Dissertations / Theses on the topic 'Thrombophlebitis'

Background: Many risk factors for venous thromboembolism have been identified, but two particular exposures - the use of combined oral contraceptives and long-distance air travel - have generated considerable concern in recent years. In contrast, a possible link between venous thromboembolism and a third exposure - the use of psychotropic drugs - was first raised in the 1950s, but has received surprisingly little attention. Information about all three exposures and the risk of fatal events is limited. These risks were examined in three inter-related national population-based studies. Methods: The underlying study population included all men and women aged 15 - 59 years who died in New Zealand between 1990 and 2000, for whom the underlying cause of death was pulmonary embolism. The potential associations between fatal pulmonary embolism and the use of oral contraceptives and psychotropic drugs were explored in a general practice records-based case-control study. Non-users were the reference category for all analyses. Contraceptive supply data were used to estimate the absolute risk of death from pulmonary embolism in users of oral contraceptives. A second case-control study, in which computer-assisted telephone interviews were undertaken with the next of kin of cases who had been resident in New Zealand, and with sex and age-matched controls randomly selected from the electoral roll, investigated the possible association between long-distance air travel and fatal pulmonary embolism. Finally, the absolute risk of dying from pulmonary embolism following a long-distance flight was estimated in a descriptive study based on official migration data and deaths in recent air travellers. Results: The adjusted odds ratio for use of any oral contraceptive in the three months before the index date (the onset of the fatal episode) was 13.1 (95% CI 4.4 - 39.0). The odds ratio for formulations containing desogestrel and gestodene was about three times higher than the point estimate for levonorgestrel products; preparations containing cyproterone acetate appeared to carry the highest risk. The estimated absolute risk of fatal pulmonary embolism in current users of oral contraceptives was 10.5 (95% CI 6.2 - 16.6) per million woman-years. The adjusted odds ratio for current use of any antipsychotic was 13.3 (95% CI 2.3 - 76.3). Low-potency antipsychotics carried a 20-fold increase in risk; thioridazine was the main drug involved. Antidepressant use was also associated with a significantly increased risk (adjusted odds ratio 4.9 [95% CI 1.1 - 22.5]). Compared with non-travellers, people who had undertaken a flight of more than eight hours� duration in the preceding four weeks were eight times more likely to die from pulmonary embolism (odds ratio 7.9 [95% CI 1.1 - 55.1]). The absolute risk of fatal pulmonary embolism following air travel of more than eight hours was 1.3 (95% CI 0.4 - 3.0) per million arrivals. Conclusions: The present research was the first to have estimated the relative risks of fatal pulmonary embolism in relation to three exposures: oral contraceptive use in a population in which preparations containing desogestrel and gestodene preparations were widely used, conventional antipsychotics, and long-distance air travel. The findings were consistent with previous, and subsequent, studies of non-fatal events. Increased risks of fatal pulmonary embolism in users of antidepressants, and in people with an intellectual disability, have not been described previously and warrant further investigation. Referral and diagnostic biases are very unlikely in these studies of fatal events, and other types of bias and possible confounding are considered unlikely explanations for the findings.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are together known as venous thrombo-embolism (VTE), one of the most common complications after surgery and trauma injury. In the case of critically ill patients, it is also a significant medical and financial burden, associated with high mortality and morbidity. In recent years, much evidence has come to light showing that DVT prophylaxis can effectively reduce DVT, and it has been incorporated into various evidenced-based guidelines (Geerts et al., 2008; Nicolaides et al., 2006). The objectives of this study are to examine, through a comprehensive literature review of published studies, the effectiveness of various means of DVT prophylaxis aimed at reducing DVT, and to develop an evidence-based guideline for the use of DVT prophylaxis in surgical intensive care unit (ICU) settings. Keywords related to DVT prophylaxis were used in conducting the search in electronic bibliographic databases like MEDLlNE, CINAHL, PubMed and the Cochrane Library. A total of 110 articles were identified, and seven studies fulfilled the inclusion criteria of the study. Data from the seven studies have been extracted to form tables of evidence; the qualities of the studies were then rated, and the levels of evidence assigned according to SIGN 50: A guideline developer’s handbook (Network, Harbour & Forsyth, 2011). Three studies attained a higher level of evidence with strong methodological design and demonstrated a statistically significant reduction in the incidence of DVT. The implementation potential of DVT prophylaxis was examined in terms of target setting, target audience, transferability of findings, feasibility and cost-benefit ratio. And it was found that the development of evidence-based guidelines for DVT prophylaxis was feasible, cost-beneficial and transferable in current settings. The findings of the seven reviewed studies have been translated into an evidence-based DVT prophylaxis guideline. The main focuses of the guideline are the choice of prophylaxis used with surgical ICU patients and the strategies for improving adherence and prophylaxis monitoring. Combined pharmacological and mechanical DVT prophylaxis is recommended for ICU patients who are at high risk of DVT. For patients with active bleeding or high risk of bleeding, mechanical prophylaxis like intermittent pneumatic compressor (IPC) or gradual compression stocking (GCS) should be used first, followed by a review for pharmacological prophylaxis when the risk of bleeding has decreased. In addition, routine assessment of thrombosis and bleeding risk for high-risk ICU patients and regular checking of fitting and functioning of the DVT prophylaxis are recommended. An implementation plan consisting of communication, pilot and evaluation plan was developed. A 12-month programme including communication with stakeholders, marketing of the innovation, training of frontline staff, a five-week pilot study and implementation of the guideline followed by evaluation will be carried out. In the evaluation, programme effectiveness was assessed in terms of patient outcome (e.g. incidence of DVT), process outcomes (e.g. level of knowledge related to DVT, compliance with the guideline and level of staff satisfaction) and system outcome (e.g. financial cost reduction).
published_or_final_version
Nursing Studies
Master
Master of Nursing

Background. Peripheral vein infusion thrombophlebitis (PVIT) is a complication of intravenous therapy. We hypothesized that inherited thrombophilia may increase the risk of PVIT.
Purpose. In preparation for a multi-center study of our hypothesis, we conducted a pilot study to estimate PVIT incidence, measure the prevalence of inherited thrombophilia, and pilot test the study procedures.
Methods. A prospective case-control study of 25 cases (patients with PVIT) matched on catheter duration to 25 controls. PVIT risk factors and inherited thrombophilia were assessed.
Results. PVIT incidence was 14 per 1000 catheter-days. There were no significant differences in the prevalence of the inherited thrombophilia disorders among cases and controls (32% vs. 48%). A previous history of PVIT was noted in 4 cases compared to 0 controls. Procedural problems included a high rate of non-consent and inadequate communication with the laboratory.
Conclusions. Though an association between PVIT and inherited thrombophilia was not shown, a previous history of PVIT among cases supports a biological predisposition to PVIT. Our pilot study did provide useful data on PVIT incidence and procedural issues used to design a more definitive study of inherited thrombophilia and PVIT.

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Foi realizada a avaliação morfológica e morfométrica da veia cefálica submetida à pinçamento de cinco equinos hígidos. Foram testadas as pinças hemostáticas: Diffenbach bulldog, De Bakey bulldog, Rochester reta e De Bakey com cremalheira. Após 15 minutos da aplicação das referidas pinças, foi realizada a flebectomia parcial e coletadas as amostras referentes a cada segmento do vaso pinçado e do segmento controle sem pinçamento. Das peças procedeu-se as preparações histológicas dos segmentos da veia nas colorações de Hematoxilina-Eosina e Tricrômio de Masson, os cortes histológicos foram avaliados por microscopia óptica. Foi realizada análise morfológica das veias, de forma qualitativa, utilizando para isto uma escala de avaliação de lesões vasculares após pinçamento; a avaliação morfométrica, quantificando em micrometros o achatamento produzido pelas pinças nas diferentes camadas vasculares. Em ambos os estudos, morfológico e morfométrico, as pinças com serrilhamento transversal e fechamento tipo cremalheira causaram as maiores alterações, observou se marcada vacuolização das células musculares e desarranjo na túnica media com perda marcada das células endoteliais da túnica intima do vaso estudado.
Morphometric and morphologic evaluation of the cephalic vein of five healthy horses submitted to clamping was done. Hemostatic clamps tested were Dieffenbach bulldog, De Bakey bulldog, Rochester straight and De Bakey with ratchets. 15 minutes after mentioned clamps were applied partial phlebotomy was performed and histologic sections of the veins were prepared and stained with Hematoxylin-Eosin and Masson Trichrome, after the stained preparations were evaluated by light microscopy. A qualitative morphological analysis of the veins was performed using a rating scale of vascular lesions after clamping; the morphometric evaluation consisted in quantifying in micrometers the flattening produced by the hemostatic clamps in the different vascular beds. In both studies, morphologic and morphometric, hemostats with transverse serration and ratcheted mechanism caused major changes, pronounced vacuolization of the muscle cells, derangement of the medium tunic and marked loss of endothelial cells of the intima tunic was observed in the vessel studied.

Orientador: Carlos Alberto Hussni
Resumo: A trombose de jugular é problema freqüente na medicina eqüina, implicando muitas vezes em conseqüências fatais. O diagnóstico é relativamente simples, baseado nos achados físicos, nas imagens angiográficas e ultra-sonográficas. A terapêutica conservativa empregada em grande parte dos casos é insatisfatória. O objetivo deste trabalho foi avaliar em eqüinos a aplicabilidade da trombectomia com cateter de fogarty, técnica esta rotineiramente empregada pela medicina humana, no restabelecimento da perviedade vascular. Foram utilizados 10 eqüinos divididos em 2 grupos, com cinco animais cada, em que se induziu a trombose de jugular unilateral direita, através do acesso cirúrgico à veia e aplicação de sutura estenosante e injeção de glicose a 50%. No grupo controle avaliou-se a evolução da tromboflebite sem qualquer tipo de intervenção terapêutica. Os animais do grupo tratado foram submetidos a trombectomia com cateter de Fogarty. Foram avaliados os parâmetros físicos gerais, regionais, ultra-sonográficos e angiográficos contrastados, nos momentos pré-indução (MPRÉ), indução da trombose (MTI) e dez dias de evolução da trombose (M13). A técnica empregada induziu a tromboflebite, que obstruiu completamente um segmento da veia jugular de todos os animais. Os animais do grupo controle mantiveram os trombos obstruindo totalmente o lume vascular até o final do período de avaliação, sendo que avaliações regionais mostraram principalmente o edema parotídeo e o ingurgitamento vascular, cranial a tromboflebite de jugular. Nos exames ultra-sonográficos e angiográficos, o grupo tratado apresentou todas as veias pérvias ao final do experimento, com remissão total dos sinais clínicos. Concluiu-se que a técnica da trombectomia com cateter de Fogarty foi eficiente na desobstrução da veia jugular submetida à trombose experimental.
Abstract: Thrombosis of jugular vein is a frequent problem in the equine medicine, implying many times in fatal consequences. The diagnosis is relatively simple, based in the clinical findings, angiographics images and ultrasonographycs. The therapeutic employed to a large extent of the cases is unsatisfactory. The objective of this work was to evaluate in horses the applicability of the thrombectomy with Fogarty catheter, technique routinely used in medicine, in the reestablishment of the perviousness vascular. 10 horse divided in 2 groups had been used, with five animals each, and induced thrombosis of right unilateral jugular vein, through the surgical access to the vein and application of stenotic suture and glucose 50% injection. In the controlled group it was evaluated evolution of the thrombophlebitis without any type of therapeutical intervention. The animals of the treatead group had been submitted to the thrombectomy with Fogarty catheter. General clinical parameters were analysed at the moment of the preinduction (MPRÉ), induction of thrombosis (MTI), and ten days of evolution of thrombosis (M10). The employed technique induced the thrombophlebitis that completely obstructed a segment of the jugular vein in all the animals. The animals of the control group had kept the thrombus totally obstructing the vascular lumen until the end of the period of evaluation, being that regional evaluations had mainly shown parotid edema and the vascular dilated, cranial the thrombophlebitis of jugular vein. The treated group presented all the pervious veins to the end of the experiment, confirmed by angiographics and ultrasonographics examinations, with total remission of the clinical sign. So far, it was concluded that the technique of the thrombectomy with catheter of Fogarty was efficient in eliminating the obstruction of the jugular vein submitted to experimental thrombosis.
Doutor

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Universidade Estadual Paulista (UNESP)
A trombose de jugular é problema freqüente na medicina eqüina, implicando muitas vezes em conseqüências fatais. O diagnóstico é relativamente simples, baseado nos achados físicos, nas imagens angiográficas e ultra-sonográficas. A terapêutica conservativa empregada em grande parte dos casos é insatisfatória. O objetivo deste trabalho foi avaliar em eqüinos a aplicabilidade da trombectomia com cateter de fogarty, técnica esta rotineiramente empregada pela medicina humana, no restabelecimento da perviedade vascular. Foram utilizados 10 eqüinos divididos em 2 grupos, com cinco animais cada, em que se induziu a trombose de jugular unilateral direita, através do acesso cirúrgico à veia e aplicação de sutura estenosante e injeção de glicose a 50%. No grupo controle avaliou-se a evolução da tromboflebite sem qualquer tipo de intervenção terapêutica. Os animais do grupo tratado foram submetidos a trombectomia com cateter de Fogarty. Foram avaliados os parâmetros físicos gerais, regionais, ultra-sonográficos e angiográficos contrastados, nos momentos pré-indução (MPRÉ), indução da trombose (MTI) e dez dias de evolução da trombose (M13). A técnica empregada induziu a tromboflebite, que obstruiu completamente um segmento da veia jugular de todos os animais. Os animais do grupo controle mantiveram os trombos obstruindo totalmente o lume vascular até o final do período de avaliação, sendo que avaliações regionais mostraram principalmente o edema parotídeo e o ingurgitamento vascular, cranial a tromboflebite de jugular. Nos exames ultra-sonográficos e angiográficos, o grupo tratado apresentou todas as veias pérvias ao final do experimento, com remissão total dos sinais clínicos. Concluiu-se que a técnica da trombectomia com cateter de Fogarty foi eficiente na desobstrução da veia jugular submetida à trombose experimental.
Thrombosis of jugular vein is a frequent problem in the equine medicine, implying many times in fatal consequences. The diagnosis is relatively simple, based in the clinical findings, angiographics images and ultrasonographycs. The therapeutic employed to a large extent of the cases is unsatisfactory. The objective of this work was to evaluate in horses the applicability of the thrombectomy with Fogarty catheter, technique routinely used in medicine, in the reestablishment of the perviousness vascular. 10 horse divided in 2 groups had been used, with five animals each, and induced thrombosis of right unilateral jugular vein, through the surgical access to the vein and application of stenotic suture and glucose 50% injection. In the controlled group it was evaluated evolution of the thrombophlebitis without any type of therapeutical intervention. The animals of the treatead group had been submitted to the thrombectomy with Fogarty catheter. General clinical parameters were analysed at the moment of the preinduction (MPRÉ), induction of thrombosis (MTI), and ten days of evolution of thrombosis (M10). The employed technique induced the thrombophlebitis that completely obstructed a segment of the jugular vein in all the animals. The animals of the control group had kept the thrombus totally obstructing the vascular lumen until the end of the period of evaluation, being that regional evaluations had mainly shown parotid edema and the vascular dilated, cranial the thrombophlebitis of jugular vein. The treated group presented all the pervious veins to the end of the experiment, confirmed by angiographics and ultrasonographics examinations, with total remission of the clinical sign. So far, it was concluded that the technique of the thrombectomy with catheter of Fogarty was efficient in eliminating the obstruction of the jugular vein submitted to experimental thrombosis.

Bakgrund: Ungefär hälften av alla vuxna som vårdas på sjukhus erhåller en perifer venkateter (PVK) för intravenöst behandling. Det finns risk för lindriga eller allvarliga komplikationer. Den vanligaste komplikationen är tromboflebit och den allvarligast är infektion. I Sverige är det sjuksköterskan som ansvarar för insättning, skötsel, borttagande och dokumentation av PVK. Omvårdnaden vid handhavande av PVK är eftersatt och sjuksköterskan bör förvissa sig om att deras kunskaper är uppdaterad och evidensbaserad för att minska risken för komplikationer. Syfte: Studiens syfte var att beskriva faktorer av betydelse som kan förebygga PVK relaterade komplikationer med fokus på tromboflebit och infektion. Metod: En litteraturstudie som är baserad på 15 artiklar, 2009-2014. Resultat: Faktorer av betydelse för att förebygga tromboflebit och infektion i samband med PVK är inläggningsteknik, anatomisk placering, PVK storlek, slutna- eller öppna system och hur länge en PVK är in situ. Utbildning av personalen och feedback förbättrade handhavandet av PVK och följsamheten till riktlinjer. Slutsats: Flera faktorer påverkar om patienten utvecklar tromboflebit eller infektion i samband med PVK. Flera går att förebygga genom att följsamheten till riktlinjer förbättras och utförda omvårdnadsåtgärder dokumenteras.
Background:About half of all adults who are being cared for in hospital receivea peripheral venous catheter (PVC) for intravenous treatment. There is a risk of mild or serious complications. The most common complication is thrombophlebitis and the most serious is infection. In Sweden it isthe nurse who is responsible for the insertion, management, removal and documentation of PVC. Nursing care in PVCis neglected and the nurse should ensure that their knowledge is up-to-date and evidence-based in order to reduce the risk of complications.Aim:The aim of the studywas to describe factors that can prevent PVCrelated complications with focus on thrombophlebitis and infection.Method:Aliterature review based on 15articles, 2009-2014. Results:Factors of importance to prevent thrombophlebitis and infection associated with the PVCis insertion technique, anatomic location, PVCsize, closed or open system and how long PVCis in situ. Staff training and feedback improved management of PVCand adherence to guidelines. Conclusion:Several factors affect if the patient developsfrom thrombophlebitis or infection associated with PVC. Many are preventable by adherence to the guidelines be improved and performed nursing interventions should be documented.

Venous thromboembolism (VTE), comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a common and preventable cause of morbidity among individuals and hospital in-patient mortality. Further, it imposes a substantial burden upon the community and its health care system and economy. Studies performed in Western societies suggest that the annual incidence of DVT is about 0.8 to 1.2 per 1,000, PE about 0.3 to 0.6 per 1,000, and VTE about 1.0 to 1.8 per 1,000. However, it is not known if these estimates can be generalised to the Australian population because of differences in ethnic composition and other risk factors for VTE among the different populations. In this thesis, I undertook a prospective, community-based cohort study over a 13-month period in 2003 – 2004 to determine the incidence and crude event rate of symptomatic, objectively verified VTE in north-east metropolitan Perth. The study population was broadly representative of the national Australian population in terms of age, sex and ethnic distribution. Cases were identified through multiple overlapping sources. The incidence of DVT, PE and VTE in the community were 0.52 (95% confidence interval, CI: 0.41 – 0.63), 0.31 (95% CI: 0.22 – 0.40) and 0.83 (95% CI: 0.69 – 0.97) per 1000 per year, respectively. The annual incidence of DVT, adjusted to the World Standard population, was 0.35 (95% CI: 0.26 – 0.44) per 1000, PE 0.21 (95% CI: 0.14 – 0.28) per 1000 and VTE 0.57 (95% CI: 0.47 – 0.67) per 1000. The crude event rate for VTE was 0.85 (95% CI: 0.71 – 0.99) per 1000 per year. These findings suggest that the incidence of DVT, PE and VTE are lower than in other Western societies studied. Possible reasons include a lower prevalence of exposure to causal risk factors (genetic and environmental) and incomplete case ascertainment. Knowledge of the local incidence and event rate allows health planners to allocate appropriate resources and evaluate cost-effective preventive measures.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
A tromboflebite jugular é frequentemente encontrada em equinos causando comprometimento circulatório grave nas regiões cervical e cefálica. Até o presente momento, não há relatos que avaliem as alterações hemodinâmicas em equinos causadas pela obstrução venosa jugular por trombo durante o exercício. Da mesma forma, não há relatos da eficácia da terapia trombolítica regional com estreptoquinase no tratamento desta alteração vascular em equinos. Os objetivos deste trabalho foram: avaliação da técnica cirúrgica de canulação da artéria facial e manutenção prolongada do cateter com solução de heparina e ácido ascórbico, visando realizar de forma seriada colheita de amostras sanguíneas e avaliação invasiva de pressão arterial, durante o exercício em esteira rolante; estabelecimento de um modelo de indução de tromboflebite da veia jugular de equinos utilizando solução de dois agentes esclerosantes associados: oleato de etanolamina 5% e glicose 50%; avaliação da terapia trombolítica regional com estreptoquinase como tratamento da tromboflebite jugular induzida experimentalmente em equinos; avaliação hemodinâmica de equinos submetidos a oclusão unilateral da veia jugular por tromboflebite induzida. Vinte equinos adultos foram utilizados para conclusão dos protocolos. O procedimento de cateterização da artéria facial e manutenção do cateter com solução de heparina e ácido ascórbico, manteve a via arterial viável por 25 dias. O protocolo de indução não cirúrgica de tromboflebite jugular experimental foi eficaz em reproduzir a lesão de forma padronizada. Foram observadas alterações hemodinâmicas significativas nos equinos apresentando oclusão jugular por trombose induzida, durante o exercício de esforço progressivo em esteira rolante...
Thrombophlebitis of the jugular vein is commonly observed in horses leading to head and neck circulatory impairment. To date, there are no reports evaluating hemodynamic changes in horses presenting thrombus obstruction during the exercise. In addition, there are no studies about the use of streptokinase in thrombolytic therapy for treatment of jugular vein thrombophlebitis in horses. The purposes of this study were: to evaluate the technique for facial artery catheter implantation and long-term maintenance using heparin and ascorbic acid as a filling solution, to perform serial blood sampling and invasive arterial pressure measurement during the exercise on treadmill; establishment of an equine jugular vein thrombophlebitis induction model using a solution of two sclerosing agents in association: ethanolamine oleate 5% and glucose 50%; hemodynamic evalution in horses presenting unilateral occlusion of the jugular vein through experimental inducted thrombophlebitis; evaluation of regional thrombolytic therapy using streptokinase as a treatment for jugular vein inducted thrombophlebitis in horses. Twenty adult horses were assessed to conclude all the protocols. Procedures for facial artery catheterization and maintenance using heparin and ascorbic acid as a filling solution kept the arterial line open for 25 days. The nonsurgical protocol to induce experimental jugular thrombophlebitis was efficient in reproduce a standardized lesion. Significative hemodynamic changes were observed in the horses presenting jugular occlusion through induced thrombosis during the exercise on treadmill. Streptokinase thrombolytic therapy test showed that the drug exerts fibrinolytic action on horses’ thrombus, however it was not capable to permanently recanalize injuried vessels

Orientador: José Corrêa de Lacerda Neto
Banca: Julio Carlos Canola
Banca: Áureo Evangelista Santana
Banca: Olivier Lepage
Banca: Juliana Regina Peiró
Resumo: A tromboflebite jugular é frequentemente encontrada em equinos causando comprometimento circulatório grave nas regiões cervical e cefálica. Até o presente momento, não há relatos que avaliem as alterações hemodinâmicas em equinos causadas pela obstrução venosa jugular por trombo durante o exercício. Da mesma forma, não há relatos da eficácia da terapia trombolítica regional com estreptoquinase no tratamento desta alteração vascular em equinos. Os objetivos deste trabalho foram: avaliação da técnica cirúrgica de canulação da artéria facial e manutenção prolongada do cateter com solução de heparina e ácido ascórbico, visando realizar de forma seriada colheita de amostras sanguíneas e avaliação invasiva de pressão arterial, durante o exercício em esteira rolante; estabelecimento de um modelo de indução de tromboflebite da veia jugular de equinos utilizando solução de dois agentes esclerosantes associados: oleato de etanolamina 5% e glicose 50%; avaliação da terapia trombolítica regional com estreptoquinase como tratamento da tromboflebite jugular induzida experimentalmente em equinos; avaliação hemodinâmica de equinos submetidos a oclusão unilateral da veia jugular por tromboflebite induzida. Vinte equinos adultos foram utilizados para conclusão dos protocolos. O procedimento de cateterização da artéria facial e manutenção do cateter com solução de heparina e ácido ascórbico, manteve a via arterial viável por 25 dias. O protocolo de indução não cirúrgica de tromboflebite jugular experimental foi eficaz em reproduzir a lesão de forma padronizada. Foram observadas alterações hemodinâmicas significativas nos equinos apresentando oclusão jugular por trombose induzida, durante o exercício de esforço progressivo em esteira rolante ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Thrombophlebitis of the jugular vein is commonly observed in horses leading to head and neck circulatory impairment. To date, there are no reports evaluating hemodynamic changes in horses presenting thrombus obstruction during the exercise. In addition, there are no studies about the use of streptokinase in thrombolytic therapy for treatment of jugular vein thrombophlebitis in horses. The purposes of this study were: to evaluate the technique for facial artery catheter implantation and long-term maintenance using heparin and ascorbic acid as a filling solution, to perform serial blood sampling and invasive arterial pressure measurement during the exercise on treadmill; establishment of an equine jugular vein thrombophlebitis induction model using a solution of two sclerosing agents in association: ethanolamine oleate 5% and glucose 50%; hemodynamic evalution in horses presenting unilateral occlusion of the jugular vein through experimental inducted thrombophlebitis; evaluation of regional thrombolytic therapy using streptokinase as a treatment for jugular vein inducted thrombophlebitis in horses. Twenty adult horses were assessed to conclude all the protocols. Procedures for facial artery catheterization and maintenance using heparin and ascorbic acid as a filling solution kept the arterial line open for 25 days. The nonsurgical protocol to induce experimental jugular thrombophlebitis was efficient in reproduce a standardized lesion. Significative hemodynamic changes were observed in the horses presenting jugular occlusion through induced thrombosis during the exercise on treadmill. Streptokinase thrombolytic therapy test showed that the drug exerts fibrinolytic action on horses' thrombus, however it was not capable to permanently recanalize injuried vessels
Doutor

冠狀動脈旁路移植術是治療合併左主幹及多隻冠狀動脈狹窄性病變患者的理想方法。然而靜脈橋失效極大地限制了冠脈搭橋手術的遠期療效。基於對靜脈橋失效潛在機制的研究，近年來開發出了多種針對性的防治手段。但是除了積極的降脂治療，目前尚未有其它療法獲得臨床證實可以有效改善靜脈橋遠期通暢率。所以，本研究旨在探索與防治靜脈橋再狹窄相關的新型生物標靶和防治策略。
我們應用豬大隱靜脈植入頸內動脈模型，觀察骨橋蛋白是否參與靜脈橋動脈化進程以及其與基質金屬蛋白酶功能活動的關係。我們發現骨橋蛋白表達在靜脈橋動脈化過程中顯著增加，並且與基質金屬蛋白酶2/9和增殖細胞數量的變化同步。此外，骨橋蛋白富集區域在靜脈橋內的再分佈與血管壁重構進程相關。這些結果表明, 骨橋蛋白積極參與了靜脈橋壁重構，而抑制骨橋蛋白表達作為防治靜脈橋失效的治療策略值得深入研究。
我們運用體外培養的方法研究了在高糖環境中骨成形蛋白4與靜脈內皮細胞舒張功能障礙的關係。我們發現，骨成形蛋白4在糖尿病患者的大隱靜脈與高糖培養的人臍靜脈內皮細胞中顯著增加；而骨成形蛋白4的高表達與靜脈血管內皮細胞依賴性舒張功能受損有關。本研究結果為解釋糖尿病患者有著較高的冠脈搭橋術後靜脈橋失效率提供了新證據，同時也為改善此類患者靜脈橋通暢率提出了潛在的治療靶點。
通過轉染金屬蛋白酶-3抑制物 (TIMP-3)基因來針對性地抑制血管中層平滑肌細胞的遷移和增殖，可以有效地減少靜脈橋新生內膜增生。基於前期研究，我們觀察了在豬模型中運用重組腺病毒轉載TIMP-3(RAdTIMP-3) 防治靜脈橋狹窄的遠期效果(3個月)。結果發現，即使在腺病毒載體已被清除的情況下，RAdTIMP-3對靜脈橋的良性保護作用仍持續存在。此外，我們通過比較術後7天與3個月獲取的橋血管中炎性標記物表達的差異，發現腺病毒轉染並未對靜脈橋造成長期的炎性損害。因此，我們認為RAd-TIMP3基因能夠安全有效地防治靜脈橋遠期狹窄。本研究結果為TIMP-3基因治療轉化至臨床實踐提供了可靠的前期證據。
Coronary artery bypass grafting (CABG) remains the “gold standard“ for treating high-risk patients with unprotected left-main or multi-vessel coronary lesions. However, the long-term success of CABG is largely limited by an inadequate patency of saphenous vein grafts. To date, various therapeutic strategies targeting at the underlying mechanisms involved in the pathogenesis of vein graft failure (VGF) have been proposed and tested. However, apart from lipid-lowering therapy, no other intervention appears to have sustained benefits on improving vein graft patency in the clinical setting. Therefore, the aim of this study is to explore novel sets of molecular targets and effective therapeutic strategies to prevent VGF.
Novel molecules involved in the pathogenesis of vein graft failure
Using a porcine model, we assessed the involvement of osteopontin (OPN) in the venous arterialization and its relationship with the matrix metalloproteinases (MMPs). We found that the expression of OPN was significantly increased over the 3-month study period. Moreover, the expression of OPN at different time points well correlated with the fluctuating activities of MMP-2/9 and the number of proliferative cells. We also observed a time-dependent redistribution of OPN protein accumulating in different layers of the venous wall. These findings suggest a contributory role of OPN protein involved in the process of vein graft wall remodeling.
We used pig and human saphenous veins (SVs), as well as human umbilical endothelial cells (HUVECs), to investigate the changes of bone morphogenic protein-4 (BMP4) expression and its effects on endothelium-dependent relaxations (EDRs) under hyperglycemic conditions. Our results demonstrated a marked increase of BMP4 expression in SVs from diabetic patients and in HUVECs cultured with hyperglycemic medium. Moreover, such an increase of BMP4 contributes significantly to the impaired EDRs in venous conduits. Our findings add novel evidence that helps explain the high prevalence of VGF in diabetic patients undergoing CABG, and also suggest BMP4 as a potential therapeutic target to improve vein graft patency in this population.
Novel Therapeutic Strategy -- Gene Therapy
Aiming at blocking the development of neointima formation caused by vascular smooth muscle cells migration and proliferation, genetic transfection of tissue inhibitor of metalloproteinases-3 (TIMP-3) to vein grafts has shown promising results. Based on our previous study, we used recombinant adenoviruses that carry TIMP-3 (RAdTIMP-3) as a therapeutic gene to evaluate its long-term (3 months) effects on the pathological vein graft wall thickening in vivo. We found that the RAdTIMP-3-treated vein grafts had significantly reduced intimal and medial thickness compared with grafts from the control groups at 3 months, even after adenoviruses had already been cleared from transduced tissue. Furthermore, by assessing the amount of macrophages and the level of three inflammatory biomarkers within grafts harvested at 7 days and 3 months after implantation, we did not observe any detrimental effects of adenoviral transfection on the inflammatory status within the vein grafts. We therefore concluded that overexpression of TIMP-3 could effectively inhibit vein graft wall over-thickening in the longer-term. Our findings suggested the ex vivo RAdTIMP-3 gene therapy an attractive candidate for future clinical translation.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Hu, Jia.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2012.
Includes bibliographical references (leaves 109-143).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
Abstract --- p.i
Declaration --- p.vii
Acknowledgement --- p.viii
Table of Contents --- p.x
List of Abbreviations --- p.xvi
List of Figures/Tables --- p.xviii
Chapter Chapter I --- INTRODUCTION --- p.1
Chapter 1.1 --- SAPHENOUS VEIN GRAFTS IN CORONARY REVASCULARIZATION --- p.3
Chapter 1.1.1 --- The use of venous conduits in CABG --- p.3
Chapter 1.1.2 --- The long-term patency of saphenous vein grafts --- p.4
Chapter 1.1.3 --- PCI for vein graft diseases --- p.6
Chapter 1.1.4 --- Vein graft failure and adverse clinical outcomes --- p.7
Chapter 1.2 --- MORPHOLOGY AND PHYSIOLOGY OF A NORMAL SAPHENOUS VEIN --- p.8
Chapter 1.3 --- THE PATHOPHYSIOLOGY OF VEIN GRAFT FAILURE --- p.10
Chapter 1.3.1 --- The quality of vein grafts prior to grafting --- p.10
Chapter 1.3.1.1 --- Pre-existing endothelial dysfunction --- p.10
Chapter 1.3.1.2 --- Surgical injuries --- p.11
Chapter 1.3.2 --- Mechanisms of the pathological vein graft wall thickening --- p.12
Chapter 1.3.2.1 --- Platelet activation and coagulant cascade --- p.13
Chapter 1.3.2.2 --- Leukocytes recruitment and inflammation --- p.13
Chapter 1.3.2.3 --- Hemodynamic forces --- p.14
Chapter 1.3.2.4 --- Growth factors and VSMCs activation --- p.15
Chapter 1.3.2.5 --- Contribution of adventitial and graft-extrinsic cells --- p.16
Chapter 1.3.2.6 --- Oxidative stress --- p.17
Chapter 1.3.2.7 --- Concomitant risk factors and vein graft atherosclerosis --- p.17
Chapter 1.4 --- STRATEGIES FOR THE PREVENTION OF VEIN GRAFT FAILUR --- p.18
Chapter 1.4.1 --- Minimizing surgical injuries --- p.18
Chapter 1.4.2 --- Pharmacologic interventions --- p.19
Chapter 1.4.3 --- External supports --- p.21
Chapter 1.4.4 --- Genetic engineering of the vein graft --- p.23
Chapter 1.4.4.1 --- Delivery systems --- p.23
Chapter 1.4.4.2 --- Therapeutic strategies of the genetic modulation --- p.25
Chapter 1.4.4.2.1 --- Antithrombotic and anticoagulant strategies --- p.25
Chapter 1.4.4.2.2 --- Therapies for endothelial protection and regeneration --- p.27
Chapter 1.4.4.2.3 --- Reducing inflammation and atherosclerosis --- p.28
Chapter 1.4.4.2.4 --- Antioxidative therapy --- p.29
Chapter 1.4.4.2.5 --- Therapies targeting at the cellular proliferation --- p.29
Chapter 1.4.4.2.6 --- Inhibiting extracellular matrix reorganization --- p.31
Chapter 1.5 --- CONCLUSIONS --- p.32
Chapter Chapter II --- MATERIALS AND METHODS --- p.34
Chapter 2.1 --- MATERIALS --- p.35
Chapter 2.1.1 --- Reagents and equipment --- p.35
Chapter 2.1.1.1 --- General materials and equipment for animal model --- p.35
Chapter 2.1.1.2 --- General reagents and equipment for western blot --- p.35
Chapter 2.1.1.3 --- General reagents and equipment for immunohistochemistry --- p.36
Chapter 2.1.1.4 --- General reagents and equipment for venous ECs functional studies --- p.37
Chapter 2.1.2 --- Buffers --- p.37
Chapter 2.1.2.1 --- Buffers for human and animal samples --- p.37
Chapter 2.1.2.2 --- Buffers for western blot --- p.38
Chapter 2.1.2.3 --- Immunohistochemistry buffers --- p.39
Chapter 2.1.2 --- Antibodies and adenoviral vectors --- p.41
Chapter 2.2 --- METHODS --- p.41
Chapter 2.2.1 --- Animal model --- p.41
Chapter 2.2.2 --- Functional studies --- p.44
Chapter 2.2.3 --- Human endothelial cells culture --- p.44
Chapter 2.2.4 --- Western blot analysis --- p.45
Chapter 2.2.5 --- Immunochemistry and immunofluorescence --- p.46
Chapter Chapter III --- ROLE OF BMP4 IN VENOUS ENDOTHELIAL DYSFUNCTION --- p.47
Chapter 3.1 --- INTRODUCTION --- p.48
Chapter 3.2 --- MATERIALS AND METHODS --- p.49
Chapter 3.2.1 --- Patient characteristics --- p.49
Chapter 3.2.2 --- Preparation of human vein segments --- p.51
Chapter 3.2.3 --- Porcine saphenous veins culture --- p.51
Chapter 3.2.4 --- Functional studies of vein segments --- p.52
Chapter 3.2.5 --- Cell culture --- p.53
Chapter 3.3.6 --- Western blot analysis of BMP4 --- p.53
Chapter 3.3.7 --- ROS measurement by dihydroethidium fluorescence imaging --- p.54
Chapter 3.2.8 --- Statistical analysis --- p.54
Chapter 3.3 --- RESULTS --- p.54
Chapter 3.3.1 --- ACh-induced EDRs are impaired in diabetic veins --- p.54
Chapter 3.3.2 --- The expression of BMP4 is upregulated under hyperglycemic condition --- p.55
Chapter 3.3.3 --- BMP4 induces venous endothelial dysfunction in diabetes --- p.56
Chapter 3.3.4 --- BMP4 impairs EDRs in cultured porcine saphenous veins --- p.58
Chapter 3.4 --- DISCUSSION --- p.59
Chapter 3.5 --- CONCLUSIONS --- p.62
Chapter Chapter IV --- ROLE OF OSTEOPONTIN IN VEIN GRAFT REMODELING --- p.63
Chapter 4.1 --- INTRODUCTION --- p.64
Chapter 4.2 --- MATERIALS AND METHODS --- p.66
Chapter 4.2.1 --- Surgical procedures --- p.66
Chapter 4.2.2 --- Immunohistochemistry --- p.67
Chapter 4.2.3 --- Western blot --- p.68
Chapter 4.2.4 --- Gelatin zymography --- p.69
Chapter 4.2.5 --- Cell proliferation --- p.69
Chapter 4.2.6 --- Statistical analysis --- p.69
Chapter 4.3 --- RESULTS --- p.70
Chapter 4.3.1 --- Expression and redistribution of OPN protein within the venous wall --- p.70
Chapter 4.3.2 --- The fluctuating expression of the matrix metalloproteinases --- p.72
Chapter 4.3.3 --- Vascular smooth muscle cells proliferation --- p.74
Chapter 4.4 --- DISCUSSION --- p.75
Chapter 4.5 --- CONCLUIONS --- p.79
Chapter Chapter V --- TIMP-3 GENE THERAPY FOR NEOINTIMA FORMATION --- p.81
Chapter 5.1 --- INTRODUCTION --- p.82
Chapter 5.2 --- MATERIALS AND METHODS --- p.84
Chapter 5.2.1 --- Materials --- p.84
Chapter 5.2.2 --- Grafting of pig saphenous veins and adenoviral transfection --- p.84
Chapter 5.2.3 --- Histologic and morphometric analysis of the vein graft --- p.87
Chapter 5.2.4 --- Immunocytochemistry --- p.87
Chapter 5.2.5 --- Data analysis and statistics --- p.88
Chapter 5.3 --- RESULTS --- p.89
Chapter 5.3.1 --- Histologic and morphometric analysis of the vein graft --- p.89
Chapter 5.3.2 --- Overexpression of TIMP-3 in porcine interposition grafts --- p.91
Chapter 5.3.3 --- Endothelial cell coverage and VSMCs content --- p.92
Chapter 5.3.4 --- Inflammation in vein grafts --- p.92
Chapter 5.4 --- DISCUSSION --- p.97
Chapter Chapter VI --- SUMMARY AND DISCUSSION OF MAJOR FINDINGS --- p.103
Chapter 6.1 --- SUMMARY AND DISCUSSION --- p.104
Chapter 6.1.1 --- The role of BMP4 in the pathogenesis of venous endothelial dysfunction --- p.104
Chapter 6.1.2 --- The involvement of osteopontin in the process of vein graft remodeling --- p.105
Chapter 6.1.3 --- Sustained benefits of adenoviruses-mediated TIMP-3 gene transfer in reducing vein graft neointima formation --- p.106
Chapter 6.1.4 --- The inflammatory responses induced by adenoviral transfection --- p.106
Chapter 6.1.5 --- Perspectives: novel therapeutic targets and clinical translation --- p.107
Chapter 6.2 --- CONCLUSIONS --- p.108
REFERENCES --- p.109
PUBLICATION LIST --- p.144