in NADH, which resulted in an increase in the mitochondrial redox ratio (RR=NADH/FAD). Restoration of blood flow and ventilation by unclamping the left hilum returned the RR back to its baseline. These results (increase in RR under ischemia) show promise for the fluorometer to be used in a clinical setting for evaluating the effect of pulmonary ischemia-reperfusion on lung tissue mitochondrial redox state in real time.

  4. Effect of curcumin on diabetic rat model of cerebral ischemia.

    PubMed

    Miao, Mingsan; Cheng, Bolin; Li, Min

    2015-01-01

    To investigate the effect of curcumin on cerebral ischemia in diabetic rats the effects and features. intravenous injection alloxan diabetes model, to give alloxan first seven days the tail measured blood glucose value, the election successful model rats were fed with large, medium and small doses of curcumin suspension, Shenqijiangtang suspension and the same volume of saline, administered once daily. The first 10 days after administration 2h (fasting 12h) rat tail vein blood glucose values measured in the first 20 days after administration of 2h (fasting 12h), do cerebral ischemia surgery; rapid carotid artery blood after 30min rats were decapitated, blood serum, blood glucose and glycated serum protein levels; take part of the brain homogenates plus nine times the amount of normal saline, made 10 percent of brain homogenates. Another part of the brain tissue, in the light microscope observation of pathological tissue. Compared with model group, large, medium and small doses of curcumin can significantly lower blood sugar and glycated serum protein levels, significantly reduced brain homogenates lactic acid content and lactate dehydrogenase activity; large, medium-dose curcumin can significantly increase brain homogenates Na(+)-K(+)-ATP activity, dose curcumin can significantly improve brain homogenates Ca(+)-Mg(+)- ATP activity. Curcumin can reduce blood sugar in diabetic rat model of cerebral ischemia and improve brain energy metabolism, improve their brain tissue resistance to ischemia and hypoxia, cerebral ischemia in diabetic rats have a good drop the role of sugar and protect brain tissue. PMID:25631517

  5. Assessment of Myocardial Ischemia with Cardiovascular Magnetic Resonance

    PubMed Central

    Heydari, Bobak; Jerosch-Herold, Michael; Kwong, Raymond Y.

    2014-01-01

    Assessment of myocardial ischemia in symptomatic patients remains a common and challenging clinical situation faced by physicians. Risk stratification by presence of ischemia provides important utility for both prognostic assessment and management. Unfortunately, current noninvasive modalities possess numerous limitations and have limited prognostic capacity. More recently, ischemia assessment by cardiovascular magnetic resonance (CMR) has been shown to be a safe, available, and potentially cost-effective alternative with both high diagnostic and prognostic accuracy. Cardiovascular magnetic resonance has numerous advantages over other noninvasive methods, including high temporal and spatial resolution, relatively few contraindications, and absence of ionizing radiation. Furthermore, studies assessing the clinical utility and cost effectiveness of CMR in the short-term setting for patients without evidence of an acute myocardial infarction have also demonstrated favorable results. This review will cover techniques of ischemia assessment with CMR by both stress-induced wall motion abnormalities as well as myocardial perfusion imaging. The diagnostic and prognostic performance studies will also be reviewed, and the use of CMR for ischemia assessment will be compared with other commonly used noninvasive modalities. PMID:22014487

  6. The protein kinase 2 inhibitor tetrabromobenzotriazole protects against renal ischemia reperfusion injury

    PubMed Central

    Ka, Sun-O; Hwang, Hong Pil; Jang, Jong-Hwa; Hyuk Bang, In; Bae, Ui-Jin; Yu, Hee Chul; Cho, Baik Hwan; Park, Byung-Hyun

    2015-01-01

    Protein kinase 2 (CK2) activation was reported to enhance reactive oxygen species production and activate the nuclear factor κB (NF-κB) pathway. Because oxidative stress and inflammation are critical events for tissue destruction during ischemia reperfusion (I/R), we sought to determine whether CK2 was important in the renal response to I/R. Mice underwent 25 min of renal ischemia and were then reperfused. We confirmed an increased expression of CK2α during the reperfusion period, while expression of CK2β remained consistent. We administered tetrabromobenzotriazole (TBBt), a selective CK2α inhibitor before inducing I/R injury. Mice subjected to I/R injury showed typical patterns of acute kidney injury; blood urea nitrogen and serum creatinine levels, tubular necrosis and apoptosis, inflammatory cell infiltration and proinflammatory cytokine production, and oxidative stress were markedly increased when compared to sham mice. However, pretreatment with TBBt abolished these changes and improved renal function and architecture. Similar renoprotective effects of CK2α inhibition were observed for emodin. Renoprotective effects of CK2α inhibition were associated with suppression of NF-κB and mitogen activated protein kinase (MAPK) pathways. Taken together, these results suggest that CK2α mediates proapoptotic and proinflammatory signaling, thus the CK2α inhibitor may be used to prevent renal I/R injuries observed in clinical settings. PMID:26423352

  7. Targeting Complement Pathways During Cold Ischemia and Reperfusion Prevents Delayed Graft Function.

    PubMed

    Yu, Z X; Qi, S; Lasaro, M A; Bouchard, K; Dow, C; Moore, K; Wu, Z; Barama, A; Xu, J; Johnson, K; Marozsan, A J; Wang, Y

    2016-09-01

    The complement system plays a critical role in ischemia-reperfusion injury (IRI)-mediated delayed graft function (DGF). To better understand the roles of complement activation pathways in IRI in kidney transplantation, donor kidneys were treated ex vivo with terminal complement pathway (TP) inhibitor, anti-rat C5 mAb 18A10, or complement alternative pathway (AP) inhibitor TT30 for 28 h at 4°C pretransplantation in a syngeneic kidney transplantation rat model. All 18A10- and 67% of TT30-pretreated grafts, but only 16.7% of isotype control-pretreated grafts, survived beyond day 21 (p < 0.01). Inhibitor treatment in the final 45 min of 28-h cold ischemia (CI) similarly improved graft survival. Systemic posttransplant treatment with 18A10 resulted in 60% increased graft survival beyond day 21 (p < 0.01), while no TT30-treated rat survived > 6 days. Our results demonstrate that AP plays a prominent role during CI and that blocking either the AP or, more effectively the TP prevents ischemic injury and subsequent DGF. Multiple complement pathways may be activated and contribute to reperfusion injury; blocking the TP, but not the AP, posttransplant is effective in preventing reperfusion injury and increasing graft survival. These results demonstrate the feasibility of using complement inhibitors for prevention of DGF in humans. PMID:27003920

  8. Maternal serum ischemia modified albumin as a marker for hypertensive disorders of pregnancy: a pilot study

    PubMed Central

    Vyakaranam, Sapna; Bhongir, Aparna Varma; Patlolla, Dakshayani; Chintapally, Rekha

    2015-01-01

    Background Hypoxia driven oxidative stress of the placenta contributes to the pathogenesis of preeclampsia. Serum Ischemia Modified Albumin (IMA) has recently emerged as an oxidative stress marker, used in diagnosis of cardiac ischemia. Aim: To determine the efficiency of serum IMA in differentiating hypertensive disorders of pregnancy (pregnancy induced hypertension, preeclampsia) from normal pregnancy. Methods It was a case control study. Pregnant women ≥32 weeks of gestation. Study population were included 3 groups, 19 Normotensive Pregnant (NP) women as controls, 18 pregnant women with Pregnancy Induced Hypertension (PIH) and 19 with preeclampsia (PE). Serum IMA was estimated by Enzyme Linked Immune Sorbent Assay (ELISA). Results were analyzed by student ‘t’test. Critical values for serum IMA were obtained by Receiver Operation Characteristics (ROC) curves. Results Serum IMA levels were significantly elevated in PE (56.84 ± 21.57 ng/ml) when compared with PIH (36.24 ± 14.51 ng/ml) and NP (35.47 ± 11.58 ng/ml) (P value <0.001). With a cutoff of 38.33 ng/ml, sensitivity and specificity for preeclampsia was 88.9% and 73.7% respectively. Conclusions Our study demonstrated that serum IMA, an oxidative stress marker is elevated in PE & PIH. Hence serum IMA can undergo further evaluation as a marker of PE. PMID:26636109

  9. Brain tissue oxygen, carbon dioxide, and pH in neurosurgical patients at risk for ischemia.

    PubMed

    Hoffman, W E; Charbel, F T; Edelman, G

    1996-03-01

    A sensor that measures oxygen pressure (PO2), carbon dioxide pressure (PCO2), and pH was evaluated in brain tissue of patients at risk for ischemia. The sensor is 0.5 mm in diameter and was inserted into cortex tissue in 14 patients undergoing craniotomy for cerebrovascular surgery. A compromised cerebral circulation was identified in 8 of 14 patients by single photon emission computed tomography (SPECT) scan, cerebral angiography, and transient ischemic episodes before surgery. Under baseline conditions with isoflurane anesthesia and normal blood gases, tissue P02 was lower in the eight compromised compared to six noncompromised patients (noncompromised 37 +/- 12 mm Hg, compromised 10 +/- 5 mm Hg; P < 0.05), PCO2 was increased (noncompromised 49 +/- 5 mm Hg, compromised 72 +/- 23 mm Hg; P < 0.05), and pH was decreased (noncompromised 7.16 +/- 0.08, compromised 6.82 +/- 0.21; P < 0.05). Critical tissue values for the identification of ischemia were a P02 of 20 mm Hg, PCO2 of 60 mm Hg, and a pH of 7.0. These results suggest that brain tissue measures of P02, PCO2, and pH provide information on the adequacy of cerebral perfusion in neurosurgical patients. PMID:8623965

  10. Primary Infrainguinal Subintimal Angioplasty in Diabetic Patients

    SciTech Connect

    Bargellini, Irene Petruzzi, Pasquale; Scatena, Alessia; Cioni, Roberto; Cicorelli, Antonio; Vignali, Claudio; Rizzo, Loredana; Piaggesi, Alberto; Bartolozzi, Carlo

    2008-07-15

    The aim of this study was to prospectively evaluate technical and clinical results of infrainguinal subintimal angioplasty in a series of diabetic patients with limb-threatening ischemia. From July 2003 to December 2007, 60 consecutive diabetic patients (M/F = 41/19; mean age, 69.4 {+-} 9.4 years) with Fontaine stage IV critical limb ischemia, not suitable for surgical recanalization, underwent primary infrainguinal subintimal angioplasty. The technical success, perioperative morbidity and mortality, and clinical success (defined by ulcer healing) were evaluated. Kaplan-Meier life-table analysis was obtained for cumulative clinical success, limb salvage, and survival rates. The procedure was technically successful in 55 of 60 (91.7%) patients; in 5 cases we were not able to achieve a reentry. Periprocedural mortality was 5% (3 patients); three patients (5%) required major amputation periprocedurally. Mean follow-up was 23 months (range, 0-48 months). On an intention-to-treat basis, the limb salvage rate was 93.3% (56/60 patients); ulcer healing was observed in 45 of 60 (75%) patients and it was significantly (p < 0.05) associated with serum creatinine and HbA1c levels, diabetes duration, and infrapopliteal recanalization. One- and three-year cumulative survival rates were 91.5% and 83.1%, respectively; serum creatinine levels, patient age, and clinical success were significant predictors of survival. In conclusion, infrainguinal primary subintimal angioplasty is a safe and effective treatment in diabetic patients with limb-threatening ischemia not suitable for surgical recanalization. This procedure is aimed to create a 'temporary bypass' that facilitates ulcer healing.

  11. Evaluation and treatment of chronic digital ischemia.

    PubMed Central

    Wilgis, E F

    1981-01-01

    Forty-two patients were evaluated and treated during the past five years at the Union Memorial Hospital Hand Center with the diagnosis of chronic digital ischemia. These patients with this syndrome, manifested by pain, severe cold intolerance and occasional tip ulceration, all were failures of conventional conservative treatment of vasodilators, tobacco abstinence and beta blocking agents. The evaluation consisted of first ruling out large vessel disease by noninvasive techniques of angiography. The patients underwent a variety of noninvasive diagnostic tests including Doppler examination, pulse volume recordings with cold stress, radioisotope scanning of the digital circulation and peripheral sympathetic block of the digital nerves. Treatment included direct microvascular reconstruction of the distal ulnar or radial artery and palmar arch, in ten patients, thermal biofeedback, in 22 patients and a new surgical procedure-digital sympathectomy, in ten patients, involving 18 digits. Eight of ten patients with palmar arch reconstruction improved with seven of ten having patent vein grafts. Thermal biofeedback has been helpful in 20 patients. Testing shows that an increase in digital perfusion can be initiated by all patients. However, only 70% can achieve this improvement. Digital sympathectomy consists of isolating the terminal branches of the sympathetic nerves which travel with the peripheral nerves, dividing these branches and stripping the adventitia of the digital arteries. Eight of nine patients have the experienced improvement in digital circulation, as manifested by pulse volume recordings after operation and radioisotope studies. Pain is substantially alleviated and the ulcers healed. All of these patients responded before operation to the digital nerve block with measured increased in digital perfusion. PMID:7247519

  12. [Protective effect of lornoxicam on development of myocardial infarction in rats under conditions of ischemia and ischemia-reperfusion].

    PubMed

    Gavrilova, S A; Lipina, T V; Zagidullin, T R; Fominykh, E S; Golubeva, A V; Varenik, E N; Parnes, E Ia; Semenov, P A

    2008-01-01

    Activation of inflammation and enzyme cyclooxygenase with formation of proinflammatory prostaglandins is a key element of development of myocardial infarction in patients with acute coronary syndrome. Basing on literature data and own experience we suggested that single intravenous injection of 230 mg/kg of nonselective inhibitor of type 1 and 2 cyclooxygenase lornaxicam in the phase of initialization of inflammation 20 min after onset of ischemia would lead to reduction of myocardial infarction volume in rats in irreversible ischemia and ischemia with subsequent reperfusion. The conducted study allowed to reveal that administration of lornoxicam in recommended for human use dose lowered mortality of animals and increased number of capillaries per one cardiomyocyte in case of irreversible coronary artery occlusion. In ischemia-reperfusion as in irreversible myocardial ischemia lornoxicam reduced volume of necrosis and degree of thinning of left ventricular wall in the region of infarction, and lowered volume of connective tissue in periinfarction zone of the myocardium in remote period. PMID:19076093

  13. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

    PubMed Central

    Shamsaei, Nabi; Khaksari, Mehdi; Erfani, Sohaila; Rajabi, Hamid; Aboutaleb, Nahid

    2015-01-01

    Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral ischemic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks). Then rats underwent cerebral ischemia induction through occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic exercise significantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration. PMID:26487851

  14. Effect of brain microdialysis on aminergic transmitter levels in repeated cerebral global transient ischemia in rat.

    PubMed

    Thaminy, S; Bellissant, E; Maginn, M; Decombe, R; Allain, H; Bentué-Ferrer, D

    1996-12-28

    The effect of repeated transient global ischemia and microdialysis on changes in aminergic neurotransmitter release was investigated using the rat four-vessel occlusion model of global ischemia. To examine the possible transient or permanent changes in neurotransmitter release, ischemia was induced at varying time points in 5 groups of rats. The first ischemia occurred either 24 h (groups I, II, IV, V) or 96 h (group III) following vertebral artery electro-coagulation and guide probe implantation(s), and the second ischemia was induced either 48 h (groups I, IV, V) or 72 h (group II) following the first ischemia. To assess the consequence of repeated microdialysis on the results, one group of rats (group IV) was not dialysed during the first ischemia and another group (group V) was bilaterally dialysed during the second ischemia. Finally, amphetamine-induced neurotransmitter release was also studied in rats submitted to ischemia and compared with that in normal rats. In each case, dopamine, serotonin and their main metabolites were measured by HPLC with electrochemical detection. Monoamine release was inhibited during the second episode of transient ischemia; this non-release was linked to the repeated microdialysis and not to the repeated ischemia. Although the results of chronic studies using brain microdialysis have been widely recognized as valid, the findings presented here indicate that combined with ischemia, probe reinsertion modifies the level of neurotransmitter release. PMID:9007758

  15. Ischemia-induced mitochondrial apoptosis is significantly attenuated by ischemic preconditioning.

    PubMed

    Racay, Peter; Chomova, Maria; Tatarkova, Zuzana; Kaplan, Peter; Hatok, Jozef; Dobrota, Dusan

    2009-09-01

    Ischemic preconditioning (IPC) represents an important adaptation of CNS to sub-lethal ischemia, which results in increased tolerance of CNS to the lethal ischemia. Ischemia-induced mitochondrial apoptosis is considered to be an important event leading to neuronal cell death after cerebral blood flow arrest. In presented study, we have determined the effect of IPC on ischemia/reperfusion-induced mitochondrial apoptosis. Global brain ischemia was induced by permanent occlusion of vertebral arteries and temporal occlusion of carotid arteries for 15 min. Rats were preconditioned by 5 min of sub-lethal ischemia and 2 days later 15 min of lethal ischemia was induced. With respect to mitochondrial apoptosis initiation, translocation of p53 to mitochondria was observed in hippocampus but not in cerebral cortex. However, level of both apoptotic bax and anti-apoptotic bcl-xl in both hippocampal and cortical mitochondria was unchanged after global brain ischemia. Detection of genomic DNA fragmentation as well as Fluoro-Jade C staining showed that ischemia induces apoptosis in vulnerable CA1 layer of rat hippocampus. IPC abolished completely ischemia-induced translocation of p53 to mitochondria and had significant protective effect on ischemia-induced DNA fragmentation. In addition, significant decrease of Fluoro-Jade C positive cells was observed as well. Our results indicate that IPC abolished almost completely both initiation and execution of mitochondrial apoptosis induced by global brain ischemia. PMID:19283470

  16. Reformulated meat products protect against ischemia-induced cardiac damage.

    PubMed

    Asensio-Lopez, M C; Lax, A; Sanchez-Mas, J; Avellaneda, A; Planes, J; Pascual-Figal, D A

    2016-02-17

    The protective effects of the antioxidants present in food are of great relevance for cardiovascular health. This study evaluates whether the extracts from reformulated meat products with a reduction in fat and/or sodium content exert a cardioprotective effect against ischemia-induced oxidative stress in cardiomyocytes, compared with non-meat foods. Ischemic damage caused loss of cell viability, increased reactive oxygen species and lipid peroxidation and decreased the antioxidant activity. Pretreatment for 24 h with digested or non-digested extracts from reformulated meat products led to protection against ischemia-induced oxidative damage: increased cell viability, reduced oxidative stress and restored the antioxidant activity. Similar results were obtained using extracts from tuna fish, but not with the extracts of green peas, salad or white beans. These results suggest that reformulated meat products have a beneficial impact in protecting cardiac cells against ischemia, and they may represent a source of natural antioxidants with benefits for cardiovascular health. PMID:26751429

  17. Myocardial perfusion imaging for detection of silent myocardial ischemia

    SciTech Connect

    Beller, G.A.

    1988-04-21

    Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging. 11 references.

  18. Criticality Model

    SciTech Connect

    A. Alsaed

    2004-09-14

    The ''Disposal Criticality Analysis Methodology Topical Report'' (YMP 2003) presents the methodology for evaluating potential criticality situations in the monitored geologic repository. As stated in the referenced Topical Report, the detailed methodology for performing the disposal criticality analyses will be documented in model reports. Many of the models developed in support of the Topical Report differ from the definition of models as given in the Office of Civilian Radioactive Waste Management procedure AP-SIII.10Q, ''Models'', in that they are procedural, rather than mathematical. These model reports document the detailed methodology necessary to implement the approach presented in the Disposal Criticality Analysis Methodology Topical Report and provide calculations utilizing the methodology. Thus, the governing procedure for this type of report is AP-3.12Q, ''Design Calculations and Analyses''. The ''Criticality Model'' is of this latter type, providing a process evaluating the criticality potential of in-package and external configurations. The purpose of this analysis is to layout the process for calculating the criticality potential for various in-package and external configurations and to calculate lower-bound tolerance limit (LBTL) values and determine range of applicability (ROA) parameters. The LBTL calculations and the ROA determinations are performed using selected benchmark experiments that are applicable to various waste forms and various in-package and external configurations. The waste forms considered in this calculation are pressurized water reactor (PWR), boiling water reactor (BWR), Fast Flux Test Facility (FFTF), Training Research Isotope General Atomic (TRIGA), Enrico Fermi, Shippingport pressurized water reactor, Shippingport light water breeder reactor (LWBR), N-Reactor, Melt and Dilute, and Fort Saint Vrain Reactor spent nuclear fuel (SNF). The scope of this analysis is to document the criticality computational method. The criticality

  19. Critical Care

    MedlinePlus

    Critical care helps people with life-threatening injuries and illnesses. It might treat problems such as complications from surgery, accidents, infections, and severe breathing problems. It involves ...

  20. Direct Revascularization With the Angiosome Concept for Lower Limb Ischemia: A Systematic Review and Meta-Analysis.

    PubMed

    Huang, Tzu-Yen; Huang, Ting-Shuo; Wang, Yao-Chang; Huang, Pin-Fu; Yu, Hsiu-Chin; Yeh, Chi-Hsiao

    2015-08-01

    The angiosome concept provides practical information regarding the vascular anatomy of reconstructive and vascular surgery for the treatment of peripheral arterial occlusive disease and, particularly, critical lower limb ischemia.The aim of the study was to confirm the efficacy of direct revascularization with the angiosome concept (DR) for lower limb ischemia.Complementary manual searches were performed through the Pubmed, Cochrane Library, and EMBASE databases.We searched all randomized and nonrandomized studies (NRSs) comparing DR with indirect revascularization (IR) (without the angiosome concept) for lower limb ischemia. Only 9 nonrandomized controlled retrospective cohort studies were found and included. Trials published in any language were included.Primary endpoints were time to limb amputation and time to wound healing. Data extraction and trial quality assessment were performed by two authors independently. A third author was consulted for disagreements settlement and quality assurance.Five NRSs involving 779 lower limbs revealed that DR significantly improved the overall survival of limbs (hazard ratio [HR] 0.61; 95% confidence interval [CI] = 0.46-0.80; P < 0.001; I = 0%). In addition, DR significantly improved time to wound healing (HR 1.38; 95% CI = 1.13-1.69; P = 0.002; I = 0%, in 5 studies including 605 limbs).All included studies were retrospective comparative studies, and no consensus was obtained in describing wound conditions in the included studies.Our results suggested that treatment of lower limb ischemia using DR is more effective in salvaging limbs and healing wounds than IR is. Additional randomized controlled studies are necessary to confirm these results. PMID:26313796

  1. Tissue kallikrein is required for the cardioprotective effect of cyclosporin A in myocardial ischemia in the mouse.

    PubMed

    Youcef, G; Belaidi, E; Waeckel, L; Fazal, L; Clemessy, M; Vincent, M P; Zadigue, G; Richer, C; Alhenc-Gelas, F; Ovize, M; Pizard, A

    2015-03-01

    Clinical and experimental studies suggest that pharmacological postconditioning with Cyclosporin A (CsA) reduces infarct size in cardiac ischemia and reperfusion. CsA interacts with Cyclophilin D (CypD) preventing opening of the mitochondrial permeability transition pore (mPTP). Tissue kallikrein (TK) and its products kinins are involved in cardioprotection in ischemia. CypD knockout mice are resistant to the cardioprotective effects of both CsA and kinins suggesting common mechanisms of action. Using TK gene knockout mice, we investigated whether the kallikrein-kinin system is involved in the cardioprotective effect of CsA. Homozygote and heterozygote TK deficient mice (TK(-/-), TK(+/-)) and wild type littermates (TK(+/+)) were subjected to cardiac ischemia-reperfusion with and without CsA postconditioning. CsA reduced infarct size in TK(+/+) mice but had no effect in TK(+/-) and TK(-/-) mice. Cardiac mitochondria isolated from TK(-/-) mice had indistinguishable basal oxidative phosphorylation and calcium retention capacity compared to TK(+/+) mice but were resistant to CsA inhibition of mPTP opening. TK activity was documented in mouse heart and rat cardiomyoblasts mitochondria. By proximity ligation assay TK was found in close proximity to the mitochondrial membrane proteins VDAC and Tom22, and CypD. Thus, partial or total deficiency in TK induces resistance to the infarct size reducing effect of CsA in cardiac ischemia in mice, suggesting that TK level is a critical factor for cardioprotection by CsA. TK is required for the mitochondrial action of CsA and may interact with CypD. Genetic variability in TK activity has been documented in man and may influence the cardioprotective effect of CsA. PMID:25623731

  2. Endogenous nitric oxide and myocardial adaptation to ischemia.

    PubMed

    Heusch, G; Post, H; Michel, M C; Kelm, M; Schulz, R

    2000-07-21

    Ischemic myocardium does not inevitably undergo necrosis but rather can survive through downregulation of contractile function, ie, "hibernate." To study the role of endogenous NO in this adaptation, 41 enflurane-anesthetized swine were subjected to 90 minutes of moderate left anterior descending coronary artery hypoperfusion and assigned to placebo (P), to 30 mg/kg N(G)-nitro-L-arginine (L-NNA) IV to inhibit NO synthase, or to aortic constriction (AO) to match the increased left ventricular pressure observed with L-NNA. During normoperfusion, a regional myocardial external work index (WI, mm Hg. mm, sonomicrometry and micromanometry) was reduced with L-NNA (from 326+/-27 [SEM] to 250+/-19, P<0.05) but increased with AO (from 321+/-16 to 363+/-19, P<0.05 versus L-NNA). At 10 minutes of ischemia, WI was lower with L-NNA (109+/-10, P<0.05) than P (180+/-22) and AO (170+/-11) and did not change further at 85 minutes of ischemia. Relationships between WI and transmural myocardial blood flow and oxygen consumption were shifted rightward by L-NNA versus P and AO at both 10 and 85 minutes of ischemia. The maximal increment in calcium-activated external work was not different during normoperfusion among groups but was decreased during ischemia with L-NNA. L-NNA transiently increased myocardial contractile calcium sensitivity along with systemic pressure but reduced it during ongoing ischemia. The free-energy change of ATP hydrolysis after an early ischemic decrease recovered toward baseline values in all groups, and necrosis was absent after 2 (triphenyltetrazolium chloride staining) or 8 (histology) hours of reperfusion. Thus, endogenous NO contributes to hibernation by reducing oxygen consumption and preserving calcium sensitivity and contractile function without an energy cost during ischemia. PMID:10903999

  3. Metabolomic markers for intestinal ischemia in a mouse model

    PubMed Central

    Fahrner, René; Beyoğlu, Diren; Beldi, Guido; Idle, Jeffrey R.

    2013-01-01

    Background Diagnosis of intestinal ischemia remains a clinical challenge. The aim of the present study was to use a metabolomic protocol to identify upregulated and downregulated small molecules (Mr < 500) in the serum of mice with intestinal ischemia. Such molecules could have clinical utility when evaluated as biomarkers in human studies. Methods A mouse model for intestinal ischemia was established and validated using histology and serum tumor necrosis factor α concentrations. A second mouse model of peritoneal sepsis was used as a positive control. Serial serum samples were collected from these and from sham-operated animals. Sera were analyzed by gas chromatography–mass spectrometry for 40 small molecules as their trimethylsilyl and O-methyloxime derivatives. Peak areas were normalized against an internal standard and resultant peak area ratios subjected to multivariate data analysis using unsupervised principal components analysis and supervised orthogonal projection to latent structures–discriminant analysis. Upregulated and downregulated serum molecules were identified from their correlation to the orthogonal projection to latent structures–discriminant analysis model. Results Three highly significantly upregulated (fold-change) serum molecules in intestinal ischemia were inorganic phosphate (2.4), urea (4.3), and threonic acid (2.9). Five highly significantly downregulated (fold-change) serum molecules were stearic acid (1.7), arabinose (2.7), xylose (1.6), glucose (1.4), and ribose (2.2). Lactic acid remained unchanged in intestinal ischemia. Conclusions Distinct molecular changes are reported here for the first time in intestinal ischemia. They reveal impairments of gut microbiota metabolism, intestinal absorption, and renal function, together with increased oxidative stress. In contrast to other reports, lactic acid was not significantly changed. These molecular signatures may now be evaluated in clinical studies. PMID:22947700

  4. Hepatic Ischemia and Reperfusion Injury and Trauma: Current Concepts

    PubMed Central

    Papadopoulos, Dimitrios; Siempis, Thomas; Theodorakou, Eleni; Tsoulfas, Georgios

    2013-01-01

    Context Ischemia-reperfusion injury is a fascinating topic which has drawn a lot of interest in the last several years. Hepatic ischemia reperfusion injury may occur in a variety of clinical situations. These include transplantation, liver resection, trauma, and vascular surgery. Evidence Acquisition The purpose of this review was to outline the molecular mechanisms underlying hepatic I/R injury and present the latest approaches, both surgical and pharmacological, regarding the prevention of it. A comprehensive electronic literature search in MEDLINE/PubMed was performed to identify relative articles published within the last 2 years. Results The basic mechanism of hepatic ischemia – reperfusion injury is one of blood deprivation during ischemia, followed by the return of flow during reperfusion. It involves a complex series of events, such as mitochondrial deenergization, adenosine-5'-triphosphate depletion, alterations of electrolyte homeostasis, as well as Kupffer cell activation, oxidative stress changes and upregulation of proinflammatory cytokine signaling. The great number of variable pathways, with several mediators interacting with each other, leads to a high number of candidates for potential therapeutic intervention. As far as surgical approaches are concerned, the modification of existing clamping techniques and the ischemic preconditioning are the most promising techniques till recently. In the search for novel techniques of protecting against hepatic ischemia reperfusion injury, many different strategies have been used in experimental models. The biggest part of this research lies around antioxidant therapy, but other potential solutions have been explored as well. Conclusions The management of hepatic trauma, in spite of the fact that it has become increasingly nonoperative, there still remains the possibility of hepatic resection in the hepatic trauma setting, especially in severe injuries. Hence, clinicians should be familiar with the concept of

  5. Angina and Mental Stress-Induced Myocardial Ischemia

    PubMed Central

    Pimple, Pratik; Shah, Amit J.; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon; Ibeanu, Ijeoma; Raggi, Paolo; Vaccarino, Viola

    2015-01-01

    Objective Mental stress-induced myocardial ischemia is a common phenomenon in patients with coronary artery disease (CAD) and an emerging prognostic factor. Mental stress ischemia is correlated with ambulatory ischemia. However, whether it is related to angina symptoms during daily life has not been examined. Methods We assessed angina-frequency (past month) in 98 post-myocardial infarction (MI) subjects (age 18-60 years) using the Seattle Angina Questionnaire. Patients underwent [99mTc]sestamibi SPECT perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed-difference score (SDS), the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. Results The mean age was 50 years, 50% were female and 60% were non-white. After adjustment for age, sex, smoking, CAD-severity, depressive, anger and anxiety symptoms, each 1-point increase in mental-stress SDS was associated with 1.73-unit increase in the angina-frequency score (95% CI: 0.09-3.37) and 17% higher odds of being in a higher angina-frequency category (OR: 1.17, 95% CI: 1.00-1.38). Depressive symptoms were associated with 12% higher odds of being in a higher angina-frequency category (OR: 1.12, 95% CI: 1.03-1.21). In contrast, exercise/pharmacological stress-induced SDS was not associated with angina-frequency. Conclusion Among young and middle-aged post-MI patients, myocardial ischemia induced by mental stress in the lab, but not by exercise/pharmacological stress, is associated with higher frequency of retrospectively reported angina during the day. Psychosocial stressors related to mental stress ischemia may be important contributory factor to daily angina. PMID:25727240

  6. Extracorporeal Free Flap Perfusion in Case of Prolonged Ischemia Time

    PubMed Central

    Präbst, K.; Beier, J. P.; Meyer, A.; Horch, R. E.

    2016-01-01

    Summary: In free flap surgery, a clinically established concept still has to be found for the reduction of ischemia-related cell damage in the case of prolonged ischemia. Although promising results using extracorporeal free flap perfusion in the laboratory have been published in the past, until now this concept has not yet paved its way into clinical routine. This might be due to the complexity of perfusion systems and a lack of standardized tools. Here, we want to present the results of the first extracorporeal free flap perfusion in a clinical setting using a simple approach without the application of a complex perfusion machinery. PMID:27200244

  7. Critical Muralism

    ERIC Educational Resources Information Center

    Rosette, Arturo

    2009-01-01

    This study focuses on the development and practices of Critical Muralists--community-educator-artist-leader-activists--and situates these specifically in relation to the Mexican mural tradition of los Tres Grandes and in relation to the history of public art more generally. The study examines how Critical Muralists address artistic and…

  8. Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

    PubMed Central

    Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

    2015-01-01

    The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia. PMID:26807119

  9. pH-Controlled Hydrogen Sulfide Release for Myocardial Ischemia-Reperfusion Injury.

    PubMed

    Kang, Jianming; Li, Zhen; Organ, Chelsea L; Park, Chung-Min; Yang, Chun-Tao; Pacheco, Armando; Wang, Difei; Lefer, David J; Xian, Ming

    2016-05-25

    Hydrogen sulfide (H2S) is a critical signaling molecule that regulates many physiological and/or pathological processes. Modulation of H2S levels could have potential therapeutic value. In this work, we report the rational design, synthesis, and biological evaluation of a class of phosphonamidothioate-based H2S-releasing agents (i.e., H2S donors). A novel pH-dependent intramolecular cyclization was employed to promote H2S release from the donors. These water-soluble compounds showed slow, controllable, and pH-sensitive production of H2S in aqueous solutions. The donors also showed significant cytoprotective effects in cellular models of oxidative damage. Most importantly, the donors were found to exhibit potent cardioprotective effects in an in vivo murine model of myocardial ischemia-reperfusion (MI/R) injury through a H2S-related mechanism. PMID:27172143

  10. Ultrasound enhanced thrombolysis in acute arterial ischemia.

    PubMed

    Tsivgoulis, Georgios; Culp, William C; Alexandrov, Andrei V

    2008-08-01

    In vitro and animal studies have shown that thrombolysis with intravenous tissue plasminogen activator (tPA) can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. Moreover, intravenous gaseous microspheres with ultrasound have been shown to be a potential alternative to fibrinolytic agents to recanalize discrete peripheral thrombotic arterial occlusions or acute arteriovenous graft thromboses. Small phase I-II randomized and non-randomized clinical trials have shown promising results concerning the potential applications of ultrasound-enhanced thrombolysis in the setting of acute cerebral ischemia. CLOTBUST was an international four-center phase II trial, which demonstrated that, in patients with acute ischemic stroke, transcranial Doppler (TCD) monitoring augments tPA-induced arterial recanalization (sustained complete recanalization rates: 38% vs. 13%) with a non-significant trend toward an increased rate of clinical recovery from stroke, as compared with placebo. The rates of symptomatic intracerebral hemorrhage (sICH) were similar in the active and placebo group (4.8% vs. 4.8%). Smaller single-center clinical trials using transcranial color-coded sonography (TCCD) reported recanalization rates ranging from 27% to 64% and sICH rates of 0-18%. A separate clinical trial evaluating the safety and efficacy of therapeutic low-frequency ultrasound was discontinued because of a concerning sICH rate of 36% in the active group. To further enhance the ability of tPA to break up thrombi, current ongoing clinical trials include phase II studies of a single beam 2 MHz TCD with perflutren-lipid microspheres. Moreover, potential enhancement of intra-arterial tPA delivery is being clinically tested with 1.7-2.1 MHz pulsed wave ultrasound (EKOS catheter) in ongoing phase II-III clinical trials. Intravenous platelet-targeted microbubbles with low-frequency ultrasound are currently

  11. Gangrene in Takayasu's arteritis: a report of two cases and review of literature.

    PubMed

    Misra, Durga Prasanna; Chowdhury, Abhra Chandra; Lal, Hira; Mohindra, Namita; Agarwal, Vikas

    2016-03-01

    Takayasu's arteritis (TA) is a granulomatous large vessel vasculitis more commonly seen in India. The vascular inflammation in TA results in stenoses of affected vessels. Usually this is a slow process with good collateral circulation; only rarely does critical limb ischemia result. We present two patients of TA who presented with gangrene of extremities, and review eight prior such patients reported in the literature. With appropriate diagnosis and treatment with oral corticosteroids and low-dose aspirin, none of our patients had recurrence at a mean follow-up of 3.8 ± 2.8 years. Although rare, TA can present with gangrene and rheumatologists need to be aware of this unusual but limb-threatening manifestation of TA to institute appropriate therapy in a timely manner. PMID:26563339

  12. Critics and Criticism of Education

    ERIC Educational Resources Information Center

    Ornstein, Allan C.

    1977-01-01

    Radical educational critics, such as Edgar Friedenberg, Paul Goodman, A. S. Neill, John Holt, Jonathan Kozol, Herbert Kohl, James Herndon, and Ivan Illich, have few constructive goals, no strategy for broad change, and a disdain for modernization and compromise. Additionally, these critics, says the author, fail to consider social factors related…

  13. Angina and exertional myocardial ischemia in diabetic and nondiabetic patients: assessment by exercise thallium scintigraphy

    SciTech Connect

    Nesto, R.W.; Phillips, R.T.; Kett, K.G.; Hill, T.; Perper, E.; Young, E.; Leland, O.S. Jr.

    1988-02-01

    Patients with diabetes mellitus and coronary artery disease are thought to have painless myocardial ischemia more often than patients without diabetes. We studied 50 consecutive patients with diabetes and 50 consecutive patients without diabetes, all with ischemia, on exercise thallium scintigraphy to show the reliability of angina as a marker for exertional ischemia. The two groups had similar clinical characteristics, treadmill test results, and extent of infarction and ischemia, but only 7 patients with diabetes compared with 17 patients without diabetes had angina during exertional ischemia. In diabetic patients the extent of retinopathy, nephropathy, or peripheral neuropathy was similar in patients with and without angina. Angina is an unreliable index of myocardial ischemia in diabetic patients with coronary artery disease. Given the increased cardiac morbidity and mortality in such patients, periodic objective assessments of the extent of ischemia are warranted.

  14. Ligustrazine monomer against cerebral ischemia/reperfusion injury.

    PubMed

    Gao, Hai-Jun; Liu, Peng-Fei; Li, Pei-Wen; Huang, Zhuo-Yan; Yu, Feng-Bo; Lei, Ting; Chen, Yong; Cheng, Ye; Mu, Qing-Chun; Huang, Hai-Yan

    2015-05-01

    Ligustrazine (2,3,5,6-tetramethylpyrazine) is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mechanism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administration, and the most effective mode of administration for clinical treatment of cerebral ischemia/reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine administration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[(1,1-dimethylethyl)oxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC195 after cerebral ischemia were better than ligustrazine. PMID:26109963

  15. Brain polyphosphoinositide metabolism during focal ischemia in rat cortex

    SciTech Connect

    Lin, T.N.; Liu, T.H.; Xu, J.; Hsu, C.Y.; Sun, G.Y. )

    1991-04-01

    Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting {sup 32}Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when {sup 32}Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.

  16. The chemokine system in arteriogenesis and hind limb ischemia.

    PubMed

    Shireman, Paula K

    2007-06-01

    Chemokines (chemotactic cytokines) are important in the recruitment of leukocytes to injured tissues and, as such, play a pivotal role in arteriogenesis and the tissue response to ischemia. Hind limb ischemia represents a complex model with arteriogenesis (collateral artery formation) occurring in tissues with normal perfusion while areas exhibiting ischemic necrosis undergo angiogenesis and skeletal muscle regeneration; monocytes and macrophages play an important role in all three of these processes. In addition to leukocyte trafficking, chemokines are produced by and chemokine receptors are present on diverse cell types, including myoblasts, endothelial, and smooth muscle cells. Thus, the chemokine system may have direct effects as well as inflammatory-mediated effects on arteriogenesis, angiogenesis, and skeletal muscle regeneration. This article reviews the complexity of the hind limb ischemia model and the role of the chemokine system in arteriogenesis and the tissue response to ischemia. Special emphasis will be placed on the roles of monocytes/macrophages and CCL2/monocyte chemotactic protein-1 (MCP-1) in these processes. PMID:17544024

  17. Energy Drinks and Myocardial Ischemia: A Review of Case Reports.

    PubMed

    Lippi, Giuseppe; Cervellin, Gianfranco; Sanchis-Gomar, Fabian

    2016-07-01

    The use and abuse of energy drinks (EDs) is constantly increasing worldwide. We performed a systematic search in Medline, Scopus and Web of Science to identify evidence about the potential link between these beverages and myocardial ischemia. Overall, 8 case reports could be detected, all of which described a realistic association between large intake of EDs and episodes of myocardial ischemia. Interestingly, no additional triggers of myocardial ischemia other than energy drinks could be identified in the vast majority of cases. Some plausible explanations can be brought in support of this association. Most of the biological effects of EDs are seemingly mediated by a positive inotropic effect on cardiac function, which entails increase in heart rate, cardiac output and contractility, stroke volume and arterial blood pressure. Additional biological abnormalities reported after EDs intake include increased platelet aggregation, endothelial dysfunction, hyperglycemia as well as an increase in total cholesterol, triglycerides and low-density lipoprotein cholesterol. Although a causal relationship between large consumption of EDs and myocardial ischemia cannot be definitely established so far, concerns about the cardiovascular risk of excessive consumption of these beverages are seemingly justified. PMID:26320007

  18. Tumor Cold Ischemia - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    In a recently published manuscript in the journal of Molecular and Cellular Proteomics, researchers from the National Cancer Institutes (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigated the effect of cold ischemia on the proteome of fresh frozen tumors.

  19. Identification of exercise-induced ischemia using QRS slopes.

    PubMed

    Firoozabadi, Reza; Gregg, Richard E; Babaeizadeh, Saeed

    2016-01-01

    In this work we studied a computer-aided approach using QRS slopes as unconventional ECG features to identify the exercise-induced ischemia during exercise stress testing and demonstrated that the performance is comparable to the experts' manual analysis using standard criteria involving ST-segment depression. We evaluated the performance of our algorithm using a database including 927 patients undergoing exercise stress tests and simultaneously collecting the ECG recordings and SPECT results. High resolution 12-lead ECG recordings were collected continuously throughout the rest, exercise, and recovery phases. Patients in the database were classified into three categories of moderate/severe ischemia, mild ischemia, and normal according to the differences in sum of the individual segment scores for the rest and stress SPECT images. Philips DXL 16-lead diagnostic algorithm was run on all 10-s segments of 12-lead ECG recordings for each patient to acquire the representative beats, ECG fiducial points from the representative beats, and other ECG parameters. The QRS slopes were extracted for each lead from the averaged representative beats and the leads with highest classification power were selected. We employed linear discriminant analysis and measured the performance using 10-fold cross-validation. Comparable performance of this method to the conventional ST-segment analysis exhibits the classification power of QRS slopes as unconventional ECG parameters contributing to improved identification of exercise-induced ischemia. PMID:26607407

  20. Oxidative and inflammatory biomarkers of ischemia and reperfusion injuries.

    PubMed

    Halladin, Natalie Løvland

    2015-04-01

    Ischemia-reperfusion injuries occur when the blood supply to an organ or tissue is temporarily cut-off and then restored. Even though the restoration of blood flow is absolutely essential in preventing tissue death, the reperfusion of oxygenated blood to the oxygen-deprived areas may in itself augment the tissue damage in excess of that produced by the ischemia alone. The process of ischemia-reperfusion is multifactorial and there are several mechanisms involved in the pathogenesis. Ample evidence shows that the injury is in part caused by an excessive generation of reactive oxygen species or free radicals. The free radicals consequently initiate an inflammatory response, which in some cases may affect distant organs, thus causing remote organ injuries. Ischemia-reperfusion injuries are a common complication in many diseases (acute myocardial infarctions, stroke) or surgical settings (transplantations, tourniquet-related surgery) and they have potential detrimental and disabling consequences. The tolerance of ischemia-reperfusion has proven to be time-of-day-dependent and the size of myocardial infarctions has proven to be significantly higher when occurring in the dark-to-light period. This period is characterized by and coincides with a rapid decrease in the plasma levels of the hormone melatonin. Melatonin is the body's most potent antioxidant and is capable of both direct free radical scavenging and indirect optimization of other anti-oxidant enzymes. It also possesses anti-inflammatory properties and is known to inhibit the mitochondrial permeability transition pore during reperfusion. This inhibiting property has been shown to be of great importance in reducing ischemia-reperfusion injuries. Furthermore, melatonin is a relatively non-toxic molecule, which has proven to be safe for use in clinical trials. Thus, there is compelling evidence of melatonin's effect in reducing ischemia-reperfusion injuries in many experimental studies, but the number of human

  1. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines

    PubMed Central

    Warrington, Junie P

    2015-01-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ∼13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R2 = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  2. Magnesium sulfate protects fetal skin from intrauterine ischemia reperfusion injury.

    PubMed

    Kaptanoglu, Asli F; Arca, Turkan; Kilinc, Kamer

    2012-09-01

    Intrauterine ischemia-reperfusion (I/R) injury in fetus occurs with multifactorial pathogenesis and results with multiorgan injury including skin. Magnesium has widespread use in obstetric practice. Inn addition to magnesium's tocolytic and neuroprotective properties, it also has free radical reducing effects. The aim of the present study was to demonstrate whether magnesium sulfate could have protective effect on fetal rat skin in intrauterine ischemia-reperfusion (I/R) injury. Fetal skin ischemia was induced by clamping the utero-ovarian arteries bilaterally for 30 min, and reperfusion was achieved by removing the clamps for 60 min in 19-day pregnant rats. Magnesium Sulfate (MgSO(4)) was given to pregnant rats 20 min before I/R injury at the dose of 600 mg/kg in magnesium treatment group. No ischemia reperfusion was applied to control and sham-operated groups. Lipid peroxidation from the skin tissues was determined as thiobarbituric acid reactive substances (TBARS). Myeloperoxidase (MPO) activity was determined for neutrophil activation. The results showed that the levels of TBARS and MPO increased significantly in the fetal rat skin after I/R injury compared to control group. Levels of TBARS and MPO were significantly lower than those of I/R group in Magnesium-treated group. In conclusion, intrauterine ischemia-reperfusion may produce considerable fetal skin injury. Increased TBARS and MPO activity can be inhibited by magnesium treatment. This suggests that magnesium treatment may have protective effect on fetal rat skin in intrauterine I/R injury. PMID:22310734

  3. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    PubMed

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. PMID:26831193

  4. Microcirculatory, mitochondrial, and histological changes following cerebral ischemia in swine

    PubMed Central

    2014-01-01

    Background Ischemic brain injury due to stroke and/or cardiac arrest is a major health issue in modern society requiring urgent development of new effective therapies. The aim of this study was to evaluate mitochondrial, microcirculatory, and histological changes in a swine model of global cerebral ischemia. Results In our model, significant microcirculatory changes, but only negligible histological cell alterations, were observed 3 h after bilateral carotid occlusion, and were more pronounced if the vascular occlusion was combined with systemic hypotension. Analysis of mitochondrial function showed that LEAK respiration (measured in the presence of pyruvate + malate but without ADP) was not affected in any model of global cerebral ischemia in pigs. The OXPHOS capacity with pyruvate + malate as substrates decreased compared with the control levels after bilateral carotid artery occlusion, and bilateral carotid artery occlusion + hypotension by 20% and 79%, respectively, resulting in decreases in the respiratory control index of 14% and 73%, respectively. OXPHOS capacity with succinate as a substrate remained constant after unilateral carotid artery occlusion or bilateral carotid artery occlusion, but decreased by 53% after bilateral carotid artery occlusion and hypotension compared with controls (p < 0.05, n = 3–6). Addition of exogenous cytochrome c to mitochondria isolated from ischemia brains had no effect on respiration in all models used in this study. Conclusions We found a decrease in microcirculation and mitochondrial oxidative phosphorylation activity, but insignificant neuronal death, after 3 h ischemia in all our pig models of global cerebral ischemia. Dysfunction of the mitochondrial oxidative phosphorylation system, particularly damage to complex I of the respiratory chain, may be the primary target of the ischemic insult, and occurs before signs of neuronal death can be detected. PMID:24387285

  5. Early markers for myocardial ischemia and sudden cardiac death.

    PubMed

    Sabatasso, Sara; Mangin, Patrice; Fracasso, Tony; Moretti, Milena; Docquier, Mylène; Djonov, Valentin

    2016-09-01

    The post-mortem diagnosis of acute myocardial ischemia remains a challenge for both clinical and forensic pathologists. We performed an experimental study (ligation of left anterior descending coronary artery in rats) in order to identify early markers of myocardial ischemia, to further apply to forensic and clinical pathology in cases of sudden cardiac death. Using immunohistochemistry, Western blots, and gene expression analyses, we investigated a number of markers, selected among those which are currently used in emergency departments to diagnose myocardial infarction and those which are under investigation in basic research and autopsy pathology studies on cardiovascular diseases. The study was performed on 44 adult male Lewis rats, assigned to three experimental groups: control, sham-operated, and operated. The durations of ischemia ranged between 5 min and 24 h. The investigated markers were troponins I and T, myoglobin, fibronectin, C5b-9, connexin 43 (dephosphorylated), JunB, cytochrome c, and TUNEL staining. The earliest expressions (≤30 min) were observed for connexin 43, JunB, and cytochrome c, followed by fibronectin (≤1 h), myoglobin (≤1 h), troponins I and T (≤1 h), TUNEL (≤1 h), and C5b-9 (≤2 h). By this investigation, we identified a panel of true early markers of myocardial ischemia and delineated their temporal evolution in expression by employing new technologies for gene expression analysis, in addition to traditional and routine methods (such as histology and immunohistochemistry). Moreover, for the first time in the autopsy pathology field, we identified, by immunohistochemistry, two very early markers of myocardial ischemia: dephosphorylated connexin 43 and JunB. PMID:27392959

  6. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines.

    PubMed

    Warrington, Junie P

    2015-11-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ~13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R(2) = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  7. Time-dependent Gene Profiling Indicates the Presence of Different Phases for Ischemia/Reperfusion Injury in Retina

    PubMed Central

    Andreeva, Kalina; Zhang, Meixia; Fan, Wei; Li, Xiaohong; Chen, Yinlu; Rebolledo-Mendez, Jovan D; Cooper, Nigel G

    2014-01-01

    Ischemia/reperfusion (IR) injury has been associated with several retinal pathologies, and a few genes/gene products have been linked to IR injury. However, the big picture of temporal changes, regarding the affected gene networks, pathways, and processes remains to be determined. The purpose of the present study was to investigate initial, intermediate, and later stages to characterize the etiology of IR injury in terms of the pathways affected over time. Analyses indicated that at the initial stage, 0-hour reperfusion following the ischemic period, the ischemia-associated genes were related to changes in metabolism. In contrast, at the 24-hour time point, the signature events in reperfusion injury include enhanced inflammatory and immune responses as well as cell death indicating that this would be a critical period for the development of any interventional therapeutic strategies. Genes in the signal transduction pathways, particularly transmitter receptors, are downregulated at this time. Activation of the complement system pathway clearly plays an important role in the later stages of reperfusion injury. Together, these results demonstrate that the etiology of injury related to IR is characterized by the appearance of specific patterns of gene expression at any given time point during retinal IR injury. These results indicate that evaluation of treatment strategies with respect to time is very critical. PMID:25210480

  8. Lipopolysaccharide Pretreatment Protects from Renal Ischemia/Reperfusion Injury

    PubMed Central

    Heemann, Uwe; Szabo, Attila; Hamar, Peter; Müller, Veronika; Witzke, Oliver; Lutz, Jens; Philipp, Thomas

    2000-01-01

    In vivo administration of low doses of lipopolysaccharide (LPS) to rodents can protect these animals from subsequently administrated, usually lethal doses of endotoxin or LPS. In this study we tested the effects of LPS pretreatment on ischemia/reperfusion injury in the kidney. Male C57/B1 mice were pretreated with different doses of LPS or phosphate-buffered saline on days −4 and −3. The right kidney was removed, and the vessels of the left kidney were clamped for 30 or 45 minutes on day 0. Creatinine levels and survival of animals were monitored. To test the involvement of cytokines, additional animals were harvested before (“time 0”) and 15 minutes, 1, 2, 8, and 16 hours after reperfusion for histology, immunohistochemistry, terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay, and reverse transcriptase-polymerase chain reaction analysis (including tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, inducible nitric oxide synthase (iNOS), and interferon (IFN)-γ messenger RNA (mRNA)). In controls, renal ischemia of 30 minutes was nonlethal, whereas 73% of the animals died within 48 ± 18 hours, after 45 minutes of ischemia. All different doses of LPS protected the animals from lethal renal ischemia/reperfusion injury. Starting at similar levels, serum creatinine increased significantly in controls but not in LPS-pretreated animals over time. As early as 2 hours after reperfusion, tubular cell damage was significantly more pronounced in controls than in LPS-treated mice. In controls, tubules deteriorated progressively until 8 hours of reperfusion. At this time, more than 50% of tubular cells were destroyed. This destruction was accompanied by a pronounced leukocytic infiltration, predominantly by macrophages. In contrast, LPS pretreatment prevented the destruction of kidney tissue and infiltration by leukocytes. The terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay revealed significantly more apoptotic cells in

  9. Overactivation of the nuclear factor (erythroid-derived 2)-like 2-antioxidant response element pathway in hepatocytes decreases hepatic ischemia/reperfusion injury in mice.

    PubMed

    Lee, Lung-Yi; Harberg, Calvin; Matkowskyj, Kristina A; Cook, Shelly; Roenneburg, Drew; Werner, Sabine; Johnson, Jeffrey; Foley, David P

    2016-01-01

    Hepatic ischemia/reperfusion injury (IRI) is a critical component of hepatic surgery. Oxidative stress has long been implicated as a key player in IRI. In this study, we examine the cell-specific role of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-antioxidant response element pathway in warm hepatic IRI. Nrf2 knockout (KO) and wild-type (WT) animals and novel transgenic mice expressing a constitutively active nuclear factor (erythroid-derived 2)-like 2 (caNrf2) mutant in hepatocytes (AlbCre+/caNrf2+) and their littermate controls underwent partial hepatic ischemia or sham surgery. The animals were killed 6 hours after reperfusion, and their serum and tissue were collected for analysis. As compared to WT animals after ischemia/reperfusion (IR), Nrf2 KO mice had increased hepatocellular injury with increased serum alanine aminotransferase and aspartate aminotransferase, Suzuki score, apoptosis, an increased inflammatory infiltrate, and enhanced inflammatory cytokine expression. On the other hand, AlbCre+/caNrf2+ that underwent IR had significantly reduced serum transaminases, less necrosis on histology, and a less pronounced inflammatory infiltrate and inflammatory cytokine expression as compared to the littermate controls. However, there were no differences in apoptosis. Taken together, Nrf2 plays a critical role in our murine model of warm hepatic IRI, with Nrf2 deficiency exacerbating hepatic IRI and hepatocyte-specific Nrf2 overactivation providing protection against warm hepatic IRI. PMID:26285140

  10. Critical Thinking

    ERIC Educational Resources Information Center

    Villano, Matt

    2006-01-01

    True excellence in technology implementation emerges when IT, administrative, and academic leaders link IT to mission-critical institutional objectives, investing in hardware and software to serve an explicit purpose and a distinct population of users. This article illustrates that at public institutions of higher education in New Hampshire as…

  11. WNT AGONIST DECREASES TISSUE DAMAGE AND IMPROVES RENAL FUNCTION AFTER ISCHEMIA-REPERFUSION

    PubMed Central

    Kuncewitch, Michael; Yang, Weng-Lang; Corbo, Lana; Khader, Adam; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

    2014-01-01

    Renal ischemia-reperfusion (IR) injury (IRI) following shock states or transplantation causes tissue damage and delayed graft function, respectively. The Wnt/β-catenin signaling pathway plays a critical role in nephrogenesis. We therefore hypothesized that pharmacological activation of Wnt/β-catenin signaling by Wnt agonist, a synthetic pyrimidine, could protect kidneys from IRI. Adult male rats were subjected to bilateral clamping of the renal pedicles with microvascular clips for 60 min, followed by reperfusion. Wnt agonist (5 mg/kg BW) or vehicle (20% DMSO in saline) was administered intravenously 1 h prior to ischemia. Blood and renal tissues were collected 24 h after IR for evaluation. Renal IR caused a significant reduction of β-catenin and its downstream target gene cyclin D1 by 65% and 39%, respectively, compared to the sham, while Wnt agonist restored them to the sham levels. The number and intensity of cells staining with the proliferation marker Ki67 in ischematized kidneys were enhanced by Wnt agonist. The integrity of the renal histological architecture in the Wnt agonist group was better preserved than the vehicle group. Wnt agonist significantly lowered serum levels of creatinine, AST, and LDH, inhibited the production of IL-6 and IL-1β, and MPO activities. Lastly, Wnt agonist reduced iNOS, nitrotyrosine proteins and 4-hydroxynonenal in the kidneys by 60%, 47% and 21%, respectively, compared to the vehicle. These results indicate that Wnt agonist improves renal regeneration and function while attenuating inflammation and oxidative stress in the kidneys after IR. Thus, pharmacologic stimulation of Wnt/β-catenin signaling provides a beneficial effect on the prevention of renal IRI. PMID:25514428

  12. One of the most urgent vascular circumstances: Acute limb ischemia

    PubMed Central

    Sahin, Muslum; Kirma, Cevat

    2013-01-01

    Acute limb ischemia is a sudden decrease in limb perfusion that threatens limb viability and requires urgent evaluation and management. Most of the causes of acute limb ischemia are thrombosis of a limb artery or bypass graft, embolism from the heart or a disease artery, dissection, and trauma. Assessment determines whether the limb is viable or irreversibly damaged. Prompt diagnosis and revascularization by means of catheter-based thrombolysis or thrombectomy and by surgery reduce the risk of limb loss and mortality. Amputation is performed in patients with irreversible damage. Despite urgent revascularization, amputation rate is 10%–15% in patients during hospitalization, mostly above the knee, and mortality within 1 year is 10%–15% due to the coexisting conditions. PMID:26770694

  13. Achieving zero ischemia in minimally invasive partial nephrectomy surgery.

    PubMed

    Hou, Weibin; Ji, Zhigang

    2015-06-01

    Widespread application of the minimally invasive partial nephrectomy (MIPN) techniques like laparoscopic and robotic partial nephrectomy, has been limited by concerns about prolonged warm ischemia. So techniques aiming at performing have been actively explored. A systemic review of literatures on the MIPN without hilar clamping was performed and related methods were summarized. There are mainly seven methods including selective/segmental renal artery clamping technique, selective renal parenchymal clamping technique, targeted renal blood flow interruption technique, laser supported MIPN, radio frequency assisted MIPN, hydro-jet assisted MIPN, and sequential preplaced suture renorrhaphy technique that have been undergoing enthusiastic investigation for achieving MINP without hilar clamping. All of these emerging techniques represent the exploring work to achieve a zero ischemia MIPN for small renal tumors of different characteristics. Though not perfect for any of the technique, they deserve a further assessment during their future experimental and clinical applications. PMID:25895732

  14. Multi-modality Optical Imaging of Rat Kidney Dysfunction: In Vivo Response to Various Ischemia Times.

    PubMed

    Ding, Zhenyang; Jin, Lily; Wang, Hsing-Wen; Tang, Qinggong; Guo, Hengchang; Chen, Yu

    2016-01-01

    We observed in vivo kidney dysfunction with various ischemia times at 30, 75, 90, and 120 min using multi-modality optical imaging: optical coherence tomography (OCT), Doppler OCT (DOCT), and two-photon microscopy (TPM). We imaged the renal tubule lumens and glomerulus at several areas of each kidney before, during, and after ischemia of 5-month-old female Munich-Wistar rats. For animals with 30 and 75 min ischemia times, we observed that all areas were recovered after ischemia, that tubule lumens were re-opened and the blood flow of the glomerulus was re-established. For animals with 90 and 120 min ischemia times, we observed unrecovered areas, and that tubule lumens remained close after ischemia. TPM imaging verified the results of OCT and provided higher resolution images than OCT to visualize renal tubule lumens and glomerulus blood flow at the cellular level. PMID:27526162

  15. A New Approach: Regional Nerve Blockade for Angioplasty of the Lower Limb

    SciTech Connect

    Marcus, A.J. Lotzof, K.; Kamath, B.S.K.; Shanthakumar, R.E.; Munir, N.; Loh, A.; Bird, R.; Howard, A.

    2006-04-15

    Purpose. An audit study investigated the pilot use of regional nerve block analgesia (as an alternative to sedative/opiate, general or central neuraxial anesthesia) performed by radiologists with the assistance of imaging techniques during complex prolonged angiography. Methods. Radiologists were trained by anesthetic consultants to administer and use lower limb peripheral nerve block for difficult prolonged angioplasty procedures for patients with severe lower limb rest pain who were unable to lie in the supine position. In a pilot study 25 patients with limb-threatening ischemia received sciatic and femoral nerve blockade for angioplasty. The technique was developed and perfected in 12 patients and in a subsequent 13 patients the details of the angiography procedures, peripheral anesthesia, supplementary analgesia, complications, and pain assessment scores were recorded. Pain scores were also recorded in 11 patients prior to epidural/spinal anesthesia for critical ischemic leg angioplasty. Results. All patients with peripheral nerve blockade experienced a reduction in their ischemic rest pain to a level that permitted angioplasty techniques to be performed without spinal, epidural or general analgesia. In patients undergoing complex angioplasty intervention, the mean pain score by visual analogue scale was 3.7, out of a maximum score of 10. Conclusions. The successful use of peripheral nerve blocks was safe and effective as an alternative to sedative/opiate, epidural or general anesthesia in patients undergoing complex angiography and has optimized the use of radiological and anesthetic department resources. This has permitted the frequent radiological treatment of patients with limb-threatening ischemia and reduced delays caused by the difficulty in enlisting the help of anesthetists, often at short notice, from the busy operating lists.

  16. Insights Into Microcirculation Underlying Critical Limb Ischemia by Single-Photon Emission Computed Tomography

    PubMed Central

    Liu, Jung-Tung; Chang, Cheng-Siu; Su, Chen-Hsing; Li, Cho-Shun

    2015-01-01

    Abstract Perfusion difference is used as a parameter to evaluate microcirculation. This study aims to differentiate lower-limb perfusion insufficiency from neuropathy to prevent possible occurrence of failed back surgery syndrome (FBSS). Patients were retrospectively gathered from 134 FBSS cases diagnosed in the past 7 years. Up to 82 cases that were excluded from neuralgia by radiologic imaging, electrodiagnostic electromyography, and nerve conduction velocity were enrolled in this study. Perfusion difference was evaluated by single-photon emission computed tomography, and pain intensities were recorded via visual analog scale (VAS) score. Lower perfusion at the left leg comprises 51.2% (42 of 82) of the patients. The mean perfusion difference of the 82 patients was 0.86 ± 0.05 (range: 0.75–0.93). Patients with systemic vascular diseases exhibited significantly higher perfusion difference than that of patients without these related diseases (P < 0.05), except for renal insufficiency (P = 0.134). Significant correlation was observed between perfusion difference and VAS score (r = −0.78; P < 0.0001; n = 82). In this study, we presented perfusion difference as a parameter for evaluating microcirculation, which cannot be detected by ultrasonography or angiography. PMID:26166084

  17. Critical Limb Ischemia in Association with Charcot Neuroarthropathy: Complex Endovascular Therapy for Limb Salvage

    SciTech Connect

    Palena, Luis Mariano; Brocco, Enrico; Manzi, Marco

    2013-05-09

    Charcot neuroarthropathy is a low-incidence complication of diabetic foot and is associated with ankle and hind foot deformity. Patients who have not developed deep ulcers are managed with offloading and supportive bracing or orthopedic arthrodesis. In patients who have developed ulcers and severe ankle instability and deformity, below-the-knee amputation is often indicated, especially when deformity and cutaneous involvement result in osteomyelitis. Ischemic association has not been described but can be present as a part of peripheral arterial disease in the diabetic population. In this extreme and advanced stage of combined neuroischemic diabetic foot disease, revascularization strategies can support surgical and orthopedic therapy, thus preventing osteomyelitis and leading to limb and foot salvage.

  18. Fatal subarachnoid hemorrhage following ischemia in vertebrobasilar dolichoectasia.

    PubMed

    Sokolov, Arseny A; Husain, Shakir; Sztajzel, Roman; Croquelois, Alexandre; Lobrinus, Johannes A; Thaler, David; Städler, Claudio; Hungerbühler, Hansjörg; Caso, Valeria; Rinkel, Gabriel J; Michel, Patrik

    2016-07-01

    Vertebrobasilar dolichoectasia (VBD) is a chronic disorder with various cerebrovascular and compressive manifestations, involving subarachnoid hemorrhage (SAH). Occurrence of SAH shortly after worsening of clinical VBD symptoms has occasionally been reported. The goal of the study was to examine this association, in particular its pathophysiology, clinical precursor signs, time course, and outcome.To this end, in a retrospective multicenter study, we analyzed 20 patients with VBD and SAH in regard to preceding clinical symptoms, presence of vertebrobasilar thrombosis and ischemia, outcome and neuropathological correlates.Median age of the 7 female and 13 male patients was 70 years (interquartile range [IQR] 18.3 years). Fourteen patients (70%) presented with new or acutely worsening posterior fossa signs at a median of 3 days prior to SAH (IQR 2, range 0.5-14). A thrombus within the VBD was detected in 12 patients (60%). Thrombus formation was associated with clinical deterioration (χ = 4.38, P = 0.04) and ponto-cerebellar ischemia (χ = 8.09, P = 0.005). During follow-up after SAH, 13 patients (65%) died, after a median survival time of 24 hours (IQR 66.2, range 2-264 hours), with a significant association between proven ponto-cerebellar ischemia and case fatality (χ = 6.24, P = 0.01).The data establish an association between clinical deterioration in patients with VBD, vertebrobasilar ischemia, and subsequent SAH. Antithrombotic treatment after deterioration appears controversial and SAH outcome is frequently fatal. Our data also indicate a short window of 3 days that may allow for evaluating interventional treatment, preferably within randomized trials. PMID:27399083

  19. Pentoxifylline in ischemia-induced acute kidney injury in rats.

    PubMed

    Okumura, Alice S; Rodrigues, Luiz Erlon; Martinelli, Reinaldo

    2009-01-01

    Ischemia is an important cause of acute kidney injury (AKI). Pentoxifylline has been shown to improve tissue oxygenation and endothelial function and inhibit proinflammatory cytokine production. The aim of this study was to evaluate a possible renal protective effect of pentoxifylline against ischemia by measuring mitochondrial respiratory metabolism as an index of cell damage. Rats were submitted to right nephrectomy. The left kidney was submitted to ischemia by clamping the renal artery for 45 minutes. Immediately after release of the clamp, 1 mL of a solution containing 20 mg of pentoxifylline/mL was injected intravenously, while a control group received 1 mL of normal saline intravenously. Five minutes after the injection, the left kidney was removed, homogenized, and subjected to refrigerated differential centrifugation. Mitochondrial respiratory metabolism was measured polarographically. The mitochondria isolated from the kidneys of saline-treated rats had an endogenous respiration of 9.20 +/- 1.0 etamol O(2)/mg protein/min compared to 8.9 +/- 1.4 etamol O(2)/mg protein/min in the pentoxifylline-treated rats (p > 0.05). When stimulated by sodium succinate, the respiratory metabolism increased in a similar fashion in both groups of animals: 17.9 +/- 2.3 and 18.1 +/- 2.1 etamol O(2)/mg protein/min in the untreated and pentoxifylline-treated groups, respectively (p > 0.05). In the present study, pentoxifylline was not found to exert any protective effect on the kidney. It is possible that at the time of pentoxifylline administration, the mitochondria had already been damaged by the process of ischemia, and its effect may have been insufficient to reverse cell damage. PMID:19925292

  20. Effectiveness of sugammadex for cerebral ischemia/reperfusion injury.

    PubMed

    Ozbilgin, Sule; Yılmaz, Osman; Ergur, Bekir Ugur; Hancı, Volkan; Ozbal, Seda; Yurtlu, Serhan; Gunenc, Sakize Ferim; Kuvaki, Bahar; Kucuk, Burcu Ataseven; Sisman, Ali Rıza

    2016-06-01

    Cerebral ischemia may cause permanent brain damage and behavioral dysfunction. The efficacy and mechanisms of pharmacological treatments administered immediately after cerebral damage are not fully known. Sugammadex is a licensed medication. As other cyclodextrins have not passed the necessary phase tests, trade preparations are not available, whereas sugammadex is frequently used in clinical anesthetic practice. Previous studies have not clearly described the effects of the cyclodextrin family on cerebral ischemia/reperfusion (I/R) damage. The aim of this study was to determine whether sugammadex had a neuroprotective effect against transient global cerebral ischemia. Animals were assigned to control, sham-operated, S 16 and S 100 groups. Transient global cerebral ischemia was induced by 10-minute occlusion of the bilateral common carotid artery, followed by 24-hour reperfusion. At the end of the experiment, neurological behavior scoring was performed on the rats, followed by evaluation of histomorphological and biochemical measurements. Sugammadex 16 mg/kg and 100 mg/kg improved neurological outcome, which was associated with reductions in both histological and neurological scores. The hippocampus TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase results in the S 16 and S 100 treatment groups were significantly lower than those of the I/R group. Neurological scores in the treated groups were significantly higher than those of the I/R group. The study showed that treatment with 16 mg/kg and 100 mg/kg sugammadex had a neuroprotective effect in a transient global cerebral I/R rat model. However, 100 mg/kg sugammadex was more neuroprotective in rats. PMID:27377841

  1. Role of cytokines in myocardial ischemia and reperfusion.

    PubMed

    Sharma, H S; Das, D K

    1997-01-01

    Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia-reperfusion injury. Furthermore, ischemia-reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-alpha) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart. PMID:18472818

  2. Aspergillus fumigatus Invasion Increases with Progressive Airway Ischemia

    PubMed Central

    Hsu, Joe L.; Khan, Mohammad A.; Sobel, Raymond A.; Jiang, Xinguo; Clemons, Karl V.; Nguyen, Tom T.; Stevens, David A.; Martinez, Marife; Nicolls, Mark R.

    2013-01-01

    Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould’s angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80%) for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections. PMID:24155924

  3. [Effect of occlusive cerebral ischemia on functional status of the internal organs].

    PubMed

    Molchanova, L V; Chernobaeva, G N; Shcherbakova, L N; Luk'ianova, L D

    2001-01-01

    Biochemical parameters characterizing visceral functions were measured in the plasma of rats with brain ischemia induced by double occlusion of the carotid arteries. Functional insufficiency of the viscera is gradually forming in the course of occlusive ischemia of the brain. Functional insufficiency of the liver was observed in animals with severe neurological deficiency and subsequent lethal outcome. In rats resistant to ischemia, visceral dysfunctions develop in a certain succession, starting from the pancreas and followed by the myocardium, liver, and kidneys. PMID:11855065

  4. Mesenteric ischemia masquerading as refractory peritonitis in continuous ambulatory peritoneal dialysis patients.

    PubMed

    Vishwakarma, K; Anandh, U

    2015-01-01

    We report two cases of mesenteric ischemia in patients on long term peritoneal dialysis both of which were associated with poor outcomes. Both were diabetic and on peritoneal dialysis for a long time. On evaluation of refractory peritonitis we found evidence of non occlusive mesenteric ischemia. Despite adequate treatment both succumbed to their illness. Abdominal pathology, especially mesenteric ischemia leading to gut infarction, should be considered in patients with refractory peritonitis. PMID:26664217

  5. The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

    2015-01-01

    Objective The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Methods Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Conclusion Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future. PMID:26113960

  6. Diffractomery analysis of human and rat erythrocytes deformability under ischemia

    NASA Astrophysics Data System (ADS)

    Lugovtsov, Andrei E.; Priezzhev, Alexander V.; Nikitin, Sergei Y.; Koshelev, Vladimir B.

    2007-07-01

    In this work, the analysis of human and rat red blood cells (RBC) deformability, internal viscosity and yield stress of RBC in norm and ischemia was performed by means of laser diffractometry - a modern technique allowing for measuring the flexibility of RBC, which determines the blood flow parameters in vessels. Ischemic diseases of people and animals are accompanied with deterioration of microrheologic properties of their blood, in particular, with impairing the RBC deformability. Human RBCs were obtained from the blood of healthy individuals and from patients suffering from ischemic diseases. The RBC deformability indices from both groups of individuals were measured. Rat RBCs were obtained from a control group of animals and from a group with experimentally induced ischemia (EII). This animal model is frequently used for studying the response of an organism to ischemia. The effect of semax, a medication that is frequently used for therapeutic treatments of human brain diseases in clinical practice, on RBC deformability was studied with its application in vitro and in vivo. It is shown that in human ischemic patients, the deformability index of RBC was lower than that from healthy individuals. Both in vivo and in vitro applied semax positively influences the impaired deformability properties of RBCs of ischemic rats.

  7. Endovascular Treatment of Chronic Mesenteric Ischemia: Report of Five Cases

    SciTech Connect

    Nyman, Ulf; Ivancev, Krasnodar; Lindh, Mats; Uher, Petr

    1998-07-15

    Purpose: To evaluate the midterm results of percutaneous transluminal angioplasty (PTA) and stent placement in stenotic and occluded mesenteric arteries in five consecutive patients with chronic mesenteric ischemia. Methods: Five patients with 70%-100% obliterations of all mesenteric vessels resulting in chronic mesenteric ischemia (n= 4) and as a prophylactic measure prior to abdominal aortic aneurysm repair (n= 1) underwent PTA of celiac and/or superior mesenteric artery (SMA) stenoses (n= 2), primary stenting of ostial celiac occlusions (n= 2), and secondary stenting of a SMA occlusion (n= 1; recoil after initial PTA). All patients underwent duplex ultrasonography (US) (n= 3) and/or angiography (n= 5) during a median follow-up of 21 months (range 8-42 months). Results: Clinical success was obtained in all five patients. Asymptomatic significant late restenoses (n3) were successfully treated with repeat PTA (n= 2) and stenting of an SMA occlusion (n= 1; celiac stent restenosis). Recurrent pain in one patient was interpreted as secondary to postsurgical abdominal adhesions. Two puncture-site complications occurred requiring local surgical treatment. Conclusions: Endovascular techniques may be attempted prior to surgery in cases of stenotic or short occlusive lesions in patients with chronic mesenteric ischemia. Surgery may still be preferred in patients with long occlusions and a low operative risk.

  8. Celiac axis stenosis and lethal liver ischemia after pancreaticoduodenectomy.

    PubMed

    Lipska, Ludmila; Visokai, Vladimir; Levy, Miroslav; Koznar, Boris; Zaruba, Pavel

    2009-01-01

    Celiac axis stenosis can lead to a fatal hepatic ischemia after pancreaticoduodenectomy unless a simultaneous revascularisation of the celiac circulation is performed. In the present study are reported three cases of celiac axis stenosis, all of which had histologically confirmed periampullary cancer. Case 1: a 50-year-old male with a history of myocardial infarction and liver steatosis; visceral arteriography prior to the surgery demonstrated a celiac axis stenosis. Whipple operation was performed. After removing the specimen, no signs of liver ischemia were found (liver was cholestatic) and pulsation of the hepatic artery was strong. The patient died on the second postoperative day after an abrupt irreversible cardiac arrest. Autopsy proved acute severe hepatic ischemia. Case 2: a 64-year-old female. Preoperative visceral angiography showed significant celiac axis stenosis. As a first step of surgery the root of the celiac trunk was exposed, a fibrotic ring around it was divided. Standard D1 pylorus preserving pancreaticoduodenectomy was performed. Case 3: a 58-year-old female without preoperative angiography, indicated for surgery. After an occlusion test of the gastroduodenal artery the liver became ischemic. Division of the fibrotic ring around celiac axis was performed together with a standard D1 pylorus preserving pancreaticoduodenectomy. No postoperative complications were reported in both case 2 and 3. PMID:19760970

  9. Pentoxifylline attenuates reperfusion injury in skeletal muscle after partial ischemia.

    PubMed

    Kishi, M; Tanaka, H; Seiyama, A; Takaoka, M; Matsuoka, T; Yoshioka, T; Sugimoto, H

    1998-05-01

    Leukocytes have been shown to contribute to ischemia-reperfusion injury in skeletal muscle. Pentoxifylline (PTXF), a xanthine-derived phosphodiesterase inhibitor, has received recent attention because of its action on leukocytes. To clarify the effects of PTXF in reperfusion injury, we measured the resting transmembrane potential difference (Em) and evaluated postcapillary venule microcirculation using intravital microscopy in rat skeletal muscle during ischemia and reperfusion. The infrarenal aorta was clamped for 90 min and then reperfused for 60 min. Persistent depolarization of the resting Em was observed in an ischemia-reperfusion (IR) group and was significantly repolarized in a PTXF group during the reperfusion period. The tissue water content was significantly reduced in the PTXF group, although no difference was noted in the tissue lactate content. Flowing erythrocyte velocity and wall shear rate in the PTXF group were significantly higher than in the IR group during the reperfusion period but without significant differences in vessel diameter and hemoglobin oxygenation. Blood flow measured by laser-Doppler flowmeter was also significantly improved in the PTXF group. Furthermore, the adherent leukocyte count was significantly reduced in the PTXF group during this same period. These results indicate that PTXF attenuated reperfusion-associated membrane injury and tissue edema and that PTXF suppressed leukocyte adhesion and improved hindlimb blood flow during the reperfusion period. PMID:9612347

  10. Transluminal coronary angioplasty in the treatment of silent ischemia

    SciTech Connect

    Bergin, P.; Myler, R.K.; Shaw, R.E.; Stertzer, S.H.; Clark, D.A.; Ryan, C.; Murphy, M.C.

    1988-01-01

    Fifty-four asymptomatic patients with positive thallium exercise tests underwent coronary angiography followed by coronary angioplasty (PTCA), as the primary therapy for silent ischemia. The procedure was technically successful in 89% of these patients. Emergency bypass graft surgery was necessary in 2 (3.6%) and q-wave myocardial infarction occurred in 1 (1.8%) of these. All fifty-four patients have been followed for a mean of 35 months since angioplasty. Of the 48 patients with initially successful PTCA, 12 had either clinical restenosis (9/14 or 19%) or a new lesion (3/48 or 6%) during follow-up, which required a repeat PTCA. At the longest follow-up, 46 (85%) had been successfully treated with on or more PTCA procedures. Two patients (3.6%) had sustained late q-wave myocardial infarction and two additional patients reported angina pectoris. There were no deaths. Angioplasty as a primary therapy for silent ischemia appears efficacious, with success and restenosis rates comparable to those in the symptomatic population. Event-free survival is improved, compared with natural history data for patients with silent ischemia from other studies. Prudent risk/benefit analysis may help to define subgroups most likely to benefit from this intervention.

  11. Functional muscle ischemia in Duchenne and Becker muscular dystrophy

    PubMed Central

    Thomas, Gail D.

    2013-01-01

    Duchenne and Becker muscular dystrophy (DMD/BMD) comprise a spectrum of devastating X-linked muscle wasting disease for which there is no treatment. DMD/BMD is caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that stabilizes the muscle membrane and also targets other proteins to the sarcolemma. Among these is the muscle-specific isoform of neuronal nitric oxide synthase (nNOSμ) which binds spectrin-like repeats within dystrophin's rod domain and the adaptor protein α-syntrophin. Dystrophin deficiency causes loss of sarcolemmal nNOSμ and reduces paracrine signaling of muscle-derived nitric oxide (NO) to the microvasculature, which renders the diseased muscle fibers susceptible to functional muscle ischemia during exercise. Repeated bouts of functional ischemia superimposed on muscle fibers already weakened by dystrophin deficiency result in use-dependent focal muscle injury. Genetic and pharmacologic strategies to boost nNOSμ-NO signaling in dystrophic muscle alleviate functional muscle ischemia and show promise as novel therapeutic interventions for the treatment of DMD/BMD. PMID:24391598

  12. [Transesophageal atrial stimulation--a test for myocardial ischemia].

    PubMed

    Jović, A; Nekić-Borcilo, M; Troskot, R; Nekić, D; Knezević, A; Rados, G

    1994-01-01

    The aim of the present study was to determine clinical value and the feasibility of transesophageal atrial pacing (TAP) in diagnosing myocardial ischemia in patients with coronary artery disease (CAD). Forty patients with CAD and with significant ST-segment depression in a standard 12-lead ECG during bicycle-stress testing underwent TAP. Rapid atrial stimulation was performed by using a very flexible six-polar polyurethane pacing lead introduced through the nares into the esophagus and connected to the stimulator allowing selection of rate, output voltage and pulse duration. The satisfactory atrial pacing was obtained by 28 +/- 6 V output and 7 +/- 1 ms pulse duration. Of 40 patients who underwent TAP, ischemic ECG changes were induced in 35 (u = 2,24 p < 0,05) and were very similar to those that occurred during bicycle-stress testing according to their intensity and distribution and affected ECG leads with comparable peak rate-pressure products. This suggests comparable sensitivity of TAP and bicycle-stress testing in discovering myocardial ischemia in CAD patients. Four patients had negative test for myocardial ischemia and in one TAP was discontinued because of intolerable chest discomfort. In conclusion, TAP is a reliable alternative technique for the assessment of coronary artery disease. In combination with some other noninvasive methods (echocardiography, scintigraphy, i.v. digital angiography), it has become a routine diagnostic procedure in cardiac patients. PMID:8028438

  13. Free radical metabolites in myocardium during ischemia and reperfusion.

    PubMed

    Ruuge, E K; Ledenev, A N; Lakomkin, V L; Konstantinov, A A; Ksenzenko MYu

    1991-10-01

    Low-temperature electron paramagnetic resonance (EPR) spectroscopy and spin traps were used to measure paramagnetic species generation in rat hearts and isolated mitochondria. The hearts were freeze-clamped at 77 K during control perfusion by the Langendorff procedure, after 20-30 min of normothermic ischemia or 10-30 s of reperfusion with oxygenated perfusate. All EPR spectra measured at 4.5-50 K exhibited signals of both mitochondrial free radical centers and FeS proteins. The analysis of spectral parameters measured at 243 K showed that free radicals in heart tissue were semiquinones of coenzyme Q10 and flavins. The appearance of a typical "doublet" signal at g = 1.99 in low-temperature spectra indicated that a part of ubisemiquinones formed a complex with a high potential FeS protein of succinate dehydrogenase. Ischemia decreased the free radical species in myocardium approximately 50%; the initiation of reflow of perfusate resulted in quick increase of the EPR signal. Mitochondria isolated from hearts during control perfusion and after 20-30 min of ischemia were able to produce superoxide radicals in both the NADH-coenzyme Q10 reductase and the bc1 segments of the respiratory chain. The rate of oxyradical generation was significantly higher in mitochondria isolated from ischemic heart. PMID:1656795

  14. Selective platelet deposition during focal cerebral ischemia in the monkey

    SciTech Connect

    Feinberg, H.; Crowell, R.M.; Jafar, J.J.; Marmo, F.; Gandhi, Y.; Mosher, J.L.; Le Breton, G.C.

    1986-03-01

    Platelet thrombosis in the microcirculation may play a central role in focal cerebral ischemia. The authors investigated platelet deposition after temporary middle cerebral artery (MCA) occlusion in the monkey. Anesthetized monkeys were infused with autologous /sup 111/In-labeled platelets and /sup 51/Cr-labeled red cells in order to measure platelet deposition independent of hemorrhage. The right MCA was occluded for 6 hrs with a clip via a trans-orbital approach. Following clip removal, reperfusion was carried out for 45 min after which the animal was sacrificed. Brain samples were assayed for platelet deposition in selected areas of the right and left hemispheres (RH, LH). Net platelet deposition was determined from the excess /sup 111/In counts above that contained in blood (as determined by /sup 51/Cr counts). It was found that ischemia resulted in selective platelet deposition in the area of the occluded MCA, i.e. the RH versus the corresponding areas in the LH. Differences between the RH and the LH were found in the (1) caudate nucleus, (2) internal capsule and (3) putamen. The data suggest that focal ischemia is associated with the activation of platelets in the ischemic area.

  15. Apperceptive signals demonstrating the dynamic disturbance of myocardial ischemia.

    PubMed

    Moulder, P V; Flauto, B; Gallet, B; Galansky, S; Alexander, J A

    1979-01-01

    Analog pressure signals (catheter-tip manometers) from the left atrium, left ventricle, and aorta and a flow signal from the arota were obtained in 25, open-chest, anesthetized dogs in which 115 episodes of ischemia were produced in an area of the left ventricle subtended by the distal left anterior descending coronary artery and its last major diagonal branch. The left ventricular pressure and its first derivative (dP/dt) were displayed as an X-Y loop. The character of this loop went through a unique series of dynamic changes in 110 of the 115 ischemic episodes, indicating that this is a useful tool for monitoring myocardial ischemia. Spectrum pairs of the above signals were analyzed with digital computational transfer functions in 14 ischemic episodes of three experiments and preliminary assessment reveals unique pole and zero changes in many pairs during each episode which also may prove to be a useful indicator of the hemodynamic disturbance incurred during myocardial ischemia. PMID:758716

  16. Dynamic reactive astrocytes after focal ischemia

    PubMed Central

    Ding, Shinghua

    2014-01-01

    Astrocytes are specialized and most numerous glial cell type in the central nervous system and play important roles in physiology. Astrocytes are also critically involved in many neural disorders including focal ischemic stroke, a leading cause of brain injury and human death. One of the prominent pathological features of focal ischemic stroke is reactive astrogliosis and glial scar formation associated with morphological changes and proliferation. This review paper discusses the recent advances in spatial and temporal dynamics of morphology and proliferation of reactive astrocytes after ischemic stroke based on results from experimental animal studies. As reactive astrocytes exhibit stem cell-like properties, knowledge of dynamics of reactive astrocytes and glial scar formation will provide important insights for astrocyte-based cell therapy in stroke. PMID:25657720

  17. Transitory Ischemia as a form of white torture: a case description in Spain.

    PubMed

    Pérez-Sales, Pau; Fernández-Liria, Alberto; Parras, Marina; Engst, Gina

    2010-01-01

    Transitory Ischemia is a form of torture that has been insufficiently described and studied in forensic and psychiatric studies of torture. It is usually left out of medical evaluation reports and not explored in detail under the Istanbul Protocol. Although ischemia, when experienced during brief periods of time, does not produce any detectable sequelae, prolonged periods of ischemia can be detected by either clinical examination or electromyography. The authors describe the use of brief periods of ischemia as a torture technique against a non-violent activist in Seville (Spain). PMID:20952826

  18. Effect of lidocaine on left ventricular pressure-volume curves during demand ischemia in pigs.

    PubMed

    Tayama, M; Solomon, S B; Glantz, S A

    1998-06-01

    The diastolic pressure-volume curve shifts upward during demand ischemia, most likely because of changes in Ca2+ dynamics within the sarcomere. It is possible that agents that affect Na+/Ca2+ exchange, such as lidocaine, a class 1b-type Na+-channel blocker that decreases intracellular Na+, could affect the diastolic pressure-volume relationship because of indirect effects on intracellular Ca2+. Lidocaine is a drug widely used to treat arrhythmias in patients with myocardial ischemia. We studied the effects of lidocaine on diastolic dysfunction associated with demand ischemia. We compared diastolic (as represented by the shift in the diastolic pressure-volume relationship) and systolic function during demand ischemia before and after lidocaine injection. We created demand ischemia in pigs before and after administering lidocaine (5 mg/kg) in eight open-pericardium anesthetized pigs. Demand ischemia was induced by constricting the left anterior descending coronary artery and then pacing at 1.5-1.8 times the baseline heart rate for 1.5-3 min. Hemodynamics were recorded during baseline, demand ischemia, baseline after lidocaine injection, and demand ischemia after lidocaine. Lidocaine did not affect systolic function or the time constant of isovolumic relaxation, but it increased the upward shift of the diastolic pressure-volume curve during demand ischemia compared with the increase that occurred before lidocaine was administered. This result suggests that lidocaine could aggravate diastolic dysfunction in patients with ischemic heart disease. PMID:9841537

  19. Expression of neuron specific phosphatase, striatal enriched phosphatase (STEP) in reactive astrocytes after transient forebrain ischemia.

    PubMed

    Hasegawa, S; Morioka, M; Goto, S; Korematsu, K; Okamura, A; Yano, S; Kai, Y; Hamada, J I; Ushio, Y

    2000-02-15

    We studied the distribution and change of striatal enriched phosphatase (STEP) in the gerbil hippocampus after transient forebrain ischemia. STEP was expressed in the perikarya and in neuronal processes; it was not detected in non-neuronal cells of control animals. After 5-min forebrain ischemia, STEP immunoreactivity (STEP-IR) was preserved for 2 days; it disappeared 4 and more days after ischemia with completion of delayed neuronal death (DND) in the CA1 subfield. Furthermore, only in the CA1 after ischemia, STEP was expressed in reactive astrocytes for 4 to 28 days, showing different patterns of glial fibrillary acidic protein (GFAP)-positive reactive astrocytes. After non-or less-than lethal ischemia, STEP expression in reactive astrocytes corresponded with the degree of neuronal degeneration. Immunoblot analysis of the CA1 subfield revealed the expression of three isoforms, STEP45, -56 and -61; their expression patterns changed with time after ischemia. These data suggest that neuronal STEP is preserved until cell degeneration after ischemia and that STEP is expressed in reactive astrocytes only after lethal ischemia, with different expression patterns for its isoforms. Of STEP45, -56 and -61, STEP61 was the most strongly expressed in the reactive astrocytes; both STEP45 and -61 were expressed in neurons and the expression of STEP56 was weak. STEP may play an important role not only in neurons but also in reactive astrocytes after ischemia, depending on neuronal degeneration. PMID:10652442

  20. Preconditioning ischemia time determines the degree of glycogen depletion and infarct size reduction in rat hearts.

    PubMed

    Barbosa, V; Sievers, R E; Zaugg, C E; Wolfe, C L

    1996-02-01

    The cardioprotective effect of preconditioning is associated with glycogen depletion and attenuation of intracellular acidosis during subsequent prolonged ischemia. This study determined the effects of increasing preconditioning ischemia time on myocardial glycogen depletion and on infarct size reduction. In addition, this study determined whether infarct size reduction by preconditioning correlates with glycogen depletion before prolonged ischemia. Anesthetized rats underwent a single episode of preconditioning lasting 1.25, 2.5, 5, or 10 minutes or multiple episodes cumulating in 10 (2 x 5 min) or 20 minutes (4 x 5 or 2 x 10 min) of preconditioning ischemia time, each followed by 5 minutes of reperfusion. Then both preconditioned and control rats underwent 45 minutes of ischemia induced by left coronary artery (LCA) occlusion and 120 minutes of reperfusion. After prolonged ischemia, infarct size was determined by dual staining with triphenyltetrazolium chloride and phthalocyanine blue dye. Glycogen levels were determined by an enzymatic assay in selected rats from each group before prolonged ischemia. We found that increasing preconditioning ischemia time resulted in glycogen depletion and infarct size reduction that could both be described by exponential functions. Furthermore, infarct size reduction correlated with glycogen depletion before prolonged ischemia (r = 0.98; p < 0.01). These findings suggest a role for glycogen depletion in reducing ischemic injury in the preconditioned heart. PMID:8579012

  1. Carnosine pretreatment protects against hypoxia-ischemia brain damage in the neonatal rat model.

    PubMed

    Zhang, Xiangmin; Song, Lili; Cheng, Xiuyong; Yang, Yi; Luan, Bin; Jia, Liting; Xu, Falin; Zhang, Zhan

    2011-09-30

    Perinatal hypoxia-ischemia brain injury is a major cause of mortality and morbidity in neonates and lacks an effective treatment thus far. Carnosine has been demonstrated to play a neuroprotective role in the adult brain injuries. However, there is no information available concerning its neuroprotective role in the immature brains after hypoxia-ischemia insults. Therefore, we investigated whether carnosine could also confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. Hypoxia-ischemia was induced in rats on postnatal day 7 (P7). Carnosine (250 mg/kg) was administered intraperitoneally, 30 min prior to hypoxia-ischemia induction. Morphological brain injury and biochemical markers of apoptosis and oxidative stress were evaluated 24 h after hypoxia-ischemia induction. Cognitive performance was evaluated by the Morris Water Maze test on P28-P33. We found that pretreatment with carnosine significantly reduced the infarct volume and the number of terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hypoxia-ischemia brain. Carnosine also inhibited mRNA expression of apoptosis-inducing factor(AIF) and caspase-3, which was accompanied by an increase in superoxide dismutase(SOD)activity and a decrease in the malondialdehyde(MDA)level in carnosine-treated rats. Furthermore, carnosine also improved the spatial learning and memory abilities of rats declined due to hypoxia-ischemia. These results demonstrate that carnosine can protect rats against hypoxia-ischemia-induced brain damage by antioxidation. PMID:21693116

  2. Effect of Cyperus rotundus on ischemia-induced brain damage and memory dysfunction in rats

    PubMed Central

    Dabaghian, Fataneh Hashem; Hashemi, Mehrdad; Entezari, Maliheh; Movassaghi, Shabnam; Goushegir, Seyed Ashrafadin; Kalantari, Samaneh; Movafagh, Abolfazl; Sharifi, Zahra Nadia

    2015-01-01

    Objective(s): Global cerebral ischemia-reperfusion injury causes loss of pyramidal cells in CA1 region of hippocampus. In this study, we investigated the possible neuroprotective effects of the ethanol extract of Cyperus rotundus (EECR) on a model of global transient ischemia in rat, by evaluating the pathophysiology of the hippocampal tissue and spatial memory. Materials and Methods: Treatment group (EECR, 100 mg/kg/day) was gavaged from 4 days before, to 3 days after ischemia. Morris water maze test was performed 1 week after ischemia for 4 days. Brain tissue was prepared for Nissl staining. Results: Our data showed no statistical difference between the treatment and ischemia groups in water maze task. So, treatment of ischemia with EECR cannot improve spatial learning and memory. On the contrary EECR ameliorated the CA1 pyramidal cell loss due to transient global ischemia/reperfusion injury. Conclusion: These results suggest that EECR cannot reduce the ischemia-induced, cognitive impairments seen after transient, global cerebral ischemia but can prevent pyramidal cell loss in CA1 region of hippocampus. PMID:25825638

  3. A patient with recent chest discomfort-ischemia or no ischemia? Postsystolic shortening comes to the rescue.

    PubMed

    Fadel, Bahaa M; Al-Amro, Bandar; Al-Admawi, Mohammed; Sergani, Hani; Alsoufi, Bahaaldin; Pergola, Valeria; Di Salvo, Giovanni

    2013-10-01

    The diagnosis of myocardial ischemia in the emergency department can be challenging particularly in a patient in whom the chest discomfort has abated. Symptoms can be atypical, physical exam is often noncontributory, the electrocardiogram is usually nondiagnostic and cardiac enzymes remain normal. Thus, the decision for hospital admission or discharge can be quite difficult. Here, we describe such a patient in whom echocardiography with strain imaging identified the presence of postsystolic shortening (PSS) at the left ventricular apex. This suggested the likelihood of ischemic memory in the territory of the left anterior descending (LAD) artery. At coronary angiography a high grade stenosis was present in the proximal LAD artery. Our report highlights the role of echocardiography in the detection of myocardial ischemia and apical PSS as a marker of ischemic memory. PMID:23822760

  4. Phosphotyrosine signaling analysis in human tumors is confounded by systemic ischemia-driven artifacts and intra-specimen heterogeneity.

    PubMed

    Gajadhar, Aaron S; Johnson, Hannah; Slebos, Robbert J C; Shaddox, Kent; Wiles, Kerry; Washington, Mary Kay; Herline, Alan J; Levine, Douglas A; Liebler, Daniel C; White, Forest M

    2015-04-01

    Tumor protein phosphorylation analysis may provide insight into intracellular signaling networks underlying tumor behavior, revealing diagnostic, prognostic or therapeutic information. Human tumors collected by The Cancer Genome Atlas program potentially offer the opportunity to characterize activated networks driving tumor progression, in parallel with the genetic and transcriptional landscape already documented for these tumors. However, a critical question is whether cellular signaling networks can be reliably analyzed in surgical specimens, where freezing delays and spatial sampling disparities may potentially obscure physiologic signaling. To quantify the extent of these effects, we analyzed the stability of phosphotyrosine (pTyr) sites in ovarian and colon tumors collected under conditions of controlled ischemia and in the context of defined intratumoral sampling. Cold-ischemia produced a rapid, unpredictable, and widespread impact on tumor pTyr networks within 5 minutes of resection, altering up to 50% of pTyr sites by more than 2-fold. Effects on adhesion and migration, inflammatory response, proliferation, and stress response pathways were recapitulated in both ovarian and colon tumors. In addition, sampling of spatially distinct colon tumor biopsies revealed pTyr differences as dramatic as those associated with ischemic times, despite uniform protein expression profiles. Moreover, intratumoral spatial heterogeneity and pTyr dynamic response to ischemia varied dramatically between tumors collected from different patients. Overall, these findings reveal unforeseen phosphorylation complexity, thereby increasing the difficulty of extracting physiologically relevant pTyr signaling networks from archived tissue specimens. In light of this data, prospective tumor pTyr analysis will require appropriate sampling and collection protocols to preserve in vivo signaling features. PMID:25670172

  5. Ion-sensitive field effect transistors for pH and potassium ion concentration sensing: towards detection of myocardial ischemia

    NASA Astrophysics Data System (ADS)

    Rai, Pratyush; Jung, Soyoun; Ji, Taeksoo; Varadan, Vijay K.

    2008-03-01

    Ion Sensitive Field Effect Transistors (ISFETs) for sensing change in ionic concentration in biological systems can be used for detecting critical conditions like Myocardial Ischemia. Having the ability to yield steady signal characteristics can be used to observe the ionic concentration gradients which mark the onset of ischemia. Two ionic concentrations, pH and [K +], have been considered as the indicator for Myocardial Ischemia in this study. The ISFETs in this study have an organic semi-conductor film as the electronically active component. Poly-3 hexylthiophene was chosen for its compatibility to the solution processing, which is a simple and economical method of thin film fabrication. The gate electrode, which regulates the current in the active layer, has been employed as the sensor element. The devices under study here were fabricated on a flexible substrate PEN. The pH sensor was designed with the Tantalum Oxide gate dielectric as the ion selective component. The charge accumulated on the surface of the metal oxide acts as the source of the effecter electric field. The device was tested for pH values between 6.5 and 7.5, which comprises the variation observed during ischemic attack. The potassium ion sensor has got a floating gate electrode which is functionalized to be selective to potassium ion. The device was tested for potassium ion concentration between 5 and 25 mM, which constitutes the variation in extra cellular potassium ion concentration during ischemic attack. The device incorporated a monolayer of Valinomycin, a potassium specific ionophore, on top of the gate electrode.

  6. Pathologic assessment of myocardial cell necrosis and apoptosis after ischemia and reperfusion with molecular and morphological markers.

    PubMed

    Takashi, E; Ashraf, M

    2000-02-01

    The present work illustrates the critical subcellular changes in the rat heart after 10-30 min of left coronary artery (LCA) occlusion and 120 min of reperfusion with a combination of several staining techniques. Triphenyltetrazolium chloride (TTC) to detect non-injured myocytes, horseradish peroxidase (HRP) and terminal deoxynucleotide nick-end labeling (TUNEL) to detect necrotic and apoptotic cells were employed and electron microscopy (EM) was used to validate these changes. After 20 min of LCA occlusion, myocytes began to undergo necrosis whilst after 10 min occlusion, no myocyte underwent irreversible cell injury in the risk area. After 30 min of LCA occlusion and 120 min reperfusion, 36.3, 26.6 and 25% cells were normal, necrotic, and reversibly injured, respectively; the remaining 12.8% cells were apoptotic. Necrotic cells were strongly positive with HRP and negative for TTC and TUNEL. TUNEL-positive or apoptotic cells were slightly HRP-positive, indicating altered cell membrane permeability. Reversibly-injured myocytes were TTC-, HRP- and TUNEL-negative. These changes were more accurately defined in the 100- microm thick sections than in the traditional slices. It is concluded that: (1) TTC-staining of 100- microm thick sections is far superior and accurate for the detection of ischemic changes with shorter period of ischemia (10 min); (2) the combination of TTC-staining, HRP reaction and TUNEL method is excellent for demarcation of early ischemic changes; (3) TTC-negativity in ischemia less than 20 min does not indicate necrosis but only represents reversible changes; (4) the apoptosis is absent in early ischemia of 20 min with or without reperfusion at a time when sufficient ATP is present, and appears only after 30 min of coronary ligation and reperfusion; and (5) the apoptotic cells lose membrane integrity accompanied by decreased glycocalyx thickness and cell swelling as opposed to commonly known characteristics of apoptotic cells. PMID:10722798

  7. Dual AAV therapy ameliorates exercise-induced muscle injury and functional ischemia in murine models of Duchenne muscular dystrophy

    PubMed Central

    Zhang, Yadong; Yue, Yongping; Li, Liang; Hakim, Chady H.; Zhang, Keqing; Thomas, Gail D.; Duan, Dongsheng

    2013-01-01

    Neuronal nitric oxide synthase (nNOS) membrane delocalization contributes to the pathogenesis of Duchenne muscular dystrophy (DMD) by promoting functional muscle ischemia and exacerbating muscle injury during exercise. We have previously shown that supra-physiological expression of nNOS-binding mini-dystrophin restores normal blood flow regulation and prevents functional ischemia in transgenic mdx mice, a DMD model. A critical next issue is whether systemic dual adeno-associated virus (AAV) gene therapy can restore nNOS-binding mini-dystrophin expression and mitigate muscle activity-related functional ischemia and injury. Here, we performed systemic gene transfer in mdx and mdx4cv mice using a pair of dual AAV vectors that expressed a 6 kb nNOS-binding mini-dystrophin gene. Vectors were packaged in tyrosine mutant AAV-9 and co-injected (5 × 1012 viral genome particles/vector/mouse) via the tail vein to 1-month-old dystrophin-null mice. Four months later, we observed 30–50% mini-dystrophin positive myofibers in limb muscles. Treatment ameliorated histopathology, increased muscle force and protected against eccentric contraction-induced injury. Importantly, dual AAV therapy successfully prevented chronic exercise-induced muscle force drop. Doppler hemodynamic assay further showed that therapy attenuated adrenergic vasoconstriction in contracting muscle. Our results suggest that partial transduction can still ameliorate nNOS delocalization-associated functional deficiency. Further evaluation of nNOS binding mini-dystrophin dual AAV vectors is warranted in dystrophic dogs and eventually in human patients. PMID:23681067

  8. Ranolazine, an antianginal agent, markedly reduces ventricular arrhythmias induced by ischemia and ischemia-reperfusion.

    PubMed

    Dhalla, Arvinder K; Wang, Wei-Qun; Dow, Joan; Shryock, John C; Belardinelli, Luiz; Bhandari, Anil; Kloner, Robert A

    2009-11-01

    We tested the effect of the antianginal agent ranolazine on ventricular arrhythmias in an ischemic model using two protocols. In protocol 1, anesthetized rats received either vehicle or ranolazine (10 mg/kg, iv bolus) and were subjected to 5 min of left coronary artery (LCA) occlusion and 5 min of reperfusion with electrocardiogram and blood pressure monitoring. In protocol 2, rats received either vehicle or three doses of ranolazine (iv bolus followed by infusion) and 20 min of LCA occlusion. With protocol 1, ventricular tachycardia (VT) occurred in 9/12 (75%) vehicle-treated rats and 1/11 (9%) ranolazine-treated rats during reperfusion (P = 0.003). Sustained VT occurred in 5/12 (42%) vehicle-treated but 0/11 in ranolazine-treated rats (P = 0.037). The median number of episodes of VT during reperfusion in vehicle and ranolazine groups was 5.5 and 0, respectively (P = 0.0006); median duration of VT was 22.2 and 0 s in vehicle and ranolazine rats, respectively (P = 0.0006). With protocol 2, mortality in the vehicle group was 42 vs. 17% (P = 0.371), 10% (P = 0.162) and 0% (P = 0.0373) with ranolazine at plasma concentrations of 2, 4, and 8 microM, respectively. Ranolazine significantly reduced the incidence of ventricular fibrillation [67% in controls vs. 42% (P = 0.414), 30% (P = 0.198) and 8% (P = 0.0094) in ranolazine at 2, 4, and 8 microM, respectively]. Median number (2.5 vs. 0; P = 0.0431) of sustained VT episodes, incidence of sustained VT (83 vs. 33%, P = 0.0361), and the duration of VT per animal (159 vs. 19 s; P = 0.0410) were also significantly reduced by ranolazine at 8 microM. Ranolazine markedly reduced ischemia-reperfusion induced ventricular arrhythmias. Ranolazine demonstrated promising anti-arrhythmic properties that warrant further investigation. PMID:19767532

  9. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI).

    PubMed

    Mills, Joseph L; Conte, Michael S; Armstrong, David G; Pomposelli, Frank B; Schanzer, Andres; Sidawy, Anton N; Andros, George

    2014-01-01

    Critical limb ischemia, first defined in 1982, was intended to delineate a subgroup of patients with a threatened lower extremity primarily because of chronic ischemia. It was the intent of the original authors that patients with diabetes be excluded or analyzed separately. The Fontaine and Rutherford Systems have been used to classify risk of amputation and likelihood of benefit from revascularization by subcategorizing patients into two groups: ischemic rest pain and tissue loss. Due to demographic shifts over the last 40 years, especially a dramatic rise in the incidence of diabetes mellitus and rapidly expanding techniques of revascularization, it has become increasingly difficult to perform meaningful outcomes analysis for patients with threatened limbs using these existing classification systems. Particularly in patients with diabetes, limb threat is part of a broad disease spectrum. Perfusion is only one determinant of outcome; wound extent and the presence and severity of infection also greatly impact the threat to a limb. Therefore, the Society for Vascular Surgery Lower Extremity Guidelines Committee undertook the task of creating a new classification of the threatened lower extremity that reflects these important considerations. We term this new framework, the Society for Vascular Surgery Lower Extremity Threatened Limb Classification System. Risk stratification is based on three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). The implementation of this classification system is intended to permit more meaningful analysis of outcomes for various forms of therapy in this challenging, but heterogeneous population. PMID:24126108

  10. Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, ...

  11. Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice

    SciTech Connect

    Cao Canxiang; Yang Qingwu . E-mail: yangqwmlys@hotmail.com; Lv Fenglin; Cui Jie; Fu Huabin; Wang Jingzhou

    2007-02-09

    Inflammatory reaction plays an important role in cerebral ischemia-reperfusion injury, however, its mechanism is still unclear. Our study aims to explore the function of Toll-like receptor 4 (TLR4) in the process of cerebral ischemia-reperfusion. We made middle cerebral artery ischemia-reperfusion model in mice with line embolism method. Compared with C3H/OuJ mice, scores of cerebral water content, cerebral infarct size and neurologic impairment in C3H/Hej mice were obviously lower after 6 h ischemia and 24 h reperfusion. Light microscopic and electron microscopic results showed that cerebral ischemia-reperfusion injury in C3H/Hej mice was less serious than that in C3H/OuJ mice. TNF-{alpha} and IL-6 contents in C3H/HeJ mice were obviously lower than that in C3H/OuJ mice with ELISA. The results showed that TLR4 participates in the process of cerebral ischemia-reperfusion injury probably through decrease of inflammatory cytokines. TLR4 may become a new target for prevention of cerebral ischemia-reperfusion injury. Our study suggests that TLR4 is one of the mechanisms of cerebral ischemia-reperfusion injury besides its important role in innate immunity.

  12. Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research

    PubMed Central

    Gonzalez, Liara M.; Moeser, Adam J.

    2014-01-01

    Research in the field of ischemia-reperfusion injury continues to be plagued by the inability to translate research findings to clinically useful therapies. This may in part relate to the complexity of disease processes that result in intestinal ischemia but may also result from inappropriate research model selection. Research animal models have been integral to the study of ischemia-reperfusion-induced intestinal injury. However, the clinical conditions that compromise intestinal blood flow in clinical patients ranges widely from primary intestinal disease to processes secondary to distant organ failure and generalized systemic disease. Thus models that closely resemble human pathology in clinical conditions as disparate as volvulus, shock, and necrotizing enterocolitis are likely to give the greatest opportunity to understand mechanisms of ischemia that may ultimately translate to patient care. Furthermore, conditions that result in varying levels of ischemia may be further complicated by the reperfusion of blood to tissues that, in some cases, further exacerbates injury. This review assesses animal models of ischemia-reperfusion injury as well as the knowledge that has been derived from each to aid selection of appropriate research models. In addition, a discussion of the future of intestinal ischemia-reperfusion research is provided to place some context on the areas likely to provide the greatest benefit from continued research of ischemia-reperfusion injury. PMID:25414098

  13. Analysis of Spatial and Temporal Protein Expression in the Cerebral Cortex after Ischemia-Reperfusion Injury

    PubMed Central

    Chen, Yuan-Hao; Chiang, Yung-Hsiao

    2014-01-01

    Background and Purpose Hypoxia, or ischemia, is a common cause of neurological deficits in the elderly. This study elucidated the mechanisms underlying ischemia-induced brain injury that results in neurological sequelae. Methods Cerebral ischemia was induced in male Sprague-Dawley rats by transient ligation of the left carotid artery followed by 60 min of hypoxia. A two-dimensional differential proteome analysis was performed using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry to compare changes in protein expression on the lesioned side of the cortex relative to that on the contralateral side at 0, 6, and 24 h after ischemia. Results The expressions of the following five proteins were up-regulated in the ipsilateral cortex at 24 h after ischemia-reperfusion injury compared to the contralateral (i.e., control) side: aconitase 2, neurotensin-related peptide, hypothetical protein XP-212759, 60-kDa heat-shock protein, and aldolase A. The expression of one protein, dynamin-1, was up-regulated only at the 6-h time point. The level of 78-kDa glucose-regulated protein precursor on the lesioned side of the cerebral cortex was found to be high initially, but then down-regulated by 24 h after the induction of ischemia-reperfusion injury. The expressions of several metabolic enzymes and translational factors were also perturbed soon after brain ischemia. Conclusions These findings provide insights into the mechanisms underlying the neurodegenerative events that occur following cerebral ischemia. PMID:24829593

  14. Selective ROCK2 inhibition in focal cerebral ischemia

    PubMed Central

    Hyun Lee, Jeong; Zheng, Yi; von Bornstadt, Daniel; Wei, Ying; Balcioglu, Aygul; Daneshmand, Ali; Yalcin, Nilufer; Yu, Esther; Herisson, Fanny; Atalay, Yahya B; Kim, Maya H; Ahn, Yong-Joo; Balkaya, Mustafa; Sweetnam, Paul; Schueller, Olivier; Poyurovsky, Masha V; Kim, Hyung-Hwan; Lo, Eng H; Furie, Karen L; Ayata, Cenk

    2014-01-01

    Objective Rho-associated kinase (ROCK) is a key regulator of numerous processes in multiple cell types relevant in stroke pathophysiology. ROCK inhibitors have improved outcome in experimental models of acute ischemic or hemorrhagic stroke. However, the relevant ROCK isoform (ROCK1 or ROCK2) in acute stroke is not known. Methods We characterized the pharmacodynamic and pharmacokinetic profile, and tested the efficacy and safety of a novel selective ROCK2 inhibitor KD025 (formerly SLx-2119) in focal cerebral ischemia models in mice. Results KD025 dose-dependently reduced infarct volume after transient middle cerebral artery occlusion. The therapeutic window was at least 3 h from stroke onset, and the efficacy was sustained for at least 4 weeks. KD025 was at least as efficacious in aged, diabetic or female mice, as in normal adult males. Concurrent treatment with atorvastatin was safe, but not additive or synergistic. KD025 was also safe in a permanent ischemia model, albeit with diminished efficacy. As one mechanism of protection, KD025 improved cortical perfusion in a distal middle cerebral artery occlusion model, implicating enhanced collateral flow. Unlike isoform-nonselective ROCK inhibitors, KD025 did not cause significant hypotension, a dose-limiting side effect in acute ischemic stroke. Interpretation Altogether, these data show that KD025 is efficacious and safe in acute focal cerebral ischemia in mice, implicating ROCK2 as the relevant isoform in acute ischemic stroke. Data suggest that selective ROCK2 inhibition has a favorable safety profile to facilitate clinical translation. PMID:24466563

  15. Neuroprotective effect of morroniside on focal cerebral ischemia in rats.

    PubMed

    Wang, Wen; Xu, Jingdong; Li, Lei; Wang, Peichang; Ji, Xunming; Ai, Houxi; Zhang, Li; Li, Lin

    2010-10-30

    Cornus officinalis Sieb. et Zucc., known as Shan-zhu-yu in Chinese, has been used to treat cerebrovascular disease and diabetes in Traditional Chinese Medicine for a long time and morroniside is the main component of Shan-zhu-yu. In this study, we examined whether morroniside could protect ischemia/reperfusion-induced brain injury by minimizing oxidative stress and anti-apoptosis. Morroniside was intragastrically administered to rats in doses of 30, 90 and 270mg/kg/day, starting 3h after the onset of middle cerebral artery occlusion. The behavioral test was performed by using the Zea-Longa scores, Prehensile Traction score and Ludmila Belayer score. Rats were sacrificed 3 days after ischemia occurred. The infarction volume of brain was assessed in the brain slices stained with 2,3,5-triphenyl tetrazolium chloride. Cortex tissues were also used for determination of malondialdehyde levels, glutathione levels and superoxide dismutase. The treatment with morroniside significantly improved Zea-Longa scores and Prehensile Traction score at the doses of 30, 90 and 270mg/kg, increased Ludmila Belayer score and reduced the infarction volume at the doses of 90 and 270mg/kg. Morroniside (30, 90 and 270mg/kg) treatment significantly decreased the level of malondialdehyde and caspase-3 activity by colorimetric analysis in ischemic cortex tissues. Morroniside (270mg/kg) treatment significantly increased the content of glutathione, enhanced the activity of superoxide dismutase, but decreased the caspase-3 expression by Western-blot analysis in ischemic cortex tissues. These findings demonstrated that morroniside could notably protect the brain from damage induced by focal cerebral ischemia which might be related to morroniside antioxidant and anti-apoptotic properties in the brain. PMID:20637265

  16. Guanosine Protects Against Cortical Focal Ischemia. Involvement of Inflammatory Response.

    PubMed

    Hansel, Gisele; Tonon, André Comiran; Guella, Felipe Lhywinskh; Pettenuzzo, Letícia Ferreira; Duarte, Thiago; Duarte, Marta Maria Medeiros Frescura; Oses, Jean Pierre; Achaval, Matilde; Souza, Diogo Onofre

    2015-12-01

    Stroke is the major cause of death and the most frequent cause of disability in the adult population worldwide. Guanosine plays an important neuroprotective role in several cerebral ischemic models and is involved in the modulation of oxidative responses and glutamatergic parameters. Because the excessive reactive oxygen species produced during an ischemic event can trigger an inflammatory response, the purpose of this study was to evaluate the hypothesis that guanosine is neuroprotective against focal cerebral ischemia, inhibits microglia/macrophages activation, and mediates an inflammatory response ameliorating the neural damage. Permanent focal cerebral ischemia was induced in adult rats, and guanosine was administered immediately, 1, 3, and 6 h after surgery. Twenty-four hours after ischemia, the asymmetry scores were evaluated by the cylinder test; neuronal damage was evaluated by Fluoro-Jade C (FJC) staining and propidium iodide (PI) incorporation; microglia and immune cells were evaluated by anti-Iba-1 antibody; and inflammatory parameters such as interleukins (IL): IL-1, IL-6, IL-10; tumor necrosis factors alpha (TNF-α); and interferon-gamma (INF-γ) were evaluated in the brain tissue and cerebrospinal fluid. The ischemic event increased the levels of Iba-1-positive cells and pro-inflammatory cytokines and decreased IL-10 levels (an anti-inflammatory cytokine) in the lesion periphery. The guanosine treatment attenuated the changes in these inflammatory parameters and also reduced the infarct volume, PI incorporation, and number of FJC-positive cells, improving the functional recovery. Thus, guanosine may have been a promising therapeutic agent for the treatment of ischemic brain injury by reduction of inflammatory process triggered in an ischemic event. PMID:25394382

  17. Exercise induces mitochondrial biogenesis after brain ischemia in rats.

    PubMed

    Zhang, Q; Wu, Y; Zhang, P; Sha, H; Jia, J; Hu, Y; Zhu, J

    2012-03-15

    Stroke is a major cause of death worldwide. Previous studies have suggested both exercise and mitochondrial biogenesis contribute to improved post-ischemic recovery of brain function. However, the exact mechanism underlying this effect is unclear. On the other hand, the benefit of exercise-induced mitochondrial biogenesis in brain has been confirmed. In this study, we attempted to determine whether treadmill exercise induces functional improvement through regulation of mitochondrial biogenesis after brain ischemia. We subjected adult male rats to ischemia, followed by either treadmill exercise or non-exercise and analyzed the effect of exercise on the amount of mitochondrial DNA (mtDNA), expression of mitochondrial biogenesis factors, and mitochondrial protein. In the ischemia-exercise group, only peroxisome proliferator activated receptor coactivator-1 (PGC-1) expression was increased significantly after 3 days of treadmill training. However, after 7 days of training, the levels of mtDNA, nuclear respiratory factor 1, NRF-1, mitochondrial transcription factor A, TFAM, and the mitochondrial protein cytochrome C oxidase subunit IV (COXIV) and heat shock protein-60 (HSP60) also increased above levels observed in non-exercised ischemic animals. These changes followed with significant changes in behavioral scores and cerebral infarct volume. The results indicate that exercise can promote mitochondrial biogenesis after ischemic injury, which may serve as a novel component of exercise-induced repair mechanisms of the brain. Understanding the molecular basis for exercise-induced neuroprotection may be beneficial in the development of therapeutic approaches for brain recovery from the ischemic injury. Based upon our findings, stimulation or enhancement of mitochondrial biogenesis may prove a novel neuroprotective strategy in the future. PMID:22266265

  18. Protective metabolic effects of propranolol during total myocardial ischemia.

    PubMed

    Veronee, C D; Lewis, W R; Takla, M W; Hull-Ryde, E A; Lowe, J E

    1986-09-01

    Clinical trials have shown an increase in survival in patients treated with beta blockers after infarction. In addition, the majority of patients undergoing myocardial revascularization are also treated preoperatively with beta blockers. It is commonly thought that beta blockers exert their protective effect primarily by decreasing heart rate and subsequent myocardial work. The present study was designed to determine whether beta blockade has any primary protective metabolic effects on globally ischemic myocardium. Thirty-four anesthetized dogs underwent total myocardial ischemia at 37 degrees C. High-energy nucleotide and lactate levels in left ventricular tissue samples were determined at control and at 15 minute intervals as well as at the onset of ischemic contracture in 24 dogs. Seventeen dogs were treated with propranolol before ischemia. The time to ischemic contracture in control dogs was 63.3 +/- 1.4 minutes compared with 75.9 +/- 2.2 minutes in the propranolol-treated group (p less than 0.01). In addition to significantly delaying the onset of ischemic contracture, propranolol also decreased the rate of anaerobic glycolysis during ischemia. Ischemic contracture occurred in the control group with an average adenosine triphosphate level of 1.26 +/- 0.08 mumol compared to 0.91 +/- 0.08 mumol/gm wet weight for the beta blocked group (p less than 0.0025). These are the first data suggesting that the protective effects of beta blockade may be related to a beneficial effect on ischemic myocardial metabolism allowing myocardium to survive with lower levels of adenosine triphosphate. PMID:3018382

  19. Antithrombin is protective against myocardial ischemia and reperfusion injury

    PubMed Central

    Wang, Jingying; Wang, Yanqing; Wang, Jinli; Gao, Junjie; Tong, Chao; Manithody, Chandrashekhara; Li, Ji; Rezaie, Alireza R.

    2013-01-01

    Summary Background Antithrombin (AT) is a plasma serpin inhibitor that regulates the proteolytic activity of procoagulant proteases of the clotting cascade. In addition to its anticoagulant activity, AT also possesses potent antiinflammatory properties. Objectives The objective of this study is to investigate the antiinflammatory activity of wild-type AT (AT-WT) and a reactive center loop mutant of AT (AT-RCL) which is not capable of inhibiting thrombin. Methods Cardioprotective activities of AT-WT and AT-RCL were monitored in a mouse model of ischemia/reperfusion injury in which the left anterior descending coronary artery was occluded and then released. Results We demonstrate that AT markedly reduces myocardial infarct size by a mechanism that is independent of its anticoagulant activity. Thus, AT-RCL attenuated myocardial infarct size to the same extent as AT-WT in this acute injury model. Further studies revealed that AT binds to vascular heparan sulfate proteoglycans via its heparin-binding domain to exert its protective activity as evidenced by the therapeutic AT-binding pentasaccharide (fondaparinux) abrogating the cardioprotective activity of AT and a heparin-site mutant of AT exhibiting no cardioprotective property. We further demonstrate that AT up-regulates production of prostacyclin in myocardial tissues and inhibits expression of proinflammatory cytokines TNF-α and IL-6 in vivo by attenuating ischemia/reperfusion-induced JNK and NF-κB signaling pathways. Conclusions Our results suggest that both AT and the non-anticoagulant AT-RCL, through their antiinflammatory signaling effects, elicit potent cardioprotective responses. Thus, AT may have therapeutic potential for treating cardiac ischemia/reperfusion injury. PMID:23582062

  20. Phosphorylation and Assembly of Glutamate Receptors after Brain Ischemia

    PubMed Central

    Zhang, Fan; Guo, Ailan; Liu, Chunli; Comb, Micheal; Hu, Bingren

    2012-01-01

    Background and Purpose Over-assembly of synaptic glutamate receptors leads to excitotoxicity. The goal of this study is to investigate phosphorylation and assembly of AMPA and NMDA receptors after brain ischemia with reperfusion (I/R). Methods Rats were subjected to 15 min of global ischemia followed by 0.5, 4, and 24 h of reperfusion. Phosphotyrosine (Ptyr) peptides of glutamate receptors in synaptosomal fraction after I/R were identified and quantified by state-of-the-art immuno-affinity purification of Ptyr peptides followed by LC-MS/MS analysis (IAP-LC/MS/MS). Glutamate receptor phosphorylation and synaptic assembly after I/R were studied by biochemical methods. Results Numerous Ptyr sites of AMPA and NMDA were upregulated by about 2- to 37-fold after I/R. A core glutamate receptor kinase, Src kinase, was significantly activated. GluR2/3 and NR2A/B were rapidly clustered from extrasynaptic to synaptic membrane fractions after I/R. GluR2/3 was then translocated into the intracellular pool, whereas NR2A/B remained in the synaptic fraction for as long as 24 h. Consistently, trafficking-related phosphorylation of GluR2/3-S880 was significantly but transiently upregulated, whereas NR2A/B-Y1246 and -Y1472 were significantly and persistently upregulated after I/R. Conclusions Phosphorylation of glutamate receptors at synapses may lead to over-assembly of glutamate receptors, probably via activation of Src family kinases, after I/R. This study provides “global” proteomic information about glutamate receptor tyrosine phosphorylation after brain ischemia. PMID:23212166

  1. Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective opportunities.

    PubMed

    Nakka, Venkata Prasuja; Gusain, Anchal; Mehta, Suresh L; Raghubir, Ram

    2008-02-01

    Cerebral ischemia/reperfusion (I/R) injury triggers multiple and distinct but overlapping cell signaling pathways, which may lead to cell survival or cell damage. There is overwhelming evidence to suggest that besides necrosis, apoptosis do contributes significantly to the cell death subsequent to I/R injury. Both extrinsic and intrinsic apoptotic pathways play a vital role, and upon initiation, these pathways recruit downstream apoptotic molecules to execute cell death. Caspases and Bcl-2 family members appear to be crucial in regulating multiple apoptotic cell death pathways initiated during I/R. Similarly, inhibitor of apoptosis family of proteins (IAPs), mitogen-activated protein kinases, and newly identified apoptogenic molecules, like second mitochondrial-activated factor/direct IAP-binding protein with low pI (Smac/Diablo), omi/high-temperature requirement serine protease A2 (Omi/HtrA2), X-linked mammalian inhibitor of apoptosis protein-associated factor 1, and apoptosis-inducing factor, have emerged as potent regulators of cellular apoptotic/antiapoptotic machinery. All instances of cell survival/death mechanisms triggered during I/R are multifaceted and interlinked, which ultimately decide the fate of brain cells. Moreover, apoptotic cross-talk between major subcellular organelles suggests that therapeutic strategies should be optimally directed at multiple targets/mechanisms for better therapeutic outcome. Based on the current knowledge, this review briefly focuses I/R injury-induced multiple mechanisms of apoptosis, involving key apoptotic regulators and their emerging roles in orchestrating cell death programme. In addition, we have also highlighted the role of autophagy in modulating cell survival/death during cerebral ischemia. Furthermore, an attempt has been made to provide an encouraging outlook on emerging therapeutic approaches for cerebral ischemia. PMID:18066503

  2. Meclizine Preconditioning Protects the Kidney Against Ischemia-Reperfusion Injury.

    PubMed

    Kishi, Seiji; Campanholle, Gabriela; Gohil, Vishal M; Perocchi, Fabiana; Brooks, Craig R; Morizane, Ryuji; Sabbisetti, Venkata; Ichimura, Takaharu; Mootha, Vamsi K; Bonventre, Joseph V

    2015-09-01

    Global or local ischemia contributes to the pathogenesis of acute kidney injury (AKI). Currently there are no specific therapies to prevent AKI. Potentiation of glycolytic metabolism and attenuation of mitochondrial respiration may decrease cell injury and reduce reactive oxygen species generation from the mitochondria. Meclizine, an over-the-counter anti-nausea and -dizziness drug, was identified in a 'nutrient-sensitized' chemical screen. Pretreatment with 100 mg/kg of meclizine, 17 h prior to ischemia protected mice from IRI. Serum creatinine levels at 24 h after IRI were 0.13 ± 0.06 mg/dl (sham, n = 3), 1.59 ± 0.10 mg/dl (vehicle, n = 8) and 0.89 ± 0.11 mg/dl (meclizine, n = 8). Kidney injury was significantly decreased in meclizine treated mice compared with vehicle group (p < 0.001). Protection was also seen when meclizine was administered 24 h prior to ischemia. Meclizine reduced inflammation, mitochondrial oxygen consumption, oxidative stress, mitochondrial fragmentation, and tubular injury. Meclizine preconditioned kidney tubular epithelial cells, exposed to blockade of glycolytic and oxidative metabolism with 2-deoxyglucose and NaCN, had reduced LDH and cytochrome c release. Meclizine upregulated glycolysis in glucose-containing media and reduced cellular ATP levels in galactose-containing media. Meclizine inhibited the Kennedy pathway and caused rapid accumulation of phosphoethanolamine. Phosphoethanolamine recapitulated meclizine-induced protection both in vitro and in vivo. PMID:26501107

  3. Effect of hydrogen sulfide on inflammatory cytokines in acute myocardial ischemia injury in rats

    PubMed Central

    LIU, FANG; LIU, GUANG-JIE; LIU, NA; ZHANG, GANG; ZHANG, JIAN-XIN; LI, LAN-FANG

    2015-01-01

    Hydrogen sulfide (H2S) is believed to be involved in numerous physiological and pathophysiological processes, and now it is recognized as the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide; however, the effects of H2S on inflammatory factors in acute myocardial ischemia injury in rats have not been clarified. In the present study, sodium hydrosulfide (NaHS) was used as the H2S donor. Thirty-six male Sprague Dawley rats were randomly divided into five groups: Sham, ischemia, ischemia + low-dose (0.78 mg/kg) NaHS, ischemia + medium-dose (1.56 mg/kg) NaHS, ischemia + high-dose (3.12 mg/kg) NaHS and ischemia + propargylglycine (PPG) (30 mg/kg). The rats in each group were sacrificed 6 h after the surgery for sample collection. Compared with the ischemia group, the cardiac damage in the rats in the ischemia + NaHS groups was significantly reduced, particularly in the high-dose group; in the ischemia + PPG group, the myocardial injury was aggravated compared with that in the ischemia group. Compared with the ischemia group, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the serum of rats in the ischemia + medium- and high-dose NaHS groups were significantly reduced, and the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein in the myocardial tissues of rats was significantly reduced. In the ischemia + PPG group, the TNF-α, IL-1β and IL-6 levels in the serum were significantly increased, the expression of ICAM-1 mRNA was increased, although without a significant difference, and the expression of NF-κB was increased. The findings of the present study provide novel evidence for the dual effects of H2S on acute myocardial ischemia injury via the modulation of inflammatory factors. PMID:25667680

  4. Modulation of Cardiac Potassium Current by Neural Tone and Ischemia.

    PubMed

    Tomson, Todd T; Arora, Rishi

    2016-06-01

    The cardiac action potential is generated by intricate flows of ions across myocyte cell membranes in a coordinated fashion to control myocardial contraction and the heart rhythm. Modulation of the flow of these ions in response to a variety of stimuli results in changes to the action potential. Abnormal or altered ion currents can result in cardiac arrhythmias. Abnormalities of autonomic regulation of potassium current play a role in the genesis of cardiac arrhythmias, and alterations in acetylcholine-activated potassium channels may play a key role in atrial fibrillation. Ischemia is another important modulator of cardiac cellular electrophysiology. PMID:27261826

  5. [Intra-arterial fibrinolytic therapy for acute mesenteric ischemia].

    PubMed

    Michel, C; Laffy, P; Leblanc, G; Riou, J Y; Chaloum, S; Maklouf, M; Le Guen, O; Pitre, J

    2001-01-01

    We report a case of mesenteric ischemia secondary to embolic occlusion treated by percutaneous intra-arterial thrombolysis. Early initial radiographic evaluation included abdominal plain film, ultrasonography, abdominal CT, and arteriography. Only selective superior mesenteric artery angiography provided definite diagnosis. The duration of ischemic symptoms before thrombolysis was 6 hours. Post procedure angiogram at 12 hours showed complete resolution of the mesenteric arterial thrombus with clinical improvement. The most important criteria for patient survival is early diagnosis and immediate treatment. Direct infusion of urokinase into the superior mesentric artery may be an alternative to surgery in selected patients and particularly in patients without evidence of frank bowel necrosis. PMID:11223630

  6. In vivo study of myocardial elastography under graded ischemia conditions

    NASA Astrophysics Data System (ADS)

    Lee, Wei-Ning; Provost, Jean; Fujikura, Kana; Wang, Jie; Konofagou, Elisa E.

    2011-02-01

    The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction

  7. Penile Replantation After Five Hours of Warm Ischemia.

    PubMed

    Facio, Fernando N; Spessoto, Luis C; Arruda, Pedro; Paiva, Cristiano S; Arruda, José G; Facio, Maria F

    2015-05-01

    Although a rare occurrence, this event may occur as a result of self-mutilation among individuals with psychiatric disturbances or due to work-related accidents, iatrogenic injuries or the actions of individuals motivated by jealously, rage and feelings of betrayal. In western societies, most penile amputations are the result of self-aggression during a psychotic episode, the treatment of victims involves resuscitation, stabilization and immediate psychiatric support. The amputated tissue must be preserved under hypothermic conditions. Micro-surgery is currently the most widely employed method for penile replantation. This paper describes a successful case of penile replantation following 5 hours of warm ischemia. PMID:26793508

  8. A Strange Case of Left Bowel Ischemia after Right Hernioplasty

    PubMed Central

    Geraci, Girolamo; Pisello, Franco; Modica, Giuseppe; Li Volsi, Francesco; Cajozzo, Massimo; Sciumè, Carmelo

    2010-01-01

    We report the first observed case of a young man who suffered of large and unsuspected left bowel ischemia following an elective right open hernioplasty. A 54-year-old man had a 2-year history of right inguinal reducible mass and was admitted to hospital for an elective day case open inguinal hernioplasty for a direct right inguinal hernia. Apart from mild hypertension controlled with ACE inhibitor, he was medically fit and well. The patient was submitted to open tension-free mesh repair with polypropylene preshaped mesh with local infiltration anesthesia and additive sedation with midazolam. The local anesthesia and surgery were uneventful and he was discharged home on the same day as per day case protocol. He was readmitted about 12 h after discharge with a history of central and left lower abdominal pain with palpable mass, and distension and fever (38°C). After imaging and laboratory studies the patient was submitted to explorative surgery with the suspicion of left colonic ischemia. After intraoperative confirmation we performed standard left hemicolectomy. The postoperative course was uneventful; the patient was discharged in good general condition on the 7th postoperative day. Actually, the patient is in follow-up, with normal coagulation and hemochromocytometric pattern, asymptomatic for hypercholesterolemia and atrial flutter/fibrillation. Complications relating to bowel during open techniques of hernia repair are limited to two situations: the freeing of an incarcerated or strangulated segment of bowel and inadvertent laceration of large bowel in the presence of a sliding hernia. Following this strange case of colonic ischemia, a boolean Medline search (terms: hernia, complication, repair, groin, herniorrhaphy, hernioplasty, all major MESH subjects without language restriction) revealed no previous similar cases reported. However, to our knowledge, there is another trouble hypothesis: not causality but casualty. In conclusion, to our knowledge this is

  9. Spinal cord ischemia resulting in paraplegia following extrapleural pneumonectomy.

    PubMed

    Ural, Kelly; Jakob, Kyle; Lato, Scott; Gilly, George; Landreneau, Rodney

    2014-08-01

    A patient undergoing radical extrapleural pneumonectomy for epithelioid malignant mesothelioma developed acute paraplegia postoperatively related to long-segment spinal cord ischemia. The usual area of concern for this complication is the T9 to T12 area where the artery of Adamkiewicz is most likely to originate. In this patient, there was ligation of only upper thoracic, ipsilateral segmental arteries from the T3 to T6 level, yet he still developed paraplegia. Our hypothesis is variant mid-thoracic vascular anatomy. Previously unreported, to our knowledge, this should be understood as a rare complication of this surgery. PMID:25091760

  10. Platelet activating factor receptor blockade enhances recovery after multifocal brain ischemia

    SciTech Connect

    Kochanek, P.M.; Dutka, A.J.; Kumaroo, K.K.; Hallenbech, J.M.

    1987-12-14

    The authors treated four anesthetized dogs with the platelet activating factor (PAF) receptor antagonist kadsurenone prior to 60 min of multifocal ischemia induced by air embolism, and measured neuronal recovery, blood flow and autologous /sup 111/In-labeled platelet accumulation for 4 h after ischemia. Four anesthetized animals with identical ischemia served as controls. Kadsurenone administered 5 min prior to ischemia and continuously throughout ischemia and recovery significantly enhanced recovery of cortical somatosensory evoked response (CSER) amplitude when compared to controls. They estimated platelet accumulation as /sup 111/In activity (cmp/g tissue) in the injured hemisphere minus that in the non-injured hemisphere. Kadsurenone treated animals did not exhibit significantly altered /sup 111/In labeled platelet accumulation when compared to controls. Beneficial effects of PAF receptor blockade other than those on platelet accumulation may be involved. 20 references, 1 figure.

  11. Effect of Fluoxetine on Neurogenesis in Hippocampal Dentate Gyrus after Global Transient Cerebral Ischemia in Rats.

    PubMed

    Khodanovich, M Yu; Kisel', A A; Chernysheva, G A; Smol'yakova, V I; Savchenko, R R; Plotnikov, M B

    2016-07-01

    Changes in cerebral neurogenesis provoked by ischemia and the effect of fluoxetine on this process were studied using a three-vessel occlusion model of global transient cerebral ischemia. The global transient cerebral ischemia was modeled on male Wistar rats by transient occlusion of three major vessels originating from the aortic arch and supplying the brain (brachiocephalic trunk, left subclavian artery, and left common carotid artery). The cells expressing doublecortin (DCX, a marker of young neurons) were counted in the hippocampal dentate gyrus on day 31 after ischemia modeling. It was found that ischemia inhibited neurogenesis in the dentate gyrus in comparison with sham-operated controls (p<0.05), while fluoxetine (20 mg/kg/day) injected over 10 days after surgery restored neurogenesis to the control level (p<0.001). PMID:27496030

  12. In vivo determination of acute myocardial ischemia based on photoacoustic imaging with a focused transducer

    NASA Astrophysics Data System (ADS)

    Li, Zhifang; Li, Hui; Chen, Haiyu; Xie, Wengming

    2011-07-01

    The location and ischemia extent are two important parameters for evaluating the acute myocardial ischemia (AMI). A focused-transducer-based photoacoustic imaging method was employed to assess time-dependent AMI. Our preliminary results show that the photoacoustic signal could identify the myocardium. The intensity and area of photoacoustic images of myocardium could be used for characterizing the ischemia extent and scope of myocardial ischemia. The results also imply that the intensity and area of photoacoustic images are the rapid fall of an exponential model with an increase of delaying time after the left anterior descending coronary artery (LAD) occlusion. These experimental results were consistent with the clinical characteristics. The findings suggest that the photoacoustic imaging be a potential tool for the real-time assessment of acute myocardial ischemia during surgical operation.

  13. Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death.

    PubMed

    Sanchez, Gina; Berrios, Daniela; Olmedo, Ivonne; Pezoa, Javier; Riquelme, Jaime A; Montecinos, Luis; Pedrozo, Zully; Donoso, Paulina

    2016-01-01

    Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination. There is scarce information on the activity of the 20S proteasome during cardiac ischemia. Accordingly, the aim of this work was to determine the effects of 30 minutes of ischemia, or 30 min of ischemia followed by 60 minutes of reperfusion on the three main peptidase activities of the 20S proteasome in Langendorff perfused rat hearts. We found that 30 min of ischemia produced a significant increase in the chymotrypsin-like activity of the proteasome, without changes in its caspase-like or trypsin-like activities. In contrast, all three activities were decreased upon reperfusion. Ixazomib, perfused before ischemia at a concentration that reduced the chymotrypsin-like activity to 50% of the control values, without affecting the other proteasomal activities, improved the hemodynamic parameters upon reperfusion and decreased the infarct size. Ixazomib also prevented the 50% reduction in RyR2 content observed after ischemia. The protection was lost, however, when simultaneous inhibition of chymotrypsin-like and caspase-like activities of the proteasome was achieved at higher concentration of ixazomib. Our results suggest that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion. PMID:27529620

  14. Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death

    PubMed Central

    Sanchez, Gina; Berrios, Daniela; Olmedo, Ivonne; Pezoa, Javier; Riquelme, Jaime A.; Montecinos, Luis; Pedrozo, Zully; Donoso, Paulina

    2016-01-01

    Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination. There is scarce information on the activity of the 20S proteasome during cardiac ischemia. Accordingly, the aim of this work was to determine the effects of 30 minutes of ischemia, or 30 min of ischemia followed by 60 minutes of reperfusion on the three main peptidase activities of the 20S proteasome in Langendorff perfused rat hearts. We found that 30 min of ischemia produced a significant increase in the chymotrypsin-like activity of the proteasome, without changes in its caspase-like or trypsin-like activities. In contrast, all three activities were decreased upon reperfusion. Ixazomib, perfused before ischemia at a concentration that reduced the chymotrypsin-like activity to 50% of the control values, without affecting the other proteasomal activities, improved the hemodynamic parameters upon reperfusion and decreased the infarct size. Ixazomib also prevented the 50% reduction in RyR2 content observed after ischemia. The protection was lost, however, when simultaneous inhibition of chymotrypsin-like and caspase-like activities of the proteasome was achieved at higher concentration of ixazomib. Our results suggest that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion. PMID:27529620

  15. Inhibition of Glycogen Synthase Kinase-3β Improves Tolerance to Ischemia in Hypertrophied Hearts

    PubMed Central

    Barillas, Rodrigo; Friehs, Ingeborg; Cao-Danh, Hung; Martinez, Joseph F.; del Nido, Pedro J.

    2012-01-01

    Background Hypertrophied myocardium is more susceptible to ischemia/reperfusion injury, in part owing to impaired insulin-mediated glucose uptake. Glycogen synthase kinase-3β (GSK-3β) is a key regulatory enzyme in glucose metabolism that, when activated, phosphorylates/inactivates target enzymes of the insulin signaling pathway. Glycogen synthase kinase-3β is regulated upstream by Akt-1. We sought to determine whether GSK-3β is activated in ischemic hypertrophied myocardium owing to impaired Akt-1 function, and whether inhibition with lithium (Li) or indirubin-3′-monoxime,5-iodo- (IMI), a specific inhibitor, improves post-ischemic myocardial recovery by improving glucose metabolism. Methods Pressure-overload hypertrophy was achieved by aortic banding in neonatal rabbits. At 6 weeks, isolated hypertrophied hearts underwent 30 minutes of normothermic ischemia and reperfusion with or without GSK-3β inhibitor (0.1 mM Li; 1 µM IMI) as cardioplegic additives. Cardiac function was measured before and after ischemia. Expression, activity of Akt-1 and GSK-3β, and lactate were determined at end-ischemia. Results Contractile function after ischemia was better preserved in hypertrophied hearts treated with GSK-3β inhibitors. Activity of Akt-1 was significantly impaired in hypertrophied myocardium at end-ischemia. Glycogen synthase kinase-3β enzymatic activity at end-ischemia was increased in hypertrophied hearts and was blocked by Li or IMI concomitant with significantly increased lactate production, indicating increased glycolysis. Conclusions Regulatory inhibition of GSK-3β by Akt-1 in hypertrophied hearts is impaired, leading to activation during ischemia. Inhibition of GSK-3β by Li or IMI improves tolerance to ischemia/reperfusion injury in hypertrophied myocardium. The likely protective mechanism is an increase in insulin-mediated glucose uptake, resulting in greater substrate availability for glycolysis during ischemia and early reperfusion. PMID:17588398

  16. Progressive changes in detrusor function and micturition patterns with chroinc bladder ischemia

    PubMed Central

    Zhao, Zuohui; Azad, Roya; Yang, Jing-Hua; Siroky, Mike B.

    2016-01-01

    Purpose Lower urinary tract symptoms (LUTS) are bothersome constellation of voiding symptoms in men and women as they age. Multiple factors and comorbidities are attributed to this problem but underlying mechanisms of nonobstructive nonneurogenic detrusor overactivity, detrusor underactivity and LUTS remain largely unknown. Our goal was to characterize detrusor function and voiding patterns in relation to muscarinic receptors expression, nerve fiber density, and neural ultrastructure in chronic bladder ischemia. Materials and Methods Iliac artery atherosclerosis and bladder ischemia were produced in male Sprague-Dawley rats. At 8 and 16 weeks after ischemia, micturition patterns and cystometrograms were recorded in conscious rats then bladder blood flow and nonvoiding spontaneous contractions were measured under general anesthesia. Bladder tissues were processed for Western blotting, immunostaining, and transmission electron microscopy. Results Bladder responses to ischemic insult depended on the duration of ischemia. Micturition patterns and cystometric changes at 8-week ischemia suggested detrusor overactivity, while voiding behavior and cystometrograms at 16-week ischemia implied abnormal detrusor function resembling underactivity. Upregulation of muscarinic M2 receptor was found after 8- and 16 weeks of ischemia. Downregulation of M3 and upregulation of M1 were detected at 16-week ischemia. Neural structural damage and marked neurodegeneration were found after 8 and 16 weeks of ischemia, respectively. Conclusions Prolonged ischemia may be a mediating variable in progression of overactive bladder to dysfunctional patterns similar to detrusor underactivity. The mechanism appears to involve differential expression of M1, M2, and M3 receptors, neural structural injury, and progressive loss of nerve fibers. PMID:27437534

  17. Ischemia-Induced Changes of PRAS40 and p-PRAS40 Immunoreactivities in the Gerbil Hippocampal CA1 Region After Transient Cerebral Ischemia.

    PubMed

    Park, Joon Ha; Shin, Bich Na; Ahn, Ji Hyeon; Cho, Jeong-Hwi; Kim, In Hye; Kim, Dae Won; Won, Moo-Ho; Hong, Seongkweon; Cho, Jun Hwi; Lee, Choong-Hyun

    2016-07-01

    Proline-rich Akt substrate of 40-kDa (PRAS40) is one of the important interactive linkers between Akt and mTOR signaling pathways. The increase of PRAS40 is related with the reduction of brain damage induced by cerebral ischemia. In the present study, we investigated time-dependent changes in PRAS40 and phospho-PRAS40 (p-PRAS40) immunoreactivities in the hippocampal CA1 region of the gerbil after 5 min of transient cerebral ischemia. PRAS40 immunoreactivity in the CA1 region was decreased in pyramidal neurons from 12 h after ischemic insult in a time-dependent manner, and, at 5 days post-ischemia, PRAS40 immunoreactivity was newly expressed in astrocytes. p-PRAS40 immunoreactivity in the CA1 pyramidal neurons was hardly found 12 h and apparently detected again 1 and 2 days after ischemic insult. At 5 days post-ischemia, p-PRAS40 immunoreactivity in the CA1 pyramidal neurons was not found. These results indicate that ischemia-induced changes in PRAS40 and p-PRAS40 immunoreactivities in CA1 pyramidal neurons and astrocytes may be closely associated with delayed neuronal death in the hippocampal CA1 region following transient cerebral ischemia. PMID:26526334

  18. Defining the Collateral Flow of Posterior Tibial Artery and Dorsalis Pedis Artery in Ischemic Foot Disease: Is It a Preventing Factor for Ischemia?

    PubMed Central

    Tutar, Onur; Yildirim, Duzgun; Samanci, Cesur; Rafiee, Babak; Inan, Kaan; Dikici, Suleyman; Ustabasioglu, Fethi Emre; Kuyumcu, Gokhan

    2016-01-01

    Background: Critical limb ischemia, a worldwide prevalent morbidity cause, is mostly secondary to vascular insufficiency due to atherosclerosis. The disease presents with intermittent claudication, which can progress to critical limb ischemia requiring amputation. Research has emphasized that the quality or existence of the pedal arch have a direct effect on wound healing and, therefore, on limb salvage, through the mechanism of collateral vascularization to the ischemic regions. Objectives: This study aimed to determine the existence and, if present, grade of retrograde blood flow from plantar arch to dorsal foot artery (dorsalis pedis artery, DPA). The correlation between clinical symptoms and presence of collateral flow were also investigated. Patients and Methods: Study group consisted of 34 cases, which included patient group (n = 17, all male, mean age: 68 years) and control group (n = 17, all male, mean age: 66 years). After physical examination and lower extremity Doppler examination, spectral morphology of DPA flow was recorded, before and during manual compression of posterior tibial artery (PTA), for a period of 5 seconds. At the end, findings of Doppler ultrasound, computed tomography angiography, magnetic resonance angiography and, physical examination finding and symptomatology were gathered and analyzed. Results: In the patient group, 31 lower limb arteries, of total of 17 cases, were included. After compression maneuver, DPA in 11 cases (six right, five left) showed retrograde filling from plantar arch. This retrograde flow support was triphasic in three cases, biphasic in five cases, and monophasic in three cases. In other DPAs of these 20 limbs, PTA based retrograde collateral flow was not determined. In nine of these 20 limbs, with no or diminished retrograde filling, symptoms were worse than in other cases. Contrarily, only two of 11 limbs, with retrograde collaterals, have claudication during walking. Conclusion: In cases with critical

  19. Lactation protects against myocardial ischemia-reperfusion injury in rats.

    PubMed

    Shekarforoush, S; Safari, F

    2015-12-01

    Some researchers have reported that lactation is effective in reducing cardiovascular disease risk factors. The purpose of this study was to investigate whether lactation may improve intrinsic tolerance against ischemia reperfusion (IR) injury. The rats were randomly divided into two groups (n = 8 in each group). In the lactation (Lact) group, the surgery was performed on postpartum day 21 (at the end of lactation period) and the results were compared with those of virgin female rats (control group). Cardiac IR injury was induced by means of left anterior descending coronary artery occlusion for 30 min followed by reperfusion for 120 min. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. At the end of the experiment, Mean arterial pressure in the control group was significantly lower than that in the Lact group. Myocardial infarct size was significantly reduced in the Lact group (23 ± 3% vs. 45 ± 8%, p < 0.05 in the control group). Lactation reduced the extent of myocardial injury induced by ischemia and reperfusion. So, lactation may increase cardiac tolerance to ischemic injury. PMID:26690029

  20. Cardiac cell survival and reversibility of myocardial ischemia.

    PubMed

    Rashed, E; Depre, C

    2006-12-01

    Because of a limited capacity for cell regeneration, the cardiac tissue, when submitted to ischemic stress, may activate endogenous mechanisms of cell survival resulting in physiological conditions of adaptation to ischemia, known as myocardial stunning, ischemic preconditioning and myocardial hibernation. These conditions result from a switch in gene and protein expression, which sustains cardiac cell survival in a context of oxygen deprivation and during the stress of reperfusion. Understanding how the molecular adaptation of the cardiac myocyte during stress sustains its survival in these conditions might help to define novel mechanisms of endogenous myocardial salvage, in order to expand the conditions of maintained cellular viability and functional salvage of the ischemic myocardium. This review summarizes recent progress made in the study of the molecular pathways controlling reversible ischemic dysfunction, and the unraveling of novel genomic paradigms. We also focus on the discovery and characterization of novel genes, which further increase our knowledge of myocardial ischemia and open novel therapeutic possibilities for ischemic heart disease. PMID:18942527

  1. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    SciTech Connect

    Khodanovich, M. Yu.

    2015-11-17

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  2. Protective Effects of HDL Against Ischemia/Reperfusion Injury

    PubMed Central

    Gomaraschi, Monica; Calabresi, Laura; Franceschini, Guido

    2016-01-01

    Several lines of evidence suggest that, besides being a strong independent predictor of the occurrence of primary coronary events, a low plasma high density lipoprotein (HDL) cholesterol level is also associated with short- and long-term unfavorable prognosis in patients, who have recovered from a myocardial infarction, suggesting a direct detrimental effect of low HDL on post-ischemic myocardial function. Experiments performed in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury have clearly shown that HDL are able to preserve cardiac function when given before ischemia or at reperfusion; the protective effects of HDL against I/R injury have been also confirmed in other tissues and organs, as brain and hind limb. HDL were shown to act on coronary endothelial cells, by limiting the increase of endothelium permeability and promoting vasodilation and neoangiogenesis, on white blood cells, by reducing their infiltration into the ischemic tissue and the release of pro-inflammatory and matrix-degrading molecules, and on cardiomyocytes, by preventing the activation of the apoptotic cascade. Synthetic HDL retains the cardioprotective activity of plasma-derived HDL and may become a useful adjunctive therapy to improve clinical outcomes in patients with acute coronary syndromes or undergoing coronary procedures. PMID:26834639

  3. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    NASA Astrophysics Data System (ADS)

    Khodanovich, M. Yu.

    2015-11-01

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  4. Thallium-201 myocardial scintigraphy in acute myocardial infarction and ischemia

    SciTech Connect

    Wackers, F.J.

    1982-04-01

    Thallium-201 scintigraphy provides a sensitive and reliable method of detecting acute myocardial infarction and ischemia when imaging is performed with understanding of the temporal characteristics and accuracy of the technique. The results of scintigraphy are related to the time interval between onset of symptoms and time of imaging. During the first 6 hr after chest pain almost all patients with acute myocardial infarction and approximately 50% of the patients with unstable angina will demonstrate /sup 201/TI pefusion defects. Delayed imaging at 2-4 hr will permit distinction between ischemia and infarction. In patients with acute myocardial infarction, the size of the perfusion defect accurately reflects the extent of the infarcted and/or jeopardized myocardium, which may be used for prognostic stratification. In view of the characteristics of /sup 201/TI scintigraphy, the most practical application of this technique is in patients in whom myocardial infarction has to be ruled out, and for early recognition of patients at high risk for complications.

  5. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

    NASA Astrophysics Data System (ADS)

    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  6. Adult midgut malrotation presented with acute bowel obstruction and ischemia

    PubMed Central

    Zengin, Akile; Uçar, Bercis İmge; Düzgün, Şükrü Aydın; Bayhan, Zülfü; Zeren, Sezgin; Yaylak, Faik; Şanal, Bekir; Bayhan, Nilüfer Araz

    2016-01-01

    Introduction Intestinal malrotation refers to the partial or complete failure of rotation of midgut around the superior mesenteric vessels in embryonic life. Arrested midgut rotation results due to narrow-based mesentery and increases the risk of twisting midgut and subsequent obstruction and necrosis. Presentation of case 40 years old female patient admitted to emergency service with acute abdomen and computerized tomography scan showed dilated large and small intestine segments with air-fluid levels and twisted mesentery around superior mesenteric artery and vein indicating “whirpool sign”. Discussion Malrotation in adults is a rare cause of midgut volvulus as though it should be considered in differential diagnosis in patients presented with acute abdomen and intestinal ischemia. Even though clinical symptoms are obscure, adult patients usually present with vomiting and recurrent abdominal pain due to chronic partial obstruction. Contrast enhanced radiograph has been shown to be the most accurate method. Typical radiological signs are corkscrew sign, which is caused by the dilatation of various duodenal segments at different levels and the relocation of duodenojejunal junction due to jejunum folding. As malrotation commonly causes intestinal obstruction, patients deserve an elective laparotomy. Conclusion Malrotation should be considered in differential diagnosis in patients presented with acute abdomen and intestinal ischemia. Surgical intervention should be prompt to limit morbidity and mortality. PMID:27015011

  7. Cold ischemia-induced autophagy in rat lung tissue

    PubMed Central

    CHEN, XU; WU, JING-XIANG; YOU, XING-JI; ZHU, HONG-WEI; WEI, JIONG-LIN; XU, MEI-YING

    2015-01-01

    Autophagy is a highly conserved pathway that permits recycling of nutrients within the cell and is rapidly upregulated during starvation or cell stress. Autophagy has been implicated in the pathophysiological process of warm ischemia-reperfusion injury in the rat lung. Cold ischemia (CI) preservation for lung transplantation also exhibits cell stress and nutrient deprivation, however, little is known with regard to the involvement of autophagy in this process. In the present study, CI preservation-induced autophagy and apoptosis was investigated in the lungs of Sprague Dawley rats. Sprague Dawley rat lungs were flushed and preserved at 4°C (i.e. CI) for various durations (0, 3, 6, 12 and 24 h). The levels of autophagy, autophagic cell death and apoptosis were measured at each time point following CI. The results revealed that autophagy was induced by CI preservation, which was initiated at 3 h, peaked at 6 h after CI and declined thereafter. Additionally, a coexistence of autophagic cell death and apoptosis was observed in rat lung tissues following prolonged CI. These findings demonstrate that autophagy is involved in the pathophysiological process of lung CI. Furthermore, autophagic cell death in addition to necrosis and apoptosis occurs following CI in the lung. CI preservation may therefore be a potential mechanism of lung injury during organ preservation prior to lung transplantation. PMID:25435100

  8. Sickle cell anemia: does myocardial ischemia occur during crisis?

    PubMed Central

    Norris, S.; Johnson, C. S.; Haywood, L. J.

    1991-01-01

    The possibility that myocardial ischemia may be associated with chest pain during painful crises was evaluated prospectively in 20 patients (11 women and nine men) with sickle cell disease (19 SS, 1 S beta + thalassemia). Sixteen of 20 (80%) had abnormal ECGs, 7 (35%) had transient ST-T wave changes, and 3 (15%) had persistent ST-T wave changes, both consistent with ischemia; 6 (30%) had nonspecific ST-T changes, and 4 (20%) had normal tracings. Serum enzymes (CK, SGOT, LDH) were abnormal in 16 of 19 (84%); 1 had CK-MB detected, (5%) and 1 had LDH1 to LDH2 reversal. All 10 Tc-99m pyrophosphate scans performed were negative; 4 of 6 (66%) thallium-201 scans had focal defects, and 5 of 8 (63%) radionuclide angiograms (MUGAs) had focal wall motion abnormalities. Three of 8 (38%) MUGAs showed cardiac dilation, diffuse hypokinesis, and reduced ejection fractions. Thus, myocardial damage may be a potentially serious complication of patients with sickle cell anemia who present with chest pain during painful crises. Studies are indicated to define the significance and pathophysiology of these observations. PMID:2038080

  9. Tissue factor and thrombin mediate myocardial ischemia-reperfusion injury.

    PubMed

    Chong, Albert J; Pohlman, Timothy H; Hampton, Craig R; Shimamoto, Akira; Mackman, Nigel; Verrier, Edward D

    2003-02-01

    Reperfusion of the ischemic heart is necessary to prevent irreversible injury of the myocardium, which leads to permanent organ dysfunction. However, reperfusion in itself leads to myocardial ischemia/reperfusion (I/R) injury, which is characterized by an acute inflammatory response mediated by activated inflammatory cells, chemokines, cytokines, and adhesion molecules. The molecular mechanisms of myocardial I/R injury are not completely known. Tissue factor (TF) and thrombin, two potent procoagulant and proinflammatory mediators, are recognized to play significant roles in myocardial I/R injury. To investigate the role of TF and thrombin in myocardial I/R injury, we used rabbit and murine in situ coronary artery ligation models. Increased TF mRNA, antigen, and activity were found in ischemic cardiomyocytes. Administration of an inhibitory antirabbit TF monoclonal antibody before or during the onset of ischemia resulted in a significant reduction in infarct size. Functional inhibition of thrombin with hirudin also reduced the infarct size. However, defibrinogenating rabbits with ancrod had no effect on infarct size, suggesting a requirement of thrombin generation but not fibrin deposition in myocardial I/R injury. PMID:12607707

  10. Endovascular Treatment of Chronic Mesenteric Ischemia: Results in 14 Patients

    SciTech Connect

    Chahid, Tamam; Alfidja, Agaicha T.; Biard, Marie; Ravel, Anne; Garcier, Jean Marc; Boyer, L.

    2004-11-15

    We evaluated immediate and long-term results of percutaneous transluminal angioplasty (PTA) and stent placement to treat stenotic and occluded arteries in patients with chronic mesenteric ischemia. Fourteen patients were treated by 3 exclusive celiac artery (CA) PTAs (2 stentings), 3 cases with both Superior Mesenteric Artery (SMA) and CA angioplasties, and 8 exclusive SMA angioplasties (3 stentings). Eleven patients had atheromatous stenoses with one case of an early onset atheroma in an HIV patient with antiphospholipid syndrome. The other etiologies of mesenteric arterial lesions were Takayashu arteritis (2 cases) and a postradiation stenoses (1 case). Technical success was achieved in all cases. Two major complications were observed: one hematoma and one false aneurysm occurring at the brachial puncture site (14.3%). An immediate clinical success was obtained in all patients. During a follow-up of 1-83 months (mean: 29 months), 11 patients were symptom free; 3 patients had recurrent pain; in one patient with inflammatory syndrome, pain relief was obtained with medical treatment; in 2 patients abdominal pain was due to restenosis 36 and 6 months after PTA, respectively. Restenosis was treated by PTA (postirradiation stenosis), and by surgical bypass (atheromatous stenosis). Percutaneous endovascular techniques are safe and accurate. They are an alternative to surgery in patients with chronic mesenteric ischemia due to short and proximal occlusive lesions of SMA and CA.

  11. Houshiheisan compound prescription protects neurovascular units after cerebral ischemia.

    PubMed

    Wang, Haizheng; Wang, Lei; Zhang, Nan; Zhang, Qi; Zhao, Hui; Zhang, Qiuxia

    2014-04-01

    Houshiheisan is composed of wind-dispelling (chrysanthemun flower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root) and deficiency-nourishing (ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber) drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immunofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regulated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-β 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-β 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance deposition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra. PMID:25206882

  12. Application of laser therapy in the treatment of brain ischemia

    NASA Astrophysics Data System (ADS)

    Zalesskaya, G. A.; Nechipurenko, N. I.; Musienko, J. I.; Kuchinsky, A. V.

    2007-06-01

    Intravenous laser irradiation of blood (ILIB) by helium-neon laser (HNL) with λ=632.8 nm, 2.5-4.5 mW at the light guide outlet was employed to investigate ILIB influence on blood oxygen transport (BOT), hydro-ion balance for normal rabbits and after modeling of local ischemia of brain (LIB). Marked improvement of disturbances typical for ischemia was revealed for both hydro-ion balance characteristics and BOT parameters such as oxygen tension (p vO II), oxygen hemoglobin saturation (s vO II), p vO II of blood under its 50% saturation by O II (p50) and tendency was found to their normalization. To identify the molecular photoacceptors and the mechanisms of primary photoreactions the spectral data were used both in visible and infrared regions. On the basis of spectral analysis hemoglobin was discussed as a possible photoacceptor when blood is irradiated with HNL radiation. Variations in the redox properties of respiratory chain components were considered as primary mechanisms of light action on photoacceptor molecules that initiated a cascade of secondary reactions controlling cellular homeostasis parameters.

  13. Blood biomarkers in the early stage of cerebral ischemia.

    PubMed

    Maestrini, I; Ducroquet, A; Moulin, S; Leys, D; Cordonnier, C; Bordet, R

    2016-03-01

    In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed. PMID:26988891

  14. Ischemia-induced Angiogenesis is Attenuated in Aged Rats

    PubMed Central

    Tang, Yaohui; Wang, Liuqing; Wang, Jixian; Lin, Xiaojie; Wang, Yongting; Jin, Kunlin; Yang, Guo-Yuan

    2016-01-01

    To study whether focal angiogenesis is induced in aged rodents after permanent distal middle cerebral artery occlusion (MCAO), young adult (3-month-old) and aged (24-month-old) Fisher 344 rats underwent MCAO and sacrificed up to two months after MCAO. Immunohistochemistry and synchrotron radiation microangiography were performed to examine the number of newly formed blood vessels in both young adult and aged rats post-ischemia. We found that the number of capillaries and small arteries in aged brain was the same as young adult brain. In addition, we found that after MCAO, the number of blood vessels in the peri-infarct region of ipsilateral hemisphere in aged ischemic rats was significantly increased compared to the aged sham rats (p<0.05). We also confirmed that ischemia-induced focal angiogenesis occurred in young adult rat brain while the blood vessel density in young adult ischemic brain was significantly higher than that in the aged ischemic brain (p<0.05). Our data suggests that focal angiogenesis in aged rat brain can be induced in response to ischemic brain injury, and that aging impedes brain repairing and remodeling after ischemic stroke, possible due to the limited response of angiogenesis. PMID:27493831

  15. Cardiac Dysfunction After Left Permanent Cerebral Focal Ischemia

    PubMed Central

    Min, Jiangyong; Farooq, Muhammad U.; Greenberg, Eric; Aloka, Feras; Bhatt, Archit; Kassab, Mounzer; Morgan, James P.; Majid, Arshad

    2010-01-01

    Background and Purpose Stroke can lead to cerebrogenic cardiac arrhythmias. We sought to investigate the effect of ischemic stroke on cardiac function in a mouse model of permanent middle cerebral artery occlusion (pMCAO). Methods Twenty-four hours after the induction of focal ischemia, cardiac function was measured in mice by endovascular catheterization of the heart. Immediately after hemodynamic measurements, mice were euthanized and brains were excised and sectioned to measure infarct volume and the severity of insular cortex injury. Myocardial damage was evaluated by hematoxylin-eosin staining. Serum and heart levels of norepinephrine (NE) were also determined. Results Cardiac dysfunction occurred in 9 out of 14 mice that underwent left pMCAO. In these 9 mice, the severity of left insular cortex lesion was greater than the mice with normal heart function. The serum and heart levels of NE were significantly higher in left pMCAO mice with heart dysfunction. Liner regression analysis indicates significant inverse correlation between the severity of left insular cortex damage and heart dysfunction. Mice that underwent right pMCAO did not exhibit cardiac dysfunction. Conclusions This study shows that left focal cerebral ischemia can produce cardiac dysfunction, which is associated with the extent of left insular cortex damage. Furthermore, mice exhibiting cardiac dysfunction had elevated levels of NE in the serum and heart. PMID:19443809

  16. Geriatric Nutritional Risk Index (GNRI) Independently Predicts Amputation Inchronic Criticallimb Ischemia (CLI)

    PubMed Central

    Luo, Han; Yang, Hongliu; Huang, Bin; Yuan, Ding; Zhu, Jingqiang; Zhao, Jichun

    2016-01-01

    Objective General malnutrition usually occurs in critical limb ischemia (CLI) patients because of shortness of appetite and sleeplessness leaded by chronic pain. And amputation frequently is end-point of CLI patients. So the aim of this study was to assess the predictive ability of Geriatric nutritional risk index (GNRI) for predicting amputation in patients with CLI. Methods A retrospective study was designed. Demographics, history, comorbidity, and risk factors for peripheral vascular disease of admitted patients, and laboratory study were documented. Patients’ height, weight and BMI were recorded. Amputation was identified as end-point during follow-up. Patients’ amputation-free survival (AFS) was recorded. Result 172 patients were identified, with mean age 71.98±3.12. Geriatric nutritional risk index (GNRI) = 90 was taken as cutoff value of high risk of amputation for CLI patients via using receiver operating characteristic (ROC) curve. Span of follow-up was 12–48 months. During follow-up, 60 patients (36.04%) received amputation surgery. And analyzed by Cox proportional hazards model, it is found that GNRI was the independent predictive factor for amputation in long term. Conclusion This study revealed that GNRI was a reliable and effective predictive marker for AFS. GNRI could identify patients with high risk for amputation in early time. PMID:27010532

  17. Mitochondrial targets for volatile anesthetics against cardiac ischemia-reperfusion injury

    PubMed Central

    Agarwal, Bhawana; Stowe, David F.; Dash, Ranjan K.; Bosnjak, Zeljko J.; Camara, Amadou K. S.

    2014-01-01

    Mitochondria are critical modulators of cell function and are increasingly recognized as proximal sensors and effectors that ultimately determine the balance between cell survival and cell death. Volatile anesthetics (VA) are long known for their cardioprotective effects, as demonstrated by improved mitochondrial and cellular functions, and by reduced necrotic and apoptotic cell death during cardiac ischemia and reperfusion (IR) injury. The molecular mechanisms by which VA impart cardioprotection are still poorly understood. Because of the emerging role of mitochondria as therapeutic targets in diseases, including ischemic heart disease, it is important to know if VA-induced cytoprotective mechanisms are mediated at the mitochondrial level. In recent years, considerable evidence points to direct effects of VA on mitochondrial channel/transporter protein functions and electron transport chain (ETC) complexes as potential targets in mediating cardioprotection. This review furnishes an integrated overview of targets that VA impart on mitochondrial channels/transporters and ETC proteins that could provide a basis for cation regulation and homeostasis, mitochondrial bioenergetics, and reactive oxygen species (ROS) emission in redox signaling for cardiac cell protection during IR injury. PMID:25278902

  18. The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage

    PubMed Central

    Østergaard, Leif; Aamand, Rasmus; Karabegovic, Sanja; Tietze, Anna; Blicher, Jakob Udby; Mikkelsen, Irene Klærke; Iversen, Nina Kerting; Secher, Niels; Engedal, Thorbjørn Søndergaard; Anzabi, Mariam; Jimenez, Eugenio Gutierrez; Cai, Changsi; Koch, Klaus Ulrik; Næss-Schmidt, Erhard Trillingsgaard; Obel, Annette; Juul, Niels; Rasmussen, Mads; Sørensen, Jens Christian Hedemann

    2013-01-01

    The mortality after aneurysmal subarachnoid hemorrhage (SAH) is 50%, and most survivors suffer severe functional and cognitive deficits. Half of SAH patients deteriorate 5 to 14 days after the initial bleeding, so-called delayed cerebral ischemia (DCI). Although often attributed to vasospasms, DCI may develop in the absence of angiographic vasospasms, and therapeutic reversal of angiographic vasospasms fails to improve patient outcome. The etiology of chronic neurodegenerative changes after SAH remains poorly understood. Brain oxygenation depends on both cerebral blood flow (CBF) and its microscopic distribution, the so-called capillary transit time heterogeneity (CTH). In theory, increased CTH can therefore lead to tissue hypoxia in the absence of severe CBF reductions, whereas reductions in CBF, paradoxically, improve brain oxygenation if CTH is critically elevated. We review potential sources of elevated CTH after SAH. Pericyte constrictions in relation to the initial ischemic episode and subsequent oxidative stress, nitric oxide depletion during the pericapillary clearance of oxyhemoglobin, vasogenic edema, leukocytosis, and astrocytic endfeet swelling are identified as potential sources of elevated CTH, and hence of metabolic derangement, after SAH. Irreversible changes in capillary morphology and function are predicted to contribute to long-term relative tissue hypoxia, inflammation, and neurodegeneration. We discuss diagnostic and therapeutic implications of these predictions. PMID:24064495

  19. Design and fabrication of nanowire electrodes on a flexible substrate for detection of myocardial ischemia

    NASA Astrophysics Data System (ADS)

    Ramachandran, Vasuda; Yoon, Hargsoon; Varadan, Vijay K.

    2009-03-01

    According to a report by the American Heart Association, there are approximately 3-4 million Americans that may experience silent Myocardial Ischemia (MI). Silent MI is a serious heart condition that can progress to a severe heart attack without any warning and the consequences of such an event can turn fatal quickly. Therefore, there is a strong need for a sensor that can continuously monitor the onset of the condition to prevent high risk individuals from deadly heart attacks. An increase in extracellular potassium levels is the first sign of MI and timely sensing with an implantable potassium sensing biosensor could play a critical role in detecting and expediting care. There are challenges in the development of an implantable potassium sensing electrode one of which includes signal drift. The incorporation of novel nanostructures and smarter materials hold the potential to combat these problems. This paper presents a unique design for an all-solid-state potassium sensing device which offers miniaturization along with enhanced signal transduction. These characteristics are important when it comes to implantable devices and signal drift. Sensor design details along with fabrication processes and sensing results are discussed.

  20. Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury

    PubMed Central

    Lee, Dongwon; Park, Seunggyu; Bae, Soochan; Jeong, Dahee; Park, Minhyung; Kang, Changsun; Yoo, Wooyoung; Samad, Mohammed A.; Ke, Qingen; Khang, Gilson; Kang, Peter M.

    2015-01-01

    Overproduction of hydrogen peroxide (H2O2) causes oxidative stress and is the main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury. Suppression of oxidative stress is therefore critical in the treatment of I/R injury. Here, we report H2O2-activatable antioxidant prodrug (BRAP) that is capable of specifically targeting the site of oxidative stress and exerting anti-inflammatory and anti-apoptotic activities. BRAP with a self-immolative boronic ester protecting group was designed to scavenge H2O2 and release HBA (p-hydroxybenzyl alcohol) with antioxidant and anti-inflammatory activities. BRAP exerted potent antioxidant and anti-inflammatory activity in lipopolysaccharide (LPS)- and H2O2-stimulated cells by suppressing the generation of ROS and pro-inflammatory cytokines. In mouse models of hepatic I/R and cardiac I/R, BRAP exerted potent antioxidant, anti-inflammatory and anti-apoptotic activities due to the synergistic effects of H2O2-scavenging boronic esters and therapeutic HBA. In addition, administration of high doses of BRAP daily for 7 days showed no renal or hepatic function abnormalities. Therefore BRAP has tremendous therapeutic potential as H2O2-activatable antioxidant prodrug for the treatment of I/R injuries. PMID:26563741

  1. Herbal compound Naoshuantong capsule attenuates retinal injury in ischemia/reperfusion rat model by inhibiting apoptosis

    PubMed Central

    Huang, Chuangxin; Gao, Yang; Yu, Qiang; Feng, Liangqi

    2015-01-01

    Objectives: Ischemic ophthalmopathy threatens people’s lives and health. The herbal compound medication, Naoshuantong capsule, plays a critical role in the treatment of cardiac-cerebral vascular diseases; however, the roles and mechanisms of action of Naoshuantong capsule in ischemic ophthalmopathy is unknown. The objective of the present study was to determine the effect and mechanism of action of Naoshuantong capsule on ischemic ophthalmopathy in rats. Methods: In this study a rat model of ischemic ophthalmopathy was constructed using a high intra-ocular pressure-induced ischemia/reperfusion model. The effects of Naoshuantong capsule on ischemic ophthalmopathy were detected using electroretinography, and changes in retinal ultrastructure were examined by HE staining and electron microscopy. The mechanism of action of Naoshuantong capsule on ischemic ophthalmopathy was explored by immunofluorescence and real-time PCR. Results: Rat models of ischemic ophthalmopathy were successfully constructed by intra-ocular hypertension, which presented decreased amplitudes of the electroretinogram (ERG-b) wave and total retinal thickness, intracellular damage, increased expression of Bax and caspase 3, and decreased expression of Bcl-2. Treatment with Naoshuantong capsule attenuated the changes and damage to the ischemic retina in the rat model, inhibited the over-expression of Bax and caspase 3, and increased the expression of Bcl-2. Conclusion: Our study indicated that Naoshuantong capsule attenuates retinal damage in rat models of ischemic ophthalmopathy, possibly by inhibiting apoptosis. PMID:26550135

  2. Toll-Like Receptors: New Players in Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Ha, Tuanzhu; Liu, Li; Kelley, Jim; Kao, Race; Williams, David

    2011-01-01

    Abstract Innate immune and inflammatory responses have been implicated in myocardial ischemia/reperfusion (I/R) injury. However, the mechanisms by which innate immunity and inflammatory response are involved in myocardial I/R have not been elucidated completely. Recent studies highlight the role of Toll-like receptors (TLRs) in the induction of innate immune and inflammatory responses. Growing evidence has demonstrated that TLRs play a critical role in myocardial I/R injury. Specifically, deficiency of TLR4 protects the myocardium from ischemic injury, whereas modulation of TLR2 induces cardioprotection against ischemic insult. Importantly, cardioprotection induced by modulation of TLRs involves activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, suggesting that there is a crosstalk between TLRs and PI3K/Akt signaling pathways. In addition, TLRs also associate with other coreceptors, such as macrophage scavenger receptors in the recognition of their ligands. TLRs are also involved in the induction of angiogenesis, modulation of stem cell function, and expression of microRNA, which are currently important topic areas in myocardial I/R. Understanding how TLRs contribute to myocardial I/R injury could provide basic scientific knowledge for the development of new therapeutic approaches for the treatment and management of patients with heart attack. Antioxid. Redox Signal. 15, 1875–1893. PMID:21091074

  3. Ischemia-Reperfusion Injury Enhances Lymphatic Endothelial VEGFR3 and Rejection in Cardiac Allografts.

    PubMed

    Dashkevich, A; Raissadati, A; Syrjälä, S O; Zarkada, G; Keränen, M A I; Tuuminen, R; Krebs, R; Anisimov, A; Jeltsch, M; Leppänen, V-M; Alitalo, K; Nykänen, A I; Lemström, K B

    2016-04-01

    Organ damage and innate immunity during heart transplantation may evoke adaptive immunity with serious consequences. Because lymphatic vessels bridge innate and adaptive immunity, they are critical in immune surveillance; however, their role in ischemia-reperfusion injury (IRI) in allotransplantation remains unknown. We investigated whether the lymphangiogenic VEGF-C/VEGFR3 pathway during cardiac allograft IRI regulates organ damage and subsequent interplay between innate and adaptive immunity. We found that cardiac allograft IRI, within hours, increased graft VEGF-C expression and lymphatic vessel activation in the form of increased lymphatic VEGFR3 and adhesion protein expression. Pharmacological VEGF-C/VEGFR3 stimulation resulted in early lymphatic activation and later increase in allograft inflammation. In contrast, pharmacological VEGF-C/VEGFR3 inhibition during cardiac allograft IRI decreased early lymphatic vessel activation with subsequent dampening of acute and chronic rejection. Genetic deletion of VEGFR3 specifically in the lymphatics of the transplanted heart recapitulated the survival effect achieved by pharmacological VEGF-C/VEGFR3 inhibition. Our results suggest that tissue damage rapidly changes lymphatic vessel phenotype, which, in turn, may shape the interplay of innate and adaptive immunity. Importantly, VEGF-C/VEGFR3 inhibition during solid organ transplant IRI could be used as lymphatic-targeted immunomodulatory therapy to prevent acute and chronic rejection. PMID:26689983

  4. Pluronic® L64-mediated stable HIF-1α expression in muscle for therapeutic angiogenesis in mouse hindlimb ischemia

    PubMed Central

    Song, Hongmei; Liu, Sijia; Li, Caixia; Geng, Yanyan; Wang, Gang; Gu, Zhongwei

    2014-01-01

    Intramuscular injection of plasmid DNA (pDNA) to express a therapeutic protein is a promising method for the treatment of many diseases. However, the therapeutic applications are usually hindered by gene delivery efficiency and expression level. In this study, critical factors in a pDNA-based gene therapy system, such as gene delivery materials, a therapeutic gene, and its regulatory elements, were optimized to establish an integrated system for the treatment of mouse hindlimb ischemia. The results showed that Pluronic® L64 (L64) was an efficient and safe material for gene delivery into mouse skeletal muscle. It also showed intrinsic ability to promote in vivo angiogenesis in a concentration-dependent manner, which might be through the activation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-regulated angiogenic factors. The combination of 0.1% L64 with a hybrid gene promoter (pSC) increased the gene expression level, elongated the gene expression duration, and enhanced the number of transfected muscle fibers. In mice ischemic limbs, a gene medicine (pSC-HIF1αtri/L64) composed of L64 and pSC-based expression plasmid encoding hypoxia-inducible factor 1-alpha triple mutant (HIF-1αtri), improved the expression of stable HIF-1α, and in turn, the expression of multiple angiogenic factors. As a result, the ischemic limbs showed accelerated function recovery, reduced foot necrosis, faster blood reperfusion, and higher capillary density. These results indicated that the pSC-HIF1αtri/L64 combination presented a potential and convenient venue for the treatment of peripheral vascular diseases, especially critical limb ischemia. PMID:25092975

  5. Let-7a gene knockdown protects against cerebral ischemia/reperfusion injury

    PubMed Central

    Wang, Zhong-kun; Liu, Fang-fang; Wang, Yu; Jiang, Xin-mei; Yu, Xue-fan

    2016-01-01

    The microRNA (miRNA) let-7 was one of the first miRNAs to be discovered, and is highly conserved and widely expressed among species. let-7 expression increases in brain tissue after cerebral ischemia/reperfusion injury; however, no studies have reported let-7 effects on nerve injury after cerebral ischemia/reperfusion injury. To investigate the effects of let-7 gene knockdown on cerebral ischemia/reperfusion injury, we established a rat model of cerebral ischemia/reperfusion injury. Quantitative reverse transcription-polymerase chain reaction demonstrated that 12 hours after cerebral ischemia/reperfusion injury, let-7 expression was up-regulated, peaked at 24 hours, and was still higher than that in control rats after 72 hours. Let-7 gene knockdown in rats suppressed microglial activation and inflammatory factor release, reduced neuronal apoptosis and infarct volume in brain tissue after cerebral ischemia/reperfusion injury. Western blot assays and luciferase assays revealed that mitogen-activated protein kinase phosphatase-1 (MKP1) is a direct target of let-7. Let-7 enhanced phosphorylated p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) expression by down-regulating MKP1. These findings suggest that knockdown of let-7 inhibited the activation of p38 MAPK and JNK signaling pathways by up-regulating MKP1 expression, reduced apoptosis and the inflammatory reaction, and exerted a neuroprotective effect following cerebral ischemia/reperfusion injury. PMID:27073379

  6. Fish oil prevents oxidative stress and exerts sustained antiamnesic effect after global cerebral ischemia.

    PubMed

    Bacarin, Cristiano Correia; de Sá-Nakanishi, Anacharis Babeto; Bracht, Adelar; Matsushita, Makoto; Santos Previdelli, Isolde; Mori, Marco Aurélio; de Oliveira, Rúbia Maria Weffort; Milani, Humberto

    2015-01-01

    Transient, global cerebral ischemia (TGCI) causes hippocampal/cortical damage and the persistent loss of welltrained, long-term memory (retrograde amnesia). Fish oil (FO), a rich source of omega-3 polyunsaturated fatty acids, abolishes such amnesia in the absence of neurohistological protection. The present study investigated whether FO prevents ischemia-induced oxidative stress and whether such an action contributes to the lasting effect of FO on memory recovery. In a first experiment, FO was administered for 4 days prior to ischemia, and antioxidant status was subsequently measured after 24 h of reperfusion. In another experiment, naive rats were trained in an eight-arm radial maze until they achieved asymptotic performance and then subjected to TGCI. One group of rats received FO as in the first experiment (i.e., 4 days prior to ischemia), whereas another group received FO for 4 days prior to ischemia plus 6 days postischemia. Retrograde memory performance was assessed 2-5 weeks after ischemia. TGCI depleted the level of antioxidant enzymes and increased the amount of protein carbonylation, indicating oxidative damage. Fish oil reversed oxidative damage to control levels. The same treatment that attenuated oxidative stress after 24 h of reperfusion also prevented retrograde amnesia assessed several weeks later. This antiamnesic effect afforded by short preischemia treatment was comparable to 10 days of treatment but not as consistent. These data indicate that an antioxidant action in the hyperacute phase of ischemia/reperfusion may contribute to the long-term, antiamnesic effect of FO. PMID:25714977

  7. Gastric injury induced by hemorrhage, local ischemia, and oxygen radical generation

    SciTech Connect

    Wadhwa, S.S.; Perry, M.A. )

    1987-08-01

    Gastric mucosal injury caused by local intra-arterial generation of oxygen-derived free radicals was compared with gastric injury caused by 30 min of hemorrhage-induced ischemia or local ischemia. The index of injury was the loss of {sup 51}Cr-labeled red cells across the gastric mucosa. Generation of oxygen radicals in the celiac artery caused a rapid increase in mucosal blood loss during the period of radical generation, and this loss was maintained after radical production ceased. Local ischemia produced similar mucosal injury; however, this occurred after reperfusion of the stomach and not during the ischemic episode. Hemorrhage-induced ischemia produced a threefold greater mucosal blood loss than local ischemia. The results of this study indicate that (1) oxygen radicals generated enzymatically in the blood supply to the stomach cause mucosal bleeding of similar magnitude to that observed after local ischemia and (2) that gastric ischemia induced by systemic hypotension produces more severe gastric injury than the same level of local hypotension.

  8. Ceramide is involved in triggering of cardiomyocyte apoptosis induced by ischemia and reperfusion.

    PubMed Central

    Bielawska, A. E.; Shapiro, J. P.; Jiang, L.; Melkonyan, H. S.; Piot, C.; Wolfe, C. L.; Tomei, L. D.; Hannun, Y. A.; Umansky, S. R.

    1997-01-01

    Involvement of ceramide signaling in the initiation of apoptosis induction in myocardial cells by in vitro and in vivo ischemia and reperfusion was analyzed. Synthetic cell permeable C2-ceramide induced apoptotic death of rat neonatal cardiomyocytes in vitro. In vitro ischemia (oxygen/serum/glucose deprivation) led to a progressive accumulation of ceramide in cardiomyocytes. After 16 hours of simulated in vitro reperfusion (readdition of oxygen, serum and glucose), the level of ceramide in surviving cells was found to have returned to baseline, whereas, levels in nonadherent dead cells remained high. In the rat heart left coronary artery occlusion model, ischemia with the subsequent reperfusion, but not ischemia alone, induced apoptosis in myocardial cells as demonstrated by DNA electrophoresis and measurement of soluble chromatin degradation products. The content of ceramide in ischemic area was elevated to 155% baseline levels at 30 minutes, and to 330% after 210 minutes of ischemia. Ischemia (30 minutes) followed by reperfusion (180 minutes) increased the ceramide level to 250% in the ischemic area. The combination of results obtained in both in vitro and animal models demonstrate for the first time that ceramide signaling can be involved in ischemia/reperfusion death of myocardial cells. Images Figure 2 Figure 4 PMID:9358751

  9. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils.

    PubMed

    Lee, Sang-Hak; Ko, Il-Gyu; Kim, Sung-Eun; Hwang, Lakkyong; Jin, Jun-Jang; Choi, Hyun-Hee; Kim, Chang-Ju

    2016-04-01

    Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2'-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury. PMID:27162767

  10. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils

    PubMed Central

    Lee, Sang-Hak; Ko, Il-Gyu; Kim, Sung-Eun; Hwang, Lakkyong; Jin, Jun-Jang; Choi, Hyun-Hee; Kim, Chang-Ju

    2016-01-01

    Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2′-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury. PMID:27162767

  11. Isolating the segment of the mitochondrial electron transport chain responsible for mitochondrial damage during cardiac ischemia

    SciTech Connect

    Chen, Qun; Yin, Guotian; Stewart, Sarah; Hu, Ying; Lesnefsky, Edward J.

    2010-07-09

    Ischemia damages the mitochondrial electron transport chain (ETC), mediated in part by damage generated by the mitochondria themselves. Mitochondrial damage resulting from ischemia, in turn, leads to cardiac injury during reperfusion. The goal of the present study was to localize the segment of the ETC that produces the ischemic mitochondrial damage. We tested if blockade of the proximal ETC at complex I differed from blockade distal in the chain at cytochrome oxidase. Isolated rabbit hearts were perfused for 15 min followed by 30 min stop-flow ischemia at 37 {sup o}C. Amobarbital (2.5 mM) or azide (5 mM) was used to block proximal (complex I) or distal (cytochrome oxidase) sites in the ETC. Time control hearts were buffer-perfused for 45 min. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated. Ischemia decreased cytochrome c content in SSM but not in IFM compared to time control. Blockade of electron transport at complex I preserved the cytochrome c content in SSM. In contrast, blockade of electron transport at cytochrome oxidase with azide did not retain cytochrome c in SSM during ischemia. Since blockade of electron transport at complex III also prevented cytochrome c loss during ischemia, the specific site that elicits mitochondrial damage during ischemia is likely located in the segment between complex III and cytochrome oxidase.

  12. Enhanced autophagy signaling in diabetic rats with ischemia-induced seizures.

    PubMed

    Xia, Luoxing; Lei, Zhigang; Shi, Zhongshan; Guo, Dave; Su, Henry; Ruan, Yiwen; Xu, Zao C

    2016-07-15

    Seizures are among the most common neurological sequelae of stroke, and ischemic insult in diabetes notably increases the incidence of seizures. Recent studies indicated that autophagy influences the outcome of stroke and involved in epileptogenesis. However, the association of autophagy and post-ischemic seizures in diabetes remains unclear. The present study aimed to reveal the involvement of autophagy in the seizures following cerebral ischemia in diabetes. Diabetes was induced in adult male Wistar rats by intraperitoneal injection of streptozotocin (STZ). The diabetic rats were subjected to transient forebrain ischemia. The neuronal damage was assessed using hematoxylin-eosin staining. Western blotting and immunohistochemistry were performed to investigate the alteration of autophagy marker microtubule-associated protein light chain 1B (LC3B). The results showed that all diabetic animals developed seizures after ischemia. However, no apparent cell death was observed in the hippocampus of seizure rats 12h after the insult. The expression of LC3B was significantly enhanced in naïve animals after ischemia and was further increased in diabetic animals after ischemia. Immunofluorescence double-labeling study indicated that LC3B was mainly increased in neurons. Our study demonstrated, for the first time, that autophagy activity is significantly increased in diabetic animals with ischemia-induced seizures. Further studies are needed to explore the role of autophagy in seizure generation after ischemia in diabetic conditions. PMID:27125597

  13. Diabetes Inhibits Cerebral Ischemia-Induced Astrocyte Activation - an Observation in the Cingulate Cortex

    PubMed Central

    Jing, Li; Mai, Li; Zhang, Jian-Zhong; Wang, Jian-Gang; Chang, Yue; Dong, Jian-Da; Guo, Feng-Ying; Li, P. Andy

    2013-01-01

    The objective of this study was to study the effect of diabetic hyperglycemia on astrocytes after forebrain ischemia. Streptozotocin (STZ)-injected hyperglycemic and vehicle-injected normoglycemic rats were subjected to 15 minutes of forebrain ischemia. The brains were harvested in sham-operated controls and in animals with 1 and 6 h of recirculation following ischemia. Brain damage was accessed by haematoxylin and eosin (H&E) staining, cleaved caspase-3 immunohistochemistry and TdT-mediated-dUTP nick end labeling (TUNEL). Anti-GFAP antibody was employed to study astrocytes. The results showed that the 15-minute ischemia caused neuronal death after 1 and 6 h of reperfusion as revealed by increased numbers of karyopyknotic cells, edema, TUNEL-positive and active caspase-3-positive cells. Ischemia also activated astrocytes in the cingulated cortex as reflected by astrocyte stomata hypertrophy, elongated dendrites and increases in the number of dendrites, and immunoreactivity of GFAP. Diabetic hyperglycemia further enhanced neuronal death and suppressed ischemia-induced astrocyte activation. Further, diabetes-damaged astrocytes have increased withdrawal of the astrocyte end-foot from the cerebral blood vessel wall. It is concluded that diabetes-induced suppression and damages to astrocytes may contribute to its detrimental effects on recovery from cerebral ischemia. PMID:24163590

  14. GABA and benzodiazepine receptors in the gerbil brain after transient ischemia: demonstration by quantitative receptor autoradiography

    SciTech Connect

    Onodera, H.; Sato, G.; Kogure, K.

    1987-02-01

    Quantitative receptor autoradiography was used to measure the binding of gamma-aminobutyric acid (GABA) and benzodiazepine receptors after ischemia by means of transient occlusion of bilateral common carotid arteries in the gerbil. (/sup 3/H)Muscimol was used to label the GABAA receptors and (/sup 3/H)flunitrazepam to label central type benzodiazepine receptors. In the superolateral convexities of the frontal cortices, (/sup 3/H)muscimol binding was increased in 60% of the animals killed 3 days after ischemia, and decreased in 67% of the animals killed 27 days after ischemia. Twenty-seven days after ischemia, (/sup 3/H)flunitrazepam binding in the substantia nigra pars reticulata increased to 252% of the control, though the increase in (/sup 3/H)muscimol binding was not significant. In the dorsolateral region of the caudate putamen, marked neuronal necrosis and depletion of both (/sup 3/H)muscimol and (/sup 3/H)flunitrazepam binding sites were observed 27 days after ischemia, the ventromedial region being left intact. In spite of the depletion of pyramidal cells in the CA1 region of the hippocampus, both (/sup 3/H)muscimol and (/sup 3/H)flunitrazepam binding sites were preserved 27 days after ischemia. Since our previous study revealed that adenosine A1 binding sites were depleted in the CA1 subfield of the hippocampus after ischemia correlating with neuronal damage, GABAA and benzodiazepine receptors may not be distributed predominantly on the pyramidal cells in the CA1 region.

  15. Towards a dynamical network view of brain ischemia and reperfusion. Part I: background and preliminaries

    PubMed Central

    DeGracia, Donald J.

    2011-01-01

    The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the “ischemic cascade”. This is the first in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. This first paper sets the stage for developing the bistable model of brain ischemia. Necessary background in network theory is introduced using examples from developmental biology which, perhaps surprisingly, can be adapted to brain ischemia with only minor modification. Then, to move towards a network model, we extract two core generalizations about brain ischemia from the mass of empirical data. First, we conclude that all changes induced in the brain by ischemia can be classified as either damage mechanisms that contribute to cell death, or stress responses that contribute to cell survival. Second, we move towards formalizing the idea of the “amount of ischemia”, I, as a continuous, nonnegative, monotonically increasing quantity. These two generalizations are necessary precursors to reformulating brain ischemia as a bistable network. PMID:21528102

  16. Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury.

    PubMed

    Kezic, Aleksandra; Spasojevic, Ivan; Lezaic, Visnja; Bajcetic, Milica

    2016-01-01

    Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury. PMID:27313826

  17. The Role of the Ubiquitin Proteasome System in Ischemia and Ischemic Tolerance

    PubMed Central

    Meller, Robert

    2010-01-01

    Ubiquitin modification targets a protein for rapid degradation by the proteasome. However, poly-ubiquitination of proteins can result in multiple functions depending on the topology of the ubiquitin chain. Therefore ubiquitin signaling offers a more complex and versatile biology compared to many other post translational modifications. One area of potential for the application of this knowledge is the field of ischemia-induced brain damage, as occurs following a stroke. The ubiquitin proteasome system may exert a dual role on neuronal outcome following ischemia. Harmful ischemia results in an overload of the ubiquitin proteasome system, and blocking the proteasome reduces brain infarction following ischemia. However, the rapid and selective degradation of proteins following brief ischemia results in endogenous protection against ischemia. Therefore further understanding of the molecular signaling mechanisms which regulate the ubiquitin proteasome system may reveal novel therapeutic targets to reduce brain damage when ischemia is predicted, or to reduce the activation of the cell death mechanisms and the inflammatory response following stroke. The aim of this review is to discuss some of the recent advances in the understanding of protein ubiquitination and its implications for novel stroke therapies. PMID:19181875

  18. Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury

    PubMed Central

    Kezic, Aleksandra; Spasojevic, Ivan; Lezaic, Visnja; Bajcetic, Milica

    2016-01-01

    Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury. PMID:27313826

  19. Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injury

    PubMed Central

    Wang, Baogang; Zhu, Qingsan; Man, Xiaxia; Guo, Li; Hao, Liming

    2014-01-01

    Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-dependently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reperfusion injury. These findings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression. PMID:25374589

  20. Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95.

    PubMed

    Zhou, Li; Li, Fei; Xu, Hai-Bing; Luo, Chun-Xia; Wu, Hai-Yin; Zhu, Ming-Mei; Lu, Wei; Ji, Xing; Zhou, Qi-Gang; Zhu, Dong-Ya

    2010-12-01

    Stroke is a major public health problem leading to high rates of death and disability in adults. Excessive stimulation of N-methyl-D-aspartate receptors (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation are crucial for neuronal injury after stroke insult. However, directly inhibiting NMDARs or nNOS can cause severe side effects because they have key physiological functions in the CNS. Here we show that cerebral ischemia induces the interaction of nNOS with postsynaptic density protein-95 (PSD-95). Disrupting nNOS-PSD-95 interaction via overexpressing the N-terminal amino acid residues 1-133 of nNOS (nNOS-N(1-133)) prevented glutamate-induced excitotoxicity and cerebral ischemic damage. Given the mechanism of nNOS-PSD-95 interaction, we developed a series of compounds and discovered a small-molecular inhibitor of the nNOS-PSD-95 interaction, ZL006. This drug blocked the ischemia-induced nNOS-PSD-95 association selectively, had potent neuroprotective activity in vitro and ameliorated focal cerebral ischemic damage in mice and rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion. Moreover, it readily crossed the blood-brain barrier, did not inhibit NMDAR function, catalytic activity of nNOS or spatial memory, and had no effect on aggressive behaviors. Thus, this new drug may serve as a treatment for stroke, perhaps without major side effects. PMID:21102461

  1. Critical Pedagogy for Critical Mathematics Education

    ERIC Educational Resources Information Center

    Tutak, Fatma Aslan; Bondy, Elizabeth; Adams, Thomasenia L.

    2011-01-01

    This article provides a brief introduction to critical pedagogy and further discussion on critical mathematics education. Critical mathematics education enables students to read the world with mathematics. Three emerging domains of mathematics education related to critical mathematics education are discussed in this manuscript: ethnomathematics,…

  2. Physiological ischemia/reperfusion phenomena and their relation to endogenous melatonin production: a hypothesis.

    PubMed

    Tan, Dun-Xian; Manchester, Lucien C; Sainz, Rosa M; Mayo, Juan C; León, Josefa; Reiter, Russel J

    2005-07-01

    Ischemia/reperfusion is a frequently encountered phenomenon in organisms. Prolonged ischemia followed then by reperfusion results in severe oxidative injury in tissues and organs; however, some species can tolerate such events better than others. In nature, arousal from hibernation and resurfacing from diving causes animals to experience classic ischemia/reperfusion and, somehow, these animals cope well with the potential oxidative stress. It has been documented that during these physiological ischemia/reperfusion events, the activities of several antioxidant enzymes and the levels of some small-molecular-weight antioxidants become elevated. For example, the potent small-molecular-weight antioxidant melatonin often attains especially high levels during these physiological ischemia/reperfusion events including during arousal from hibernation or in the newborns during delivery. Highly elevated melatonin production during these physiological ischemia/reperfusion episodes exhibits several features. First, this high melatonin production is transient and fits well with the time schedule of the physiological ischemia/reperfusion period; therefore, it is not related to the normal endogenous melatonin rhythm. Yet, this transient peak protects the animals from destructive oxidative processes that occur during these transition periods. Second, these high levels of melatonin seem to derive from several organs since pinealectomy does not totally reduce circulating levels of this agent. Third, high melatonin production present at arousal from hibernation or in the newborns at birth does not appear to be controlled by light, i.e., it occurs both during the day and at night, and the amplitudes of elevated melatonin levels are equivalent at these times. The significance of these findings is discussed herein. Based on currently available data, we hypothesize that melatonin plays an important role in the physiological ischemia/reperfusion, i.e., as a member of antioxidant defense

  3. Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice

    PubMed Central

    Zhang, Nannan; Ding, Shinghua

    2015-01-01

    Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca2+ signaling using two-photon microscopy. PMID:26274772

  4. Dictionary-Driven Ischemia Detection From Cardiac Phase-Resolved Myocardial BOLD MRI at Rest.

    PubMed

    Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A

    2016-01-01

    Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP-BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP-BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson's r=0.84) with respect to infarct size. When advances in automated registration and segmentation of CP-BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique. PMID:26292338

  5. Acute limb ischemia caused by incorrect deployment of a clip-based arterial closure device

    PubMed Central

    Dzieciuchowicz, Łukasz; Stefaniak, Karolina; Oszkinis, Grzegorz

    2016-01-01

    Failure of a vascular closure device most commonly results in a hemorrhage or pseudoaneurysm formation. In this paper a rare case of severe acute limb ischemia following incorrect deployment of a clip-based closure device (Starclose SE, Abbott Vascular) in a 31-year-old woman is presented. Symptoms of acute limb ischemia occurred at the start of the ambulation, 6 h after completion of the procedure. Because of the severity of ischemia the patient was treated surgically, and limb perfusion was successfully restored. An attempt of closure of an inadvertently punctured narrow superficial femoral artery was identified as the cause of this complication. PMID:27458492

  6. Antioxidant Stress and Anti-Inflammation of PPARα on Warm Hepatic Ischemia-Reperfusion Injury

    PubMed Central

    Gao, Zhixin; Li, Yuan-Hai

    2012-01-01

    Hepatic ischemia-reperfusion (IR) injury is a serious clinical problem. Minimizing the adverse effect of ischemia-reperfusion injury after liver surgery or trauma is an urgent need. It has been proved that besides the effect of regulating the lipid and lipoprotein metabolism, PPARα also undertakes the task of organ protection. In this paper, related literature has been summarized and we come to the conclusion that administration of PPARα agonists can strengthen the antioxidant and anti-inflammation defense system by the upregulation of the expression of antioxidant enzymes and inhibition of NF-κB activity. This may provide a potential clinical treatment for hepatic ischemia-reperfusion injury. PMID:23213319

  7. Diosmin Protects Rat Retina from Ischemia/Reperfusion Injury

    PubMed Central

    Tong, Nianting; Zhang, Zhenzhen; Gong, Yuanyuan; Yin, Lili

    2012-01-01

    Abstract Objective Diosmin, a natural flavone glycoside, possesses antioxidant activity and has been used to alleviate ischemia/reperfusion (I/R) injury. The aim of this study was to clarify whether the administration of diosmin has a protective effect against I/R injury induced using the high intraocular pressure (IOP) model in rat retina, and to determine the possible antioxidant mechanisms involved. Methods Retinal I/R injury was induced in the rats by elevating the IOP to 110 mmHg for 60 min. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. The levels of malondialdehyde (MDA) and the activities of total-superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the retinal tissues were determined 24 h after I/R injury. At 7 days post-I/R injury, electroretinograms (ERGs) were recorded, and the density of surviving retinal ganglion cells (RGCs) was estimated by counting retrograde tracer-labeled cells in whole-mounted retinas. Retinal histological changes were also examined and quantified using light microscopy. Results Diosmin significantly decreased the MDA levels and increased the activities of T-SOD, GSH-Px, and CAT in the retina of rats compared with the ischemia group (P<0.05), and suppressed the I/R-induced reduction in the a- and b-wave amplitudes of the ERG (P<0.05). The thickness of the entire retina, inner nuclear layer, inner plexiform layer, and outer retinal layer and the number of cells in the ganglion cell layer were significantly less after I/R injury (P<0.05), and diosmin remarkably ameliorated these changes on retinal morphology. Diosmin also attenuated the I/R-induced loss of RGCs of the rat retina (P<0.05). Conclusion Diosmin protected the retina from I/R injury, possibly via a mechanism involving the regulation of oxidative parameters. PMID:22509733

  8. Adropin reduces paracellular permeability of rat brain endothelial cells exposed to ischemia-like conditions.

    PubMed

    Yang, Changjun; DeMars, Kelly M; Hawkins, Kimberly E; Candelario-Jalil, Eduardo

    2016-07-01

    Adropin is a peptide encoded by the energy homeostasis associated gene (Enho) and plays a critical role in the regulation of lipid metabolism, insulin sensitivity, and endothelial function. Little is known of the effects of adropin in the brain and whether this peptide modulates ischemia-induced blood-brain barrier (BBB) injury. Here, we used an in vitro BBB model of rat brain microvascular endothelial cells (RBE4) and hypothesized that adropin would reduce endothelial permeability during ischemic conditions. To mimic ischemic conditions in vitro, RBE4 cell monolayers were subjected to 16h hypoxia/low glucose (HLG). This resulted in a significant increase in paracellular permeability to FITC-labeled dextran (40kDa), a dramatic upregulation of vascular endothelial growth factor (VEGF), and the loss of junction proteins occludin and VE-cadherin. Notably, HLG also significantly decreased Enho expression and adropin levels. Treatment of RBE4 cells with synthetic adropin (1, 10 and 100ng/ml) concentration-dependently reduced endothelial permeability after HLG, but this was not mediated through protection to junction proteins or through reduced levels of VEGF. We found that HLG dramatically increased myosin light chain 2 (MLC2) phosphorylation in RBE4 cells, which was significantly reduced by adropin treatment. We also found that HLG significantly increased Rho-associated kinase (ROCK) activity, a critical upstream effector of MLC2 phosphorylation, and that adropin treatment attenuated that effect. These data indicate that treatment with adropin reduces endothelial cell permeability after HLG insult by inhibition of the ROCK-MLC2 signaling pathway. These promising findings suggest that adropin protects against endothelial barrier dysfunction during ischemic conditions. PMID:27020249

  9. Preconditioning with recombinant high-mobility group box 1 induces ischemic tolerance in a rat model of focal cerebral ischemia-reperfusion.

    PubMed

    Wang, Chen; Liu, Xiao-Xi; Huang, Kai-Bin; Yin, Su-Bing; Wei, Jing-Jing; Hu, Ya-Fang; Gu, Yong; Zheng, Guo-Qing

    2016-05-01

    Preconditioning with ligands of toll-like receptors (TLRs) is a powerful neuroprotective approach whereby a low dose of stimulus confers significant protection against subsequent substantial brain damage by reprogramming the ischemia-activated TLRs signaling. Herein, we aim to explore whether preconditioning with recombinant high-mobility group box 1 (rHMGB1), one of the TLRs ligands, decreases cerebral ischemia-reperfusion injury (IRI). Rats were intracerebroventricularly pretreated with rHMGB1, 1 or 3 days before induction of middle cerebral artery occlusion. Results showed that preconditioning with rHMGB1 1 day, but not 3 days, prior to ischemia dramatically reduced neurological deficits, infarct size, brain swelling, cell apoptosis, and blood-brain barrier permeability. Interleukin-1R-associated kinase-M (IRAK-M), a critical negative regulator of TLRs signaling, was robustly increased in response to brain IRI and was further elevated by rHMGB1 pretreatment, indicating its role associated with the rHMGB1 preconditioning-mediated ischemic tolerance. In vitro and in vivo assays indicated that the induced IRAK-M expression was localized in microglia. In addition, TLR4 specific inhibitor TAK-242 abolished the neuroprotective effects and the induction of IRAK-M offered by rHMGB1 preconditioning. Collectively, our study demonstrates that rHMGB1 preconditioning is neuroprotective during cerebral IRI, which is associated with activated TLR4/IRAK-M signaling in microglia. We found that high-mobility group box 1 (HMGB1) pretreatment conditioned the brain against subsequent ischemia-reperfusion injury. We propose the following mechanism for HMGB1 preconditioning-mediated ischemic tolerance: through toll-like receptor TLR4, HMGB1 preconditioning magnifies the up-regulation of interleukin-1R-associated kinase-M (IRAK-M) induced by ischemia-reperfusion in microglia, resulting in the decreased phosphorylation of IRAK-1. These findings are helpful in understanding the

  10. Renal ischemia/reperfusion injury; from pathophysiology to treatment

    PubMed Central

    Malek, Maryam; Nematbakhsh, Mehdi

    2015-01-01

    Ischemia/reperfusion injury (IRI) is caused by a sudden temporary impairment of the blood flow to the particular organ. IRI usually is associated with a robust inflammatory and oxidative stress response to hypoxia and reperfusion which disturbs the organ function. Renal IR induced acute kidney injury (AKI) contributes to high morbidity and mortality rate in a wide range of injuries. Although the pathophysiology of IRI is not completely understood, several important mechanisms resulting in kidney failure have been mentioned. In ischemic kidney and subsequent of re-oxygenation, generation of reactive oxygen species (ROS) at reperfusion phase initiates a cascade of deleterious cellular responses leading to inflammation, cell death, and acute kidney failure. Better understanding of the cellular pathophysiological mechanisms underlying kidney injury will hopefully result in the design of more targeted therapies to prevent and treatment the injury. In this review, we summarize some important potential mechanisms and therapeutic approaches in renal IRI. PMID:26060833

  11. Digital ischemia: angiographic differentiation of embolism from primary arterial disease

    SciTech Connect

    Maiman, M.H.; Bookstein, J.J.; Bernstein, E.F.

    1981-12-01

    Embolic disease is often overlooked as a cause of digital ischemia. Unilateral symptoms, in particular, should suggest the possibility of emboli arising from the subclavian or more distal upper extremity vessels. Emboli may originate in the subclavian artery as the result of atherosclerosis at its origin or arterial injury secondary to thoracic outlet compression. Arteriography can be useful in the identification of upper extremity emboli and their source, and should include studies of the aortic, arch, proximal subclavian artery, and digital arteries. Retrograde subclavian injections may be required to adequately demonstrate the origin of the subclavian artery. Magnification technique is often essential in differentiating small digital artery emboli from primary arterial diseases, such as Buerger disease or scleroderma.

  12. Treatment of acute limb ischemia with focus on endovascular techniques.

    PubMed

    Zeller, T; Tepe, G

    2009-05-01

    Acute limb ischemia is still the most frequent cause of major limb loss. Timely and fast revascularization is the key for limb salvage and patient survival. Large randomized trials showed equivalency of surgical and endovascular revascularization by means of local lysis with urokinase (TOPAS, STILE). New lytic agents and their modified application such as via a pulse spray catheter or combined with an ultrasound catheter and the combination with glycoprotein IIb/IIIa receptor antagonists have increased the efficacy and speed of thrombolysis. Recently, mechanical thrombectomy devices have become more widespread because intervention time and bleeding complications can be reduced. This review article summarizes the clinical presentation of and the treatment options for acute arterial occlusive disease caused either by embolism or local thrombosis. PMID:19588300

  13. Inflammatory response and neuronal necrosis in rats with cerebral ischemia

    PubMed Central

    Wu, Lingfeng; Zhang, Kunnan; Hu, Guozhu; Yan, Haiyu; Xie, Chen; Wu, Xiaomu

    2014-01-01

    In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis appeared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia. PMID:25422636

  14. [Programmed necrosis: a new target for
ischemia reperfusion injury].

    PubMed

    Li, Xiaojing; Ming, Yingzi; Niu, Ying; Liu, Qianwen; Ye, Qifa

    2016-07-01

    Recent years, the researchers have found a new type of cell death, referred to programmed necrosis or necroptosis, which involves the death receptor and the ligand binds and is initiated under the inhibition of apoptosis pathway. Programmed necrosis possesses the morphological features of typical necrosis accompanied by inflammation. The receptor interacting protein kinase 1/3(RIPK1/3) can be inhibited by the specific inhibitors, such as necrostatin-1. RIPK1/3 could regulate programmed necrosis and play a key role in the process. The significance of programmed necrosis in ischemia-reperfusion injury (IRI) has been attracted great attention at present. Simultaneously, a series of studies have found it also involves in the IRI of heart, kidney, brain and retina. PMID:27592584

  15. Cocaine-induced vasospasm causing spinal cord transient ischemia.

    PubMed

    Gorelik, N; Tampieri, D

    2012-07-01

    A 25-year-old woman developed a spinal cord infarction leading to quadriplegia and respiratory insufficiency after consuming cocaine and vodka for several days. Within five months, she regained full motor and respiratory function. A literature review revealed 11 cases of cocaine-induced spinal cord infarction. A complete recovery from quadriplegia and respiratory failure following cocaine abuse has never been reported to date. The value of diffusion-weighted imaging in cocaine-induced spinal cord infarction is here presented and discussed. The literature proposes several mechanisms for cocaine-induced infarction including vasospasm, arteritis, and thrombosis. In this case, the imaging studies and the full recovery suggest that the spinal cord ischemia was secondary to a transient vasospasm of the anterior spinal artery. PMID:24028991

  16. Role of Hydrogen Sulfide in Ischemia-Reperfusion Injury

    PubMed Central

    Wu, Dongdong; Wang, Jun; Li, Hui; Xue, Mengzhou; Ji, Ailing; Li, Yanzhang

    2015-01-01

    Ischemia-reperfusion (I/R) injury is one of the major causes of high morbidity, disability, and mortality in the world. I/R injury remains a complicated and unresolved situation in clinical practice, especially in the field of solid organ transplantation. Hydrogen sulfide (H2S) is the third gaseous signaling molecule and plays a broad range of physiological and pathophysiological roles in mammals. H2S could protect against I/R injury in many organs and tissues, such as heart, liver, kidney, brain, intestine, stomach, hind-limb, lung, and retina. The goal of this review is to highlight recent findings regarding the role of H2S in I/R injury. In this review, we present the production and metabolism of H2S and further discuss the effect and mechanism of H2S in I/R injury. PMID:26064416

  17. Does knee replacement surgery lead to chronic limb ischemia?

    PubMed

    Dawson, Alan G; Bachoo, Paul; Sutherland, Alasdair G

    2010-12-01

    Total knee replacement (TKR) may be associated with chronic limb ischemia (CLI) due to arterial injury intraoperatively. The aim of this study was to determine the incidence of CLI after TKR surgery. Patients who received a unilateral TKR in 2003-2004 were identified from our database. Patients with diabetes mellitus and preexisting peripheral arterial disease were excluded. Patient assessment was by collection of demographic details, completion of the Oxford Knee Score, Short Form-12 Health Survey, and King's College Hospital's Vascular Quality of Life Questionnaire, and measurement of the ankle brachial pressure index (ABPI). Of the 209 eligible patients, 86 (41%) participated (median age, 73 years; 50% male). Five (5.8%) patients had a reduced ABPI compared with population norms of 4.6 to 7%. Patients with reduced ABPI measurements had higher Oxford Knee Scores, but no relationships between other variables were demonstrated. TKR surgery does not appear to increase the risk of CLI. PMID:21446628

  18. Protective Effect of Tetramethylpyrazine on Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Qian, Weidong; Xiong, Xingjiang; Fang, Zhuyuan; Lu, Haiting; Wang, Zhensheng

    2014-01-01

    Myocardial ischemia-reperfusion injury (MIRI) is a common pathological and physiological phenomenon. Tetramethylpyrazine is the extract of the traditional Chinese medicine Chuanxiong, which can exert protective effects on MIRI in multiple ways. This paper reviewed the current research progress and evidence about the cardiovascular effects of tetramethylpyrazine, which included protecting mitochondria and improving energy metabolism, scavenging oxygen free radicals (OFRs) to inhibit lipid peroxidation, attenuating calcium (Ca2+) overload and maintaining Ca2+ homeostasis in cells, inhibiting apoptosis and protecting myocardial cells, interfering with the inflammatory reaction and mitigating cell injury, interfering with cell signaling pathways, and improving function of endothelial cells and protecting myocardial cells. However, further rigorously designed randomized controlled trials are warranted. PMID:25152756

  19. Ischemia detection by electrocardiogram in wavelet domain using entropy measure

    PubMed Central

    Rabbani, Hossein; Mahjoob, Mohammad Parsa; Farahabadi, Eiman; Farahabadi, Amin; Dehnavi, Alireza Mehri

    2011-01-01

    BACKGROUND: Ischemic heart disease is one of the common fatal diseases in advanced countries. Because signal perturbation in healthy people is less than signal perturbation in patients, entropy measure can be used as an appropriate feature for ischemia detection. METHODS: Four entropy-based methods comprising of using electrocardiogram (ECG) signal directly, wavelet sub-bands of ECG signals, extracted ST segments and reconstructed signal from time-frequency feature of ST segments in wavelet domain were investigated to distinguish between ECG signal of healthy individuals and patients. We used exercise treadmill test as a gold standard, with a sample of 40 patients who had ischemic signs based on initial diagnosis of medical practitioner. RESULTS: The suggested technique in wavelet domain resulted in the highest discrepancy between healthy individuals and patients in comparison to other methods. Specificity and sensitivity of this method were 95% and 94% respectively. CONCLUSIONS: The method based on wavelet sub-bands outperformed the others. PMID:22973350

  20. Ergotism With Ischemia In All Four Extremities: A Case Report

    PubMed Central

    Jeong, Seok-Young; Lim, Eui-Seong; Shin, Byoung-Soo; Seo, Man-Wook; Kim, Young-Hyun; Kwak, Hyo-Sung; Chung, Gyung-Ho

    2006-01-01

    Here we describe a case of ergotism that presented with ischemia in all four extremities. A 48-year-old man was admitted for pain and weakness in both upper extremities. He had a long history of migraine and had taken 3 mg of ergotamine daily for more than 21 years. Angiography demonstrated vasospasm involving all four extremities, which resolved partially following intra-arterial prostaglandin infusion. Intravenous nitroprusside was administered, and the patient stopped smoking and stopped taking ergotamine in an attempt to counteract the vasospasm. Follow-up computed tomography angiogram revealed that both brachial arteries had normalized. Thus, in this case of ergotism, severe vasospasm in all of the extremities was resolved with appropriate management. PMID:20396534

  1. Fulminant Nonocclusive Mesenteric Ischemia Just after Hip Arthroplasty

    PubMed Central

    Auxiliadora-Martins, Maria; Alkmin-Teixeira, Gil Cezar; Feres, Omar; Martins-Filho, Olindo Assis; Basile-Filho, Anibal

    2010-01-01

    Nonocclusive mesenteric ischemia (NOMI) is not a rare clinical entity in intensive medicine, and it can be a consequence of several clinical or surgical situations. This pathology results from reduced intestinal microvascular blood supply associated with an acute inflammatory process, culminating with bowel necrosis. This is a case on a female patient who developed immediate postsurgical NOMI following hip arthroplasty and died. Since diagnosis of this potentially fatal condition remains a dilemma, NOMI should always be considered an eventual postoperative complication in high-risk surgical patients such as elderly individuals with previous history of nicotine abuse, congestive heart failure, and essential hypertension. The present paper highlights the importance of early diagnosis and prompt adequate treatment of NOMI in subjects with diminished cardiac output and severe abdominal pain. PMID:20300426

  2. [Value of the exercise test in asymptomatic myocardial ischemia].

    PubMed

    Iturralde, P; Hernández, D; de Micheli, A; Colín, L; Romero, L; Villarreal, A; Férez, S; Miguel Casanova, J; Barrera, M; González-Hermosillo, J A

    1990-01-01

    To evaluate the predictive value of ischemic ST segment depression without associated chest pain during exercise testing, data were analyzed from 7305 studies. Two hundred thirty six patients were included in this study and were separated in 2 groups. Group A consisted of 169 patients without chest pain who, during exercise testing, showed a positive ST segment response (at least 1.5 mm of horizontal or downward ST segment depression for at least 0.08 second, compared with the resting baseline value), and Group B consisted of 67 patients who had both chest pain and a positive ST segment response. Selective coronary angiogram was performed on all patients. Each Group was separated into 3 sub-group according to the Cohn criteria: sub-group I (asymptomatic persons 8.3 vs 19.4%); sub-group II (patients with history of Myocardial Infarction 36.7% vs 19.4%); sub-group III (patients with chronic angina 55% vs 61.2%). The clinical characteristics, coronary risk factors, distribution of coronary artery disease, and exercise test response were similar in both groups. During treadmill exercise, the mean heart rate was 140.6 +/- 22 in group A versus 127.1 +/- 23 in the group B. The pressure-rate product was 2.4 +/- 0.8 versus 1.9 +/- 0.5, respectively (P less than or equal to 0.05). The predictive value for severe coronary artery disease of an exercise test in patients with asymptomatic ischemia was 77.5% as compared with 89.6% in the group with angina. This study confirms the high frequency of asymptomatic myocardial ischemia during exercise testing, compared with patients who had angina during exercise testing, with high percentage of prediction (77.5%) for coronary artery disease. PMID:2344225

  3. Ischemia--reperfusion: a look from yeast mitochondria.

    PubMed

    Stella, Carlos; Burgos, Isabel; Chapela, S; Gamondi, Oliver

    2011-01-01

    The apoptotic phenomena observed in tissues which are subdued to ischemia and then to technical therapeutics of perfusion keep causing serious problems in the patient's clinical recovery. Then, they constitute a challenge to resolve. The objective of this work is to discuss the intracellular mechanisms that lead cells to apoptosis during the ischemia-reperfusion process, taking into consideration that these phenomena are observable in a simple microorganism as the yeast Saccharomyces cerevisiae. Yeast provide an alternative study system in which the effects of certain cytoprotective drugs can be evaluated. The results can then be extrapolated to other types of cells. Several works have focused on the role of mitochondria in the apoptotic processes of cellular necrosis. One of the main factors responsible for this process is the unregulated opening of the permeability barrier. The inner membrane thus allows the unrestricted passage of ions and the release of apoptotic mediators from the inner membrane space towards the cytosol. Also, there is an increase in the level of reactive oxygen species (ROS) and the uncoupling of oxidative phosphorylation, which lead to the reversal of ATP synthesis to ATP hydrolysis. The driving cause of this complex process is the opening of an non-specific pore located in the mitochondrial membrane, denominated mammalian permeability transition pore (mPTP), which is also expressed in yeast (yPTP). From the functional point of view, the yeast pore presents some of the characteristics observed in mammals, and is similar in the defensive response against the deleterious mechanisms caused by oxidative stress. An increasing body of evidence supports the concept that the pharmacological inhibition of the mPTP is an actual and promising strategy for the protection of tissues in ischemic situations in order to avoid the damage induced by perfusion. PMID:21756235

  4. Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury

    PubMed Central

    Lempiäinen, Juha; Finckenberg, Piet; Mervaala, Elina E; Storvik, Markus; Kaivola, Juha; Lindstedt, Ken; Levijoki, Jouko; Mervaala, Eero M

    2014-01-01

    Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (α2-AR) agonist, protects against kidney I/R injury. Sprague–Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μg/kg). The effects of Dex postconditiong (Dex 1 or 10 μg/kg i.v. after reperfusion) as well as the effects of peripheral α2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre- nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning. PMID:25505591

  5. Prenatal cerebral ischemia triggers dysmaturation of caudate projection neurons

    PubMed Central

    McClendon, Evelyn; Chen, Kevin; Gong, Xi; Sharifnia, Elica; Hagen, Matthew; Cai, Victor; Shaver, Daniel C.; Riddle, Art; Dean, Justin M.; Gunn, Alistair J.; Mohr, Claudia; Kaplan, Joshua S.; Rossi, David J.; Kroenke, Christopher D.; Hohimer, A. Roger; Back, Stephen A.

    2014-01-01

    Objective Recently we reported that the neocortex displays impaired growth after transient cerebral hypoxia-ischemia (HI) at preterm gestation that is unrelated to neuronal death but is associated with decreased dendritic arbor complexity of cortical projection neurons. We hypothesized that these morphological changes constituted part of a more widespread neuronal dysmaturation response to HI in the caudate nucleus (CN), which contributes to motor and cognitive disability in preterm survivors. Methods Ex vivo magnetic resonance imaging (MRI), immunohistochemistry and Golgi staining defined CN growth, cell death, proliferation and dendritic maturation in preterm fetal sheep four weeks after HI. Patch-clamping recording was used to analyze glutamatergic synaptic currents in CN neurons. Results MRI-defined growth of the CN was reduced after ischemia compared to controls. However, no significant acute or delayed neuronal death was seen in the CN or white matter. Neither was there significant loss of calbindin-positive medium spiny projection neurons (MSNs) or CN interneurons expressing somatostatin, calretinin, parvalbumin, or tyrosine hydroxylase. Morphologically, ischemic MSNs showed a markedly immature dendritic arbor, with fewer dendritic branches, nodes, endings and spines. The magnitude and kinetics of synaptic currents, and the relative contribution of glutamate receptor subtypes in the CN were significantly altered. Interpretation The marked MSN dendritic and functional abnormalities after preterm cerebral HI, despite the marked resistance of immature CN neurons to cell death, are consistent with widespread susceptibility of projection neurons to HI-induced dysmaturation. These global disturbances in dendritic maturation and glutamatergic synaptic transmission suggest a new mechanism for long-term motor and behavioral disabilities in preterm survivors via widespread disruption of neuronal connectivity. PMID:24395459

  6. Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia

    PubMed Central

    Dobierzewska, Aneta; España-Perrot, Pedro P.; Venegas-Araneda, Pía; Guzmán-Rojas, Alejandra M.; González, María I.; Palominos-Rivera, Macarena; Irarrazabal, Carlos E.; Figueroa-Diesel, Horacio; Varas-Godoy, Manuel; Illanes, Sebastián E.

    2015-01-01

    Introduction Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE. Methods Serum samples were collected at 32–36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16) and pregnant controls (n = 32). The effect of oxygen tension on placental cells was assessed by incubation JEG–3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6) were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels). Aromatase content and estrogens and androgens concentrations were measured. Results The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG–3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be

  7. Mesenteric ischemia: Pathogenesis and challenging diagnostic and therapeutic modalities.

    PubMed

    Mastoraki, Aikaterini; Mastoraki, Sotiria; Tziava, Evgenia; Touloumi, Stavroula; Krinos, Nikolaos; Danias, Nikolaos; Lazaris, Andreas; Arkadopoulos, Nikolaos

    2016-02-15

    Mesenteric ischemia (MI) is an uncommon medical condition with high mortality rates. ΜΙ includes inadequate blood supply, inflammatory injury and eventually necrosis of the bowel wall. The disease can be divided into acute and chronic MI (CMI), with the first being subdivided into four categories. Therefore, acute MI (AMI) can occur as a result of arterial embolism, arterial thrombosis, mesenteric venous thrombosis and non-occlusive causes. Bowel damage is in proportion to the mesenteric blood flow decrease and may vary from minimum lesions, due to reversible ischemia, to transmural injury, with subsequent necrosis and perforation. CMI is associated to diffuse atherosclerotic disease in more than 95% of cases, with all major mesenteric arteries presenting stenosis or occlusion. Because of a lack of specific signs or due to its sometime quiet presentation, this condition is frequently diagnosed only at an advanced stage. Computed tomography (CT) imaging and CT angiography contribute to differential diagnosis and management of AMI. Angiography is also the criterion standard for CMI, with mesenteric duplex ultrasonography and magnetic resonance angiography also being of great importance. Therapeutic approach of MI includes both medical and surgical treatment. Surgical procedures include restoration of the blood flow with arteriotomy, endarterectomy or anterograde bypass, while resection of necrotic bowel is always implemented. The aim of this review was to evaluate the results of surgical treatment for MI and to present the recent literature in order to provide an update on the current concepts of surgical management of the disease. Mesh words selected include MI, diagnostic approach and therapeutic management. PMID:26909235

  8. Mesenteric ischemia: Pathogenesis and challenging diagnostic and therapeutic modalities

    PubMed Central

    Mastoraki, Aikaterini; Mastoraki, Sotiria; Tziava, Evgenia; Touloumi, Stavroula; Krinos, Nikolaos; Danias, Nikolaos; Lazaris, Andreas; Arkadopoulos, Nikolaos

    2016-01-01

    Mesenteric ischemia (MI) is an uncommon medical condition with high mortality rates. ΜΙ includes inadequate blood supply, inflammatory injury and eventually necrosis of the bowel wall. The disease can be divided into acute and chronic MI (CMI), with the first being subdivided into four categories. Therefore, acute MI (AMI) can occur as a result of arterial embolism, arterial thrombosis, mesenteric venous thrombosis and non-occlusive causes. Bowel damage is in proportion to the mesenteric blood flow decrease and may vary from minimum lesions, due to reversible ischemia, to transmural injury, with subsequent necrosis and perforation. CMI is associated to diffuse atherosclerotic disease in more than 95% of cases, with all major mesenteric arteries presenting stenosis or occlusion. Because of a lack of specific signs or due to its sometime quiet presentation, this condition is frequently diagnosed only at an advanced stage. Computed tomography (CT) imaging and CT angiography contribute to differential diagnosis and management of AMI. Angiography is also the criterion standard for CMI, with mesenteric duplex ultrasonography and magnetic resonance angiography also being of great importance. Therapeutic approach of MI includes both medical and surgical treatment. Surgical procedures include restoration of the blood flow with arteriotomy, endarterectomy or anterograde bypass, while resection of necrotic bowel is always implemented. The aim of this review was to evaluate the results of surgical treatment for MI and to present the recent literature in order to provide an update on the current concepts of surgical management of the disease. Mesh words selected include MI, diagnostic approach and therapeutic management. PMID:26909235

  9. Monocarboxylate transporter 4 plays a significant role in the neuroprotective mechanism of ischemic preconditioning in transient cerebral ischemia.

    PubMed

    Hong, Seongkweon; Ahn, Ji Yun; Cho, Geum-Sil; Kim, In Hye; Cho, Jeong Hwi; Ahn, Ji Hyeon; Park, Joon Ha; Won, Moo-Ho; Chen, Bai Hui; Shin, Bich-Na; Tae, Hyun-Jin; Park, Seung Min; Cho, Jun Hwi; Choi, Soo Young; Lee, Jae-Chul

    2015-10-01

    Monocarboxylate transporters (MCTs), which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ischemic preconditioning (IPC) on MCT4 immunoreactivity after 5 minutes of transient cerebral ischemia in the gerbil. Animals were randomly designated to four groups (sham-operated group, ischemia only group, IPC + sham-operated group and IPC + ischemia group). A serious loss of neuron was found in the stratum pyramidale of the hippocampal CA1 region (CA1), not CA2/3, of the ischemia-only group at 5 days post-ischemia; however, in the IPC + ischemia groups, neurons in the stratum pyramidale of the CA1 were well protected. Weak MCT4 immunoreactivity was found in the stratum pyramidale of the CA1 in the sham-operated group. MCT4 immunoreactivity in the stratum pyramidale began to decrease at 2 days post-ischemia and was hardly detected at 5 days post-ischemia; at this time point, MCT4 immunoreactivity was newly expressed in astrocytes. In the IPC + sham-operated group, MCT4 immunoreactivity in the stratum pyramidale of the CA1 was increased compared with the sham-operated group, and, in the IPC + ischemia group, MCT4 immunoreactivity was also increased in the stratum pyramidale compared with the ischemia only group. Briefly, present findings show that IPC apparently protected CA1 pyramidal neurons and increased or maintained MCT4 expression in the stratum pyramidale of the CA1 after transient cerebral ischemia. Our findings suggest that MCT4 appears to play a significant role in the neuroprotective mechanism of IPC in the gerbil with transient cerebral ischemia. PMID:26692857

  10. Failure in neuroprotection of remote limb ischemic postconditioning in the hippocampus of a gerbil model of transient cerebral ischemia.

    PubMed

    Lee, Jae-Chul; Tae, Hyun-Jin; Chen, Bai Hui; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Park, Joon Ha; Shin, Bich-Na; Lee, Hui Young; Cho, Young Shin; Cho, Jun Hwi; Hong, Seongkweon; Choi, Soo Young; Won, Moo-Ho; Park, Chan Woo

    2015-11-15

    Remote ischemic postconditioning (RIPoC) has been proven to provide potent protection of the heart and brain against ischemia-reperfusion injury. However, despite the evidence of cerebral protection with RIPoC is compelling, RIPoC-mediated neuroprotection against transient cerebral ischemic insult is still mired in controversy. In this study, we examined the effect of RIPoC induced by sublathal transient hind limb ischemia on neuronal death in the hippocampus following 5 min of transient cerebral ischemia in gerbils. Animals were randomly assigned to sham-, ischemia-, sham plus (+) RIPoC- and ischemia+RIPoC-groups. RIPoC was induced by three cycles of 5-min and 10-min occlusion-reperfusion of both femoral arteries at predetermined points in time (0, 1, 3, 6, 12 and 24h after transient cerebral ischemia). CV staining, F-J B histofluorescence staining and NeuN immunohistochemistry were carried out to examine neuroprotection in the RIPoC-mediated hippocampus 5 days after ischemia-reperfusion. In the ischemia-group, we found a significant loss of pyramidal cells in the stratum pyramidale (SP) of the hippocampal CA1 region at 5 days post-ischemia compared with the sham-group. In all of the ischemia+RIPoC-groups, the loss of pyramidal cells in the CA1 region at 5 days post-ischemia was not different from that in the ischemia-group. Our present findings indicate that RIPoC does not prevent hippocampal CA1 pyramidal cells from neuronal death induced by transient cerebral ischemia. PMID:26454372

  11. Monocarboxylate transporter 4 plays a significant role in the neuroprotective mechanism of ischemic preconditioning in transient cerebral ischemia

    PubMed Central

    Hong, Seongkweon; Ahn, Ji Yun; Cho, Geum-Sil; Kim, In Hye; Cho, Jeong Hwi; Ahn, Ji Hyeon; Park, Joon Ha; Won, Moo-Ho; Chen, Bai Hui; Shin, Bich-Na; Tae, Hyun-Jin; Park, Seung Min; Cho, Jun Hwi; Choi, Soo Young; Lee, Jae-Chul

    2015-01-01

    Monocarboxylate transporters (MCTs), which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ischemic preconditioning (IPC) on MCT4 immunoreactivity after 5 minutes of transient cerebral ischemia in the gerbil. Animals were randomly designated to four groups (sham-operated group, ischemia only group, IPC + sham-operated group and IPC + ischemia group). A serious loss of neuron was found in the stratum pyramidale of the hippocampal CA1 region (CA1), not CA2/3, of the ischemia-only group at 5 days post-ischemia; however, in the IPC + ischemia groups, neurons in the stratum pyramidale of the CA1 were well protected. Weak MCT4 immunoreactivity was found in the stratum pyramidale of the CA1 in the sham-operated group. MCT4 immunoreactivity in the stratum pyramidale began to decrease at 2 days post-ischemia and was hardly detected at 5 days post-ischemia; at this time point, MCT4 immunoreactivity was newly expressed in astrocytes. In the IPC + sham-operated group, MCT4 immunoreactivity in the stratum pyramidale of the CA1 was increased compared with the sham-operated group, and, in the IPC + ischemia group, MCT4 immunoreactivity was also increased in the stratum pyramidale compared with the ischemia only group. Briefly, present findings show that IPC apparently protected CA1 pyramidal neurons and increased or maintained MCT4 expression in the stratum pyramidale of the CA1 after transient cerebral ischemia. Our findings suggest that MCT4 appears to play a significant role in the neuroprotective mechanism of IPC in the gerbil with transient cerebral ischemia. PMID:26692857

  12. 3-N-butylphthalide improves neuronal morphology after chronic cerebral ischemia.

    PubMed

    Zhao, Wanhong; Luo, Chao; Wang, Jue; Gong, Jian; Li, Bin; Gong, Yingxia; Wang, Jun; Wang, Hanqin

    2014-04-01

    3-N-butylphthalide is an effective drug for acute ischemic stroke. However, its effects on chronic cerebral ischemia-induced neuronal injury remain poorly understood. Therefore, this study ligated bilateral carotid arteries in 15-month-old rats to simulate chronic cerebral ischemia in aged humans. Aged rats were then intragastrically administered 3-n-butylphthalide. 3-N-butylphthalide administration improved the neuronal morphology in the cerebral cortex and hippocampus of rats with chronic cerebral ischemia, increased choline acetyltransferase activity, and decreased malondialdehyde and amyloid beta levels, and greatly improved cognitive function. These findings suggest that 3-n-butylphthalide alleviates oxidative stress caused by chronic cerebral ischemia, improves cholinergic function, and inhibits amyloid beta accumulation, thereby improving cerebral neuronal injury and cognitive deficits. PMID:25206879

  13. Netrin-1 improves spatial memory and synaptic plasticity impairment following global ischemia in the rat.

    PubMed

    Bayat, Mahnaz; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Goshadrou, Fatemeh; Ronaghi, Abdolaziz; Mehdizadeh, Mehdi

    2012-05-01

    Cerebral ischemia, which is the second and most common cause of mortality, affects millions of individuals worldwide. The present study was performed to investigate whether intrahippocampal administration of netrin-1 could improve spatial memory impairment in radial arm maze task and restore long-term potentiation (LTP) in 4-vessel occlusion model of global ischemia. The results showed that intrahippocampal infusion of nerin-1 24 h after ischemia (at both doses of 400 and 800 ng) significantly ameliorated spatial memory impairment and at a dose of 800 ng was capable to improve synaptic dysfunction as observed by recovery of population spike component of basal evoked potential and LTP through enhancement of excitability and normalization of paired pulse response. Taken together, the present study shows that netrin-1 dose-dependently ameliorates spatial memory impairment and improves synaptic dysfunction as observed by recovery of population spike component of basal evoked potential and LTP in rats with global ischemia. PMID:22459051

  14. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis

    SciTech Connect

    Mayberg, M.R.; Eskridge, J.; Winn, H.R.; Eskridge, J. ); Wilson, S.E. ); Yatsu, F. ); Weiss, D.G. ); Messina, L. ); Hershey, L.A. ); Colling, C. ); Deykin, D. )

    1991-12-18

    The objective of this study was to determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant ipsilateral internal carotid artery stenosis. The study group was comprised of men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5,000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.

  15. Effects of Semelil (ANGIPARS™) on focal cerebral ischemia in male rats

    PubMed Central

    Asadi-Shekaari, M; Eftekhar Vaghefi, H; Talakoub, A; Khorram Khorshid, HR

    2010-01-01

    Background and the purpose of the study Cerebral ischemia is one of the main causes of long term disability and death in aged populations. Many herbal drugs and extracts have been used for the treatment of cerebral ischemia induced insults. This study was designed to investigate the protective effect of Semelil (ANGIPARS™), a new herbal drug, on focal cerebral ischemia in male rats. Material and methods Male rats were divided into five groups: sham-operated, ischemic animals treated with distilled water as vehicle, ischemic animals treated with 1, 10 and 100 mg/kg of Semilil respectively. Middle cerebral artery occlusion (MCAO) model was used in NMRI rats and neuronal injury analyzed in hippocampal CA1 sector after 48 hrs of Middle Cerebral Artery (MCAO). Results Results of this study showed that treatment with semelil attenuated ischemic damages and has positive effects on focal cerebral ischemia. PMID:22615626

  16. Evidence of a heterogeneous tissue oxygenation: renal ischemia/reperfusion injury in a large animal model

    NASA Astrophysics Data System (ADS)

    Crane, Nicole J.; Huffman, Scott W.; Alemozaffar, Mehrdad; Gage, Frederick A.; Levin, Ira W.; Elster, Eric A.

    2013-03-01

    Renal ischemia that occurs intraoperatively during procedures requiring clamping of the renal artery (such as renal procurement for transplantation and partial nephrectomy for renal cancer) is known to have a significant impact on the viability of that kidney. To better understand the dynamics of intraoperative renal ischemia and recovery of renal oxygenation during reperfusion, a visible reflectance imaging system (VRIS) was developed to measure renal oxygenation during renal artery clamping in both cooled and warm porcine kidneys. For all kidneys, normothermic and hypothermic, visible reflectance imaging demonstrated a spatially distinct decrease in the relative oxy-hemoglobin concentration (%HbO2) of the superior pole of the kidney compared to the middle or inferior pole. Mean relative oxy-hemoglobin concentrations decrease more significantly during ischemia for normothermic kidneys compared to hypothermic kidneys. VRIS may be broadly applicable to provide an indicator of organ ischemia during open and laparoscopic procedures.

  17. Atypical Presentation of Ocular Toxoplasmosis: A Case Report of Exudative Retinal Detachment and Choroidal Ischemia

    PubMed Central

    Al-Zahrani, Yahya A.; Al-Dhibi, Hassan A.; Al-Abdullah, Abdulelah A.

    2016-01-01

    A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid. PMID:26957857

  18. Atypical Presentation of Ocular Toxoplasmosis: A Case Report of Exudative Retinal Detachment and Choroidal Ischemia.

    PubMed

    Al-Zahrani, Yahya A; Al-Dhibi, Hassan A; Al-Abdullah, Abdulelah A

    2016-01-01

    A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid. PMID:26957857

  19. [Volume regulated anion channel and ischemia/reperfusion injury of myocardium].

    PubMed

    Li, Ping; Sun, Xiaoli

    2008-08-01

    It has been shown that a lot of diseases were related with the change or loss of Cl- channel functions. Among the Cl- channels, volume-regulated anion channel (VRAC) plays important roles in myocardial ischemia/reperfusion injury, cardiac arrhythmia and apoptosis; it may become a new target in the clinical treatment of heart diseases. This paper presents an overview of the physiological characteristics of VRAC and its relations with myocardial ischemia/reperfusion injury. PMID:18788323

  20. [Effect of phenibut and its composition with nicotinic acid on hemostasis in rats with brain ischemia].

    PubMed

    Tiurenkov, I N; Volotova, E V; Kurkin, D V; Litvinov, A A; Tarasov, A S

    2012-01-01

    It is shown that, in rats with global cerebral ischemia modeled by a complete irreversible occlusion of the common carotid artery and forced hypotension, the hemostasis is characterized by a shift toward hypercoagulation. A single preventive introduction of phenibut and, to a greater degree, a composition of phenibut with nicotinic acid, in rats with acute cerebral ischemia reduced the extent of disturbances in the hemostasis system of experimental animals. PMID:22702103

  1. Neuroprotective Effects of Quetiapine on Neuronal Apoptosis Following Experimental Transient Focal Cerebral Ischemia in Rats

    PubMed Central

    Tönge, Mehmet; Emmez, Hakan; Kaymaz, Figen; Kaymaz, Memduh

    2013-01-01

    Objective This study was undertaken in the belief that the atypical antipsychotic drug quetiapine could prevent apoptosis in the penumbra region following ischemia, taking into account findings that show 5-hydroxytryptamine-2 receptor blockers can prevent apoptosis. Methods We created 5 groups, each containing 6 animals. Nothing was done on the K-I group used for comparisons with the other groups to make sure adequate ischemia had been achieved. The K-II group was sacrificed on the 1st day after transient focal cerebral ischemia and the K-III group on the 3rd day. The D-I group was administered quetiapine following ischemia and sacrificed on the 1st day while the D-II group was administered quetiapine every day following the ischemia and sacrificed on the 3rd day. The samples were stained with the immunochemical TUNEL method and the number of apoptotic cells were counted. Results There was a significant difference between the first and third day control groups (K-II/K-III : p=0.004) and this indicates that apoptotic cell death increases with time. This increase was not encountered in the drug groups (D-I/D-II : p=1.00). Statistical analysis of immunohistochemical data revealed that quetiapine decreased the apoptotic cell death that normally increased with time. Conclusion Quetiapine is already in clinical use and is a safe drug, in contrast to many substances that are used to prevent ischemia and are not normally used clinically. Our results and the literature data indicate that quetiapine could help both as a neuronal protector and to resolve neuropsychiatric problems caused by the ischemia in cerebral ischemia cases. PMID:24044072

  2. Differential changes in phospholipase D and phosphatidate phosphohydrolase activities in ischemia-reperfusion of rat heart.

    PubMed

    Asemu, Girma; Dent, Melissa R; Singal, Tushi; Dhalla, Naranjan S; Tappia, Paramjit S

    20