An artificial nanoemulsion carrying paclitaxel decreases the transplant heart vascular disease: A study in a rabbit graft model

Objective: In previous studies cholesterol-rich nanoemulsions (LDE) resembling low-density lipoprotein were shown to concentrate in atherosclerotic lesions of rabbits. Lesions were pronouncedly reduced by treatment with paclitaxel associated with LDE. This study aimed to test the hypothesis of whether LDE-paclitaxel is able to concentrate in grafted hearts of rabbits and to ameliorate coronary allograft vasculopathy after the transplantation procedure. Methods: Twenty-one New Zealand rabbits fed 0.5% cholesterol were submitted to heterotopic heart transplantation at the cervical position. All rabbits undergoing transplantation were treated with cyclosporin A (10 mg . kg(-1) . d(-1) by mouth). Eleven rabbits were treated with LDE-paclitaxel (4 mg/kg body weight paclitaxel per week administered intravenously for 6 weeks), and 10 control rabbits were treated with 3 mL/wk intravenous saline. Four control animals were injected with LDE labeled with [(14)C]-cholesteryl oleate ether to determine tissue uptake. Results: Radioactive LDE uptake by grafts was 4-fold that of native hearts. In both groups the coronary arteries of native hearts showed no stenosis, but treatment with LDE-paclitaxel reduced the degree of stenosis in grafted hearts by 50%. The arterial luminal area in grafts of the treated group was 3-fold larger than in control animals. LDE-paclitaxel treatment resulted in a 7-fold reduction of macrophage infiltration. In grafted hearts LDE-paclitaxel treatment reduced the width of the intimal layer and inhibited the destruction of the medial layer. No toxicity was observed in rabbits receiving LDE-paclitaxel treatment. Conclusions: LDE-paclitaxel improved posttransplantation injury to the grafted heart. The novel therapeutic approach for heart transplantation management validated here is thus a promising strategy to be explored in future clinical studies. (J Thorac Cardiovasc Surg 2011;141:1522-8)

Objective characterization of the course of the parasellar internal carotid artery using mathematical tools

Background Along the internal carotid artery (ICA), atherosclerotic plaques are often located in its cavernous sinus (parasellar) segments (pICA). Studies indicate that the incidence of pre-atherosclerotic lesions is linked with the complexity of the pICA; however, the pICA shape was never objectively characterized. Our study aims at providing objective mathematical characterizations of the pICA shape. Methods and results Three-dimensional (3D) computer models, reconstructed from contrast enhanced computed tomography (CT) data of 30 randomly selected patients (60 pICAs) were analyzed with modern visualization software and new mathematical algorithms. As objective measures for the pICA shape complexity, we provide calculations of curvature energy, torsion energy, and total complexity of 3D skeletons of the pICA lumen. We further measured the posterior knee of the so-called ""carotid siphon"" with a virtual goniometer and performed correlations between the objective mathematical calculations and the subjective angle measurements. Conclusions Firstly, our study provides mathematical characterizations of the pICA shape, which can serve as objective reference data for analyzing connections between pICA shape complexity and vascular diseases. Secondly, we provide an objective method for creating Such data. Thirdly, we evaluate the usefulness of subjective goniometric measurements of the angle of the posterior knee of the carotid siphon.

Three-dimensional description and mathematical characterization of the parasellar internal carotid artery in human infants

Inside the `cavernous sinus` or `parasellar region` the human internal carotid artery takes the shape of a siphon that is twisted and torqued in three dimensions and surrounded by a network of veins. The parasellar section of the internal carotid artery is of broad biological and medical interest, as its peculiar shape is associated with temperature regulation in the brain and correlated with the occurrence of vascular pathologies. The present study aims to provide anatomical descriptions and objective mathematical characterizations of the shape of the parasellar section of the internal carotid artery in human infants and its modifications during ontogeny. Three-dimensional (3D) computer models of the parasellar section of the internal carotid artery of infants were generated with a state-of-the-art 3D reconstruction method and analysed using both traditional morphometric methods and novel mathematical algorithms. We show that four constant, demarcated bends can be described along the infant parasellar section of the internal carotid artery, and we provide measurements of their angles. We further provide calculations of the curvature and torsion energy, and the total complexity of the 3D skeleton of the parasellar section of the internal carotid artery, and compare the complexity of this in infants and adults. Finally, we examine the relationship between shape parameters of the parasellar section of the internal carotid artery in infants, and the occurrence of intima cushions, and evaluate the reliability of subjective angle measurements for characterizing the complexity of the parasellar section of the internal carotid artery in infants. The results can serve as objective reference data for comparative studies and for medical imaging diagnostics. They also form the basis for a new hypothesis that explains the mechanisms responsible for the ontogenetic transformation in the shape of the parasellar section of the internal carotid artery.

Estenose da fossa intercondilar após estabilização articular com retalho de fáscia lata em cães

Determinaram-se os índices de largura da fossa intercondilar (FI), após transecção do ligamento cruzado cranial em nove cães adultos submetidos à estabilização articular com retalho de fáscia lata. Os joelhos foram alocados em dois grupos, sendo o joelho direito (GI) submetido à incisuroplastia troclear (ITR) e posterior estabilização articular, e o joelho esquerdo submetido somente à substituição ligamentar (GC). Cada grupo foi dividido em três subgrupos correspondentes aos momentos de eutanásia aos 30, 90 e 180 dias de pós-operatório. Os índices de largura da FI foram determinados, macroscópica e radiograficamente, pela mensuração da abertura cranial da FI nos terços cranial, médio e caudal, e indexados em relação à largura epicondilar. Observou-se aumento significativo dos índices macroscópicos e radiográficos nas articulações do GI, sendo estes estatisticamente diferentes daqueles das articulações de GC. Não foi observada estenose intercondilar nos joelhos de GC após a estabilização articular. Conclui-se que a estabilização articular com retalho de fáscia lata preveniu a estenose da fossa intercondilar, e que a ITR promoveu o alargamento permanente dessa estrutura.

Extrinsic compression of popliteal artery in asymptomatic athlete and non-athlete individuals - A comparative study using duplex scan (color duplex sonography)

Aim. Extrinsic compression of the popliteal artery and absence of surrounding anatomical abnormalities characterize the functional popliteal artery entrapment syndrome (PAES). The diagnosis is confirmed to individuals who have typical symptoms of popliteal entrapment and occlusion or important stenosis of the popliteal artery with color duplex sonography (CDS), magnetic resonance imaging (MRI) or arteriography during active plantar flexion-extension maneuvers. However, variable result findings in normal asymptomatic subjects have raised doubts as to the validity of these tests. The purpose of this study was to compare the frequency of popliteal artery compression in 2 groups of asymptomatic subjects, athletes and non-athletes.Methods. Forty-two individuals were studied. Twenty-one subjects were indoor soccer players, and 21 were sedentary individuals. Physical activity was evaluated through questionnaires, anthropometric measurements, and cardiopulmonary exercise test. Evaluation of popliteal artery compression was performed in lower limbs with CDS, ankle-brachial index (ABI) measurements and continuous wave Doppler of the posterior tibial artery.Results. The athletes studied fulfilled the criteria of high level of physical activity whereas sedentary subjects met the criteria of low level of activity. Popliteal artery compression was observed with CDS in 6 (14.2%) studied subjects; 2 of whom (4.7%) were athletes and 4 (9.5%) were non-athletes. This difference was not statistically significant (p=0.21). Doppler of the tibial arteries and ABI measurements gave good specificity and sensibility in the identification of popliteal artery compression.Conclusion. The frequency of popliteal artery compression during maneuvers in normal subjects was 14.2% irrespective of whether or not they performed regular physical activities. Both Doppler and ABI showed good agreement with CDS and should be considered in screening popliteal arteries in individuals suspected of PAES.

O bloqueio do sistema renina-angiotensina atenua a remodelação cardíaca de ratos submetidos a estenose aórtica

OBJETIVO: Avaliar o papel do bloqueador dos receptores AT1 e do inibidor da enzima conversora da angiotensina na remodelação cardíaca induzida por estenose aórtica em ratos. MÉTODOS: Ratos Wistar foram divididos em 4 grupos: controle (C, n=13), estenose aórtica (EAo, n=11), EAo com lisinopril, 20 mg/kg/dia (LIS, n=11) e EAo com losartan, 40 mg/kg/dia (LOS, n=9). Os tratamentos foram iniciados 3 dias antes da cirurgia. Após 6 semanas, os animais foram submetidos ao estudo ecocardiográfico, quantificação da concentração de hidroxiprolina e da área seccional (CSA) miocitária do ventrículo esquerdo (VE). RESULTADOS: A EAo induziu aumento da espessura da parede do VE. Os animais LIS e LOS não apresentaram diferença em relação aos animais controles. Os ratos EAo e LIS apresentaram maiores diâmetros do átrio esquerdo que os ratos controles, enquanto nos animais LOS não houve diferença. Os animais com EAo apresentaram maiores valores da porcentagem de encurtamento que os controle. Esse fato não foi modificado com LIS ou LOS. A CSA dos animais do grupo EAo foi maior que a dos controle. Entretanto, o tratamento com LOS e com LIS atenuou o aumento da área induzida pela EAo. A EAo resultou em aumento na concentração de HOP, enquanto o grupo LOS não apresentou diferença em relação ao grupo controle. CONCLUSÃO: O bloqueio do sistema renina-angiotensina, com bloqueador AT1 e com IECA, pode atenuar o desenvolvimento de hipertrofia cardíaca, porém só o bloqueio dos receptores AT1 atenua a fibrose intersticial do VE.

Critérios ecocardiográficos para definição de graus de disfunção ventricular em ratos portadores de estenose aórtica

OBJETIVO: O objetivo deste estudo foi identificar variáveis ecocardiográficas que definam graus de disfunção cardíaca em ratos com estenose aórtica (EAo). MÉTODOS: Ratos Wistar (n = 23), machos (90-100 g), foram submetidos a cirurgia para indução de EAo. As variáveis ecocardiográficas analisadas foram: diâmetros diastólico do ventrículo esquerdo (DDVE) e sistólico do átrio esquerdo em valores absolutos e normalizados para o peso corporal; diâmetro sistólico do VE (DSVE); três índices de encurtamento do VE (% de encurtamento endocárdico, %Enc.Endo; % de encurtamento miocárdico, %Enc.Mio; e velocidade de encurtamento da parede posterior do VE, VEPP); e índice de massa do VE (IMVE). Essas variáveis foram utilizadas para a análise de agrupamento (cluster analysis). RESULTADOS: A análise de agrupamento possibilitou separar os ratos com EAo em dois grupos: disfunção leve (n = 13) e disfunção severa (n = 9). Os intervalos de confiança das seguintes variáveis não apresentaram superposição dos seus valores: DDVE, DSVE, %Enc.Endo, %Enc.Mio, IMVE e VEPP. CONCLUSÃO: A utilização conjunta dos intervalos de confiança dessas variáveis permite identificar dois grupos de ratos com estenose aórtica e diferentes graus de comprometimento cardíaco, possibilitando a realização de estudos longitudinais com grupos homogêneos de animais.

Impacto da hipertensão arterial no remodelamento ventricular, em pacientes com estenose aórtica

FUNDAMENTO: A hipertrofia ventricular esquerda (HVE) é comum em pacientes com hipertensão arterial sistêmica (HAS) e estenose aórtica (EAo) e, com certa frequência, encontramos associação entre estas patologias. Mas, em tal situação, não está clara a importância de cada uma na HVE. OBJETIVO: 1 - Avaliar em pacientes portadores de EAo, submetidos previamente a estudo ecocardiográfico, a magnitude da HVE, nos casos de EAo isolada e associada à HAS; 2 - Avaliar o padrão de remodelamento geométrico nas duas situações. MÉTODOS: Estudo retrospectivo, observacional e transversal, incluindo 298 pacientes consecutivos, com EAo ao ecocardiograma. HVE foi considerada para massa miocárdica > 224g em homens e > 162g em mulheres. Os pacientes foram classificados como portadores de EAo leve (gradiente máximo < 30,0 mmHg), moderada (entre 30 e 50,0 mmHg) e grave (> 50,0 mmHg), além disso, foram separados em dois subgrupos: com e sem HAS. RESULTADOS: Nos três níveis de lesão aórtica, a massa ventricular esquerda foi maior na EAo associada à HAS do que na EAo isolada (EAo leve: 172 ± 45 vs 223 ± 73g, p < 0,0001; EAo moderada: 189 ± 77 vs 245 ± 81g, p = 0,0313; EAo grave: 200 ± 62 vs 252 ± 88g, p = 0,0372). Presença de HAS esteve associada a maior risco de HVE (OR = 2,1,IC95%:1,2-3,6; p = 0,012). Pacientes com EAo grave e HAS apresentaram predomínio de hipertrofia concêntrica, quando comparados com aqueles normotensos (p = 0,013). CONCLUSÃO: em pacientes com EAo, a presença de HAS foi um fator adicional de aumento da massa ventricular esquerda, interferindo também na geometria ventricular.

Alterações epiteliais e cartilaginosas em cirurgia traqueal: estudo experimental em cobaias

FORMA DE ESTUDO: Experimental. MATERIAL E MÉTODO: Transplante homógeno de traquéia foi realizado em 51 cobaias (Cavia Porcellus). RESULTADO: Observamos reepitelização do enxerto a partir da traquéia receptora da cobaia, evoluindo de epitélio escamoso de 1 a 3 células nos animais com 3, 7 e 14 dias de observação para epitélio ciliado após 60 a 120 dias do transplante. A viabilidade do enxerto traqueal era boa, com reabsorção parcial da cartilagem e formação de estenose traqueal parcial, mas sem sinais clínicos evidentes de obstrução respiratória durante o tempo de observação dos animais.

Lesões sequelares na laringe em pacientes com paracoccidiodomicose

A Paracoccidioidomicose (PCM) é uma doença sistêmica que em sua forma sequelar se caracteriza por manifestações clínicas relacionadas às alterações anatômicas ou funcionais de órgãos e sistemas comprometidos no período de estado. OBJETIVO: Descrever as alterações anatômicas e funcionais laríngeas sequelares em pacientes com paracoccidioidomicose. MATERIAL E MÉTODOS: Estudo retrospectivo, sendo avaliados 49 pacientes do sexo masculino, na faixa etária de 30 a 60 anos, entre 1999 a 2004, com diagnóstico de PCM em acompanhamento pela disciplina de Moléstias Infecciosas e Parasitárias, confirmado pela demonstração do fungo em escarro, exame citológico ou histopatológico. RESULTADOS: As pregas vocais foram a estrutura laríngea mais afetada, em 67% dos pacientes verificaram-se alterações. A epiglote estava acometida em 55% dos casos. As pregas ariepiglóticas tinham modificações em 53% dos pacientes. As pregas vestibulares estavam alteradas em 46% dos casos. em 40% dos casos verificaram-se alterações em aritenoides. Na fonação, 28% tinham limitação ao movimento das cordas vocais, paresia unilateral ocorreu em 4% casos. em 24% havia restrição da luz supraglótica e 4% tinham estenose glótica, sendo que 2% precisaram de traqueotomia. CONCLUSÃO: As lesões sequelares na laringe devido à infecção pelo P. brasilienses são extensas e causam restrições funcionais na maioria dos casos.

Fatores associados à recorrência da infecção do trato urinário em crianças

OBJETIVOS: verificar a freqüência de infecção urinária recorrente (ITU) e avaliar os fatores associados à recorrência da ITU em crianças. MÉTODOS: estudo retrospectivo de 95 pacientes com seguimento de um ano (68 meninas e 27 meninos, mediana de idade três anos). As variáveis estudadas foram: sexo, idade, febre, constipação, tipo de bactéria, refluxo vésico-ureteral (RVU), anormalidades na cintilografia renal com ácido dimercaptosuccínico (DMSA). RESULTADOS: infecção urinária recorrente ocorreu em 49,5% crianças (19 com trato urinário normal, 19 com RVU e 9 com estenose da junção pielocalicial). Comparando o grupo com ITU recorrente com o grupo sem ITU recorrente não se encontrou diferença significativa entre sexos, presença de febre, constipação e anormalidades na cintilografia renal com DMSA. A ITU recorrente foi significativamente maior nas crianças com um ano ou menos, naquelas menores de dois anos com RVU, nas com bactéria diferente da Escherichia coli e sem profilaxia antibacteriana. Os fatores de risco significativos para a recorrência ITU foram idade < 2 anos (OR = 3,83) e refluxo vésico-ureteral (OR = 4,95). CONCLUSÕES: por causa da elevada freqüência de ITU recorrente é importante o seguimento regular de grupo de crianças com fatores de risco para ITU recorrente.

Laparoscopic management of iatrogenic lesions

Purpose: To present our series of patients who underwent laparoscopic correction of iatrogenic lesions and a review of the literature.Patients and Methods: We evaluated 23 patients who underwent laparoscopic correction of iatrogenic lesions. Thirteen patients had open surgery, 6 had an endoscopic procedure, and 4 had a laparoscopic approach as the first surgical procedure. Vesicovaginal fistulas (VVF) developed in seven patients after open abdominal hysterectomies, and 1 patient presented with a VVF after ureterolithotripsy. A urethral cutaneous fistula developed in one patient after a laparoscopic resection of endometriosis nodules, and 1 patient presented with a ureterovaginal fistula after a perineoplasty. Three patients presented with encrusted ureteral stents after ureterolithotripsy. Ureteral stenosis developed in seven patients: three after open abdominal surgery, three after ureteroscopy, and one after pyeloplasty. One patient had a ureteral injury during laparoscopic partial nephrectomy, and two patients had bowel injuries after a tension-free vaginal tape procedure and a laparoscopic radical prostatectomy.Results: All patients underwent laparoscopic correction of the iatrogenic injuries. One patient had an early recurrence of a VVF, and one patient had a recurrence of a ureteral stenosis. There was one conversion to open surgery because of technical difficulties and one major bleeding event that necessitated blood transfusion. A lower limb compartmental syndrome developed in one patient.Conclusion: Despite the small number of patients and different types of surgeries performed, laparoscopic management of iatrogenic lesions seems to be feasible and safe in experienced hands. Its precise role in the management of this stressful condition still needs to be determined.

Estenose de piloro em eqüino adulto

Neste trabalho, é descrito um caso de estenose hipertrófica de piloro diagnosticado por gastroscopia em um eqüino Quarto de Milha, de quatro anos de idade, que apresentava inapetência, emagrecimento progressivo, cólica, bruxismo e sialorréia. A gastroduodenite ulcerativa crônica e os espasmos prolongados foram as supostas causas da hipertrofia da musculatura circular do piloro, causando a estenose. O tratamento com substâncias antiulcerativas é paliativo e o acesso cirúrgico ao piloro no animal adulto é complexo, sendo o prognóstico duvidoso.

Growth hormone and heart failure: Oxidative stress and energetic metabolism in rats

Several evidences point for beneficial effects of growth hormone (GH) in heart failure (HF). Taking into account that HF is related with changes in myocardial oxidative stress and in energy generation from metabolic pathways, it is important to clarify whether GH increase or decrease myocardial oxidative stress and what is its effect on energetic metabolism in HF condition. Thus, this study investigated the effects of two different doses of GH on energetic metabolism and oxidative stress in myocardium of rats with HF. Male Wistar rats (n = 25) were submitted to aortic stenosis (AS). The HF was evidenced by tachypnea and echocardiographic criteria around 28 weeks of AS. The rats were then randomly divided into three groups: (HF) with HF, treated with saline (0.9% NaCl); (HF-GHI), treated with 1 mk/kg/day recombinant human growth hormone (rhGH), and (HF-GH2) treated with 2 mg/kg/day rhGH. GH was injected, subcutaneously, daily for 2 weeks. A control group (sham; n = 12), with the same age of the others rats was evaluated to confirm data for AS. HF had lower IGF-I (insulin-like growth factor-I) than sham-operated rats, and both GH treatments normalized IGF-I level. HF-GH1 animals had lower lipid hydroperoxide (LH), LH/total antioxidant substances (TAS) and glutathione-reductase than HF. Glutathione peroxidase (GSH-Px), hydroxyacyl coenzyme-A dehydrogenase, lactate dehydrogenase(LDH) were higher in HF-GH1 than in HF. HF-GH2 compared with HF, had increased LH/TAS ratio, as well as decreased oxidized glutathione and LDH activity. Comparing the two GH doses, GSH-Px, superoxide dismutase and LDH were lower in HF-GH2 than in HF-GHI. In conclusion, GH effects were dose-dependent and both tested doses did not aggravate the heart dysfunction. The higher GH dose, 2 mg/kg exerted detrimental effects related to energy metabolism and oxidative stress. The lower dose, 1 mg/kg GH exerted beneficial effects enhancing antioxidant defences, reducing oxidative stress and improving energy generation in myocardium of rats with heart failure. (c) 2007 Elsevier Ltd. All rights reserved.

GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD-INDUCED LEFT VENTRICULAR HYPERTROPHY

1. The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload-induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short-term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload-induced hypertrophy.2. Twenty-six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS-GH group) or saline (AAS-P group) for 14 days. Sham-operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis.3. Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS-P group than in the control group. However, in the AAS-GH group, PWSV was between that in the control and AAS-P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS-P and AAS-GH groups compared with control (10.34 +/- 1.29, 4.44 +/- 1.37 and 1.88 +/- 0.88%, respectively; P < 0.05) and was higher still in the AAS-P group compared with the AAS-GH group.4. The present study has shown that short-term administration of GH to rats with chronic pressure overload-induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.