Paclitaxel-eluting biodegradable synthetic vascular prostheses: a step towards reduction of neointima formation?

BACKGROUND: Clinical small-caliber vascular prostheses are unsatisfactory. Reasons for failure are early thrombosis and late intimal hyperplasia. We thus prepared biodegradable small-caliber vascular prostheses using electrospun polycaprolactone (PCL) with slow-releasing paclitaxel (PTX), an antiproliferative drug. METHODS AND RESULTS: PCL solutions containing PTX were used to prepare nonwoven nanofibre-based 2-mm ID prostheses. Mechanical morphological properties and drug loading, distribution, and release were studied in vitro. Infrarenal abdominal aortic replacement was carried out with nondrug-loaded and drug-loaded prostheses in 18 rats and followed for 6 months. Patency, stenosis, tissue reaction, and drug effect on endothelialization, vascular remodeling, and neointima formation were studied in vivo. In vitro prostheses showed controlled morphology mimicking extracellular matrix with mechanical properties similar to those of native vessels. PTX-loaded grafts with suitable mechanical properties and controlled drug-release were obtained by factorial design. In vivo, both groups showed 100% patency, no stenosis, and no aneurysmal dilatation. Endothelial coverage and cell ingrowth were significantly reduced at 3 weeks and delayed at 12 and 24 weeks in PTX grafts, but as envisioned, neointima formation was significantly reduced in these grafts at 12 weeks and delayed at 6 months. CONCLUSIONS: Biodegradable, electrospun, nanofibre, polycaprolactone prostheses are promising because in vitro they maintain their mechanical properties (regardless of PTX loading), and in vivo show good patency, reendothelialize, and remodel with autologous cells. PTX loading delays endothelialization and cellular ingrowth. Conversely, it reduces neointima formation until the end point of our study and thus may be an interesting option for small caliber vascular grafts.

Thrombolyse de l'accident vasculaire cérébral ischémique aigu: rôles du praticien et de l'hôpital périphérique [Thrombolysis of acute ischemic cerebral vascular accident: roles of the physician and the peripheral hospital]

Thrombolysis administered intravenously within 3 hours (or within 6 hours intra-arterially) after symptoms onset improves the functional outcome of acute ischemic stroke patients. In Switzerland this treatment is only performed by specialized centers. At the level of a community hospital or a general practitioner, the management is based on the appropriate selection of patients in whom thrombolysis could be indicated, followed by their immediate transfer to a reference medical center. Because of the very short therapeutic window, specific criteria have to be used. We present the guidelines of Les Cadolles Hospital in Neuchâtel established in collaboration with the Department of Neurology of the University Hospital of Lausanne and a retrospective analysis of emergency admissions for suspected stroke at Les Cadolles between January 1st 2001 and December 31st 2002.

Effets hémodynamiques d'un inhibiteur de l'effet vasculaire de la vasopressine chez des patients avec insuffisance cardiaque congestive [Hemodynamic effects of an inhibitor of the vascular effects of vasopressin in patients with congestive heart failure]

To assess the role of vasopressin (AVP) in congestive heart failure (CHF), we investigated 10 patients with CHF refractory to conventional treatment, before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution, and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients there was no significant hemodynamic and cutaneous blood flow response to the AVP antagonist. Plasma AVP was 2.3 +/- 0.8 pg/ml and plasma osmolality 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP was 55 pg/ml and plasma osmolality 290 mosm/kg. He responded to the AVP antagonist with a marked decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously cardiac index increased from 1.1 to 2.21 X min-1 X m-2 and cutaneous blood flow rose 5-fold. Thus, most patients with CHF have only moderately elevated plasma AVP and its role in determining peripheral vascular resistance appears to be limited. AVP may become important in rare patients presenting with marked hemodynamic instability and very high plasma AVP.

Photodynamic induced uptake of liposomal doxorubicin to rat lung tumors parallels tumor vascular density.

BACKGROUND: Visudyne®-mediated photodynamic therapy (PDT) at low drug/light conditions has shown to selectively enhance the uptake of liposomal doxorubicin in subpleural localized sarcoma tumors grown on rodent lungs without causing morphological alterations of the lung. The present experiments explore the impact of low-dose PDT on liposomal doxorubicin (Liporubicin™) uptake to different tumor types grown on rodent lungs. MATERIAL AND METHODS: Three groups of Fischer rats underwent subpleural generation of sarcoma, mesothelioma, or adenocarcinoma tumors on the left lung. At least five animals of each group (sarcoma, n = 5; mesothelioma, n = 7; adenocarcinoma, n = 5) underwent intraoperative low-dose (10 J/cm(2) at 35 mW/cm(2) ) PDT with 0.0625 mg/kg Visudyne® of the tumor and the lower lobe. This was followed by intravenous (IV) administration of 400 µg Liporubicin™. After a circulation time of 60 min, the tumor-bearing lung was processed for HPLC analyses. At least five animals per group underwent the same procedure but without PDT (sarcoma, n = 5; mesothelioma, n = 5; adenocarcinoma, n = 6). Five untreated animals per group underwent CD31 immunostaining of their tumors with histomorphometrical assessment of the tumor vascularization. RESULTS: Low-dose PDT significantly enhanced Liporubicin™ uptake to all tumor types (sarcoma, P = 0.0007; mesothelioma, P = 0.001; adenocarcinoma, P = 0.02) but not to normal lung tissue compared to IV drug administration alone. PDT led to a significantly increased ratio of tumor to lung tissue drug uptake for all three tumor types (P < 0.05). However, the tumor drug uptake varied between tumor types and paralleled tumor vascular density. The vascular density was significantly higher in sarcoma than in adenocarcinoma (P < 0.001) and mesothelioma (P < 0.001), whereas there was no significant difference between adenocarcinoma and mesothelioma. CONCLUSION: Low-dose Visudyne®-mediated PDT selectively enhances the uptake of systemically administered liposomal doxorubicin in tumors without affecting the drug uptake to normal lung. However, drug uptake varied significantly between tumor types and paralleled tumor vascular density.

Eficacia del implante Ex-press en el tratamiento del glaucoma crónico de ángulo abierto

Estudi observacional i prospectiu que analitza la eficàcia de l’Ex-press mini glaucoma shunt en 20 ulls que presenten un control deficient de la PIO amb el tractament mèdic i es practica cirurgia. El període de seguiment és d’un any i s’analitza el descens de la PIO a la setmana, al mes, als 6 mesos i a l’any en relació amb la PIO prèvia. Al mateix temps analitzarem la necessitat d’utilitzar tractament mèdic posterior a la intervenció quirúrgica i les complicacions derivades de la utilització de l’implant.

Cirugía combinada de facoemulsificación de la catarata y esclerectomía profunda no perforante con implante supracoroideo: resultados a un año

S’ha avaluat l’efectivitat de la cirurgia combinada de facoemulsificació i esclerectomia profunda no perforant amb implant supracoroideu en 20 ulls de 16 pacients. Als 12 mesos de la cirurgia, s’ha observat una reducció significativa de la pressió intraocular mitjana de 22,8mmHg a 18mmHg, un descens del número de col•liris de 2,5 de mitjana en el preoperatori a 0,9 a l’any, així com una milloria significativa de l’agudesa visual sense un augment de complicacions relacionades amb l’implant utilitzat.

Incidencia de hipertensión ocular y glaucoma agudo por bloqueo pupilar tras implante de lente intraocular fáquica tipo ICL. Resultados anatómicos y funcionales a corto y medio plazo. Resultados preliminares

L'implant d’una lent intraocular fàquica tipus ICL (Implantable Collamer Lens) pot produir glaucoma agut per tancament angular degut a un bloqueig pupil•lar amb el consegüent augment de la pressió intraocular, el mecanisme i epidemiologia del qual no són ben coneguts. Aquest estudi preliminar pretén avaluar la incidència d'hipertensió ocular i glaucoma agut per tancament angular degut a bloqueig pupil·lar després de l'implant d'una lent posterior fàquica tipus ICL i plantejar hipòtesis sobre el seu mecanisme fisiopatològic.

Tetralogía de Fallot: rescate evolutivo del remodelado ventricular derecho tras la sustitución valvular pulmonar

La insuficiencia pulmonar después de la reparación de la Tetralogía de Fallot ocasiona una dilatación del ventrículo derecho, IT y/o empeoramiento de la CF. El momento de la cirugía viene marcado por la presencia de la clínica y/o dilatación ventrículo derecho. El motivo del presente estudio es realizar una revisión de los pacientes sometidos a sustitución valvular pulmonar, un seguimiento clínico y ecocardiográfico. MÉTODOS Desde enero 2003 a enero 2009, 33 pacientes fueron sometidos a una cirugía de sustitución valvular pulmonar. El 41 % de los pacientes fueron mujeres y el 59 % varones. La edad media de los pacientes fue de 31,3 años, ( 18 - 63 a ). La edad media de la primera intervención fue a los 3,8 años ( 6 meses – 28 años ). Sólo un paciente no había sido sometido a ningún tipo de intervención en la infancia, realizándose una cirugía paliativa – correctora a los 28 años. La indicación de intervención quirúrgica vino marcada por la presencia de clínica en 11 pacientes ( 37 %) y por dilatación VD, ( única o asintomática) en 18 pacientes ( 62%). RESULTADOS No hubo mortalidad operatoria con una estancia media post IQ de 15,21 días ( 9- 27 días). Se analizan los resultados quirúrgicos de estos pacientes a tres niveles: Clínica y tolerancia al esfuerzo en postoperatorio inmediato y tardío. Eventos arrítmicos en el postoperatorio inmediato y seguimiento y Parámetros ecocardiográficos en postoperatorio inmediato y tardío. (Dimensiones cavidades derechas y función contráctil del VD ( TAPSE )).En el seguimiento al año de la intervención ningún paciente presentaba clínica de IP. El 67 % de los pacientes fueron intervenidos manteniéndose asintomáticos con un 37% ( 11 pacientes ) de eventos arrítmicos pre cirugía ( 9 ; 31 % pacientes) fueron sometidos a ablación precirugía y 3 pacientes ( 10 %) requirieron implante de un dispositivo DAI. Después de la cirugía el 86 % de los pacientes, 24 pacientes, se mantenían en CF I; 3 pacientes ( 10 %) continuaron presentando eventos arrítmicos y un solo paciente requirió implante de DAI. El remodelado del VD al año y medio de seguimiento presentó una reducción del 11 % respecto al diámetro teledistólico precirugía ( DTDV x 54,43 ( 41-70 mm), postcirugía ( DTDV x 44,29 ( 32-61), p ≤ 0,01; sin encontrar diferencias significativas en la reducción del dTS pre/postcirugía. La función del VD ( TAPSE pre IQ 16,35 ( 13-229;postcirugía inmediata 15,54 ( 11-23) y al año 17,5. El gradiente medio es inferior al 15 mmHg en el 84 % de los pacientes portadores de válvula biológica. 11 pacientes ≤ 11 mmHg ( 44 %); 10 pacientes ≤ 15 mm Hg ( 40 %). CONCLUSIONES En este estudio realizado en el Hospital Vall d’Hebron, la sustitución valvular pulmonar en pacientes afectos de una Tetralogía de Fallot mejora los diámetros ventriculares, la función contráctil y por lo tanto la capacidad funcional de los mismos. En los pacientes sometidos a Estudio electrofisiológicos que no presentaron inducción de eventos arrítmicos ventriculares, no han presentado episodios arrítmicos tras la cirugía de sustitución valvular pulmonar. Todos los pacientes se mantienen en Clase funcional I tras la cirugía y libres de reintervención con un seguimiento medio de 16,9 ( 5-33 ) meses. Los factores de riesgo para presentar una peor evolución son un retraso en la corrección inicial de la TOF y por lo tanto aparición de enfermedad pulmonar por hipertensión vascular subyacente, edad avanzada en el momento del PVR, deterioro funcional preoperatorio con Clase Funcional según NYHA ( III- IV), o bien aparición de eventos arrítmicos.

Tratamiento quirúrgico del Hallux Valgus severo mediante cirugía percutánea. Estudio estadístico de los resultados clínicos, radiológicos y funcionales del tratamiento mediante la colocación de un implante intermetatarsiano

La cirurgia percutània en el tractament del hallux valgus és cada vegada més utilitzada, encara que compta amb limitacions en els casos severs. Es tracta d'un estudi retrospectiu en el qual s'analitzen estadísticament els resultats clínics, radiològics i funcionals del tractament quirúrgic del Hallux Valgus sever mitjançant cirurgia percutània amb la col•locació d'un dispositiu intermetatarsiano. Hi ha una bona correcció de l'angle intermetatarsiano i de l'angle hallux valgus, així com una millora clínica i funcional estadísticament significativa amb la utilització d'aquesta tècnica, sent els seus resultats comparables a aquells obtinguts amb la cirurgia oberta.

Changes in the vascular reactivity of the isolated tail arteries of spontaneous and renovascular hypertensive rats to endogenous and exogenous noradrenaline.

We have investigated the changes in the responses to noradrenaline of isolated tail arteries of spontaneously hypertensive (SHR) and renovascular hypertensive rats (Wistar-Kyoto: two-kidney, one-clip model, WKY:2K1C) compared with normotensive (Wistar-Kyoto, WKY) rats. Renovascular hypertension was induced by 4 weeks' unilateral renal artery clipping. Arteries were vasoconstricted with exogenous noradrenaline, electrical field stimulation or high potassium. The effects of the latter two stimuli were abolished by reserpine and so were presumably dependent on the presence of endogenous noradrenaline. In the SHR the maximal vasoconstriction produced by all three stimuli was greater than in WKY. Dose-response curves were steeper and there was no change in threshold. Vascular mass was greater. We interpret these results as showing an increase in vascular reactivity in the SHR caused by structural adaptation. The WKY:2K1C responses to noradrenaline could also be explained in terms of structural adaptation but there was no increase in vascular mass. Sensitivity to potassium and electrical stimulation was decreased, suggesting a defect in vascular neurotransmission. This was supported by the observations of a decreased arterial noradrenaline content and of decreased sensitivity to cocaine.

¿Som realment diferents els homes i les dones? Anàlisi de les diferències entre ambdós sexes en pacients amb malaltia vascular cerebral.

Es recullen les dades dels pacients amb ictus agut (isquèmic i hemorràgic) que ingressen al nostre servei i es comparen les dades epidemiològiques, clíniques i de pronòstic de dones i homes. En l'anàlisi comparatiu s’objectiven diferències en quant als factors de risc entre ambdós sexes. I es troben factors independents de mal pronòstic en els pacients amb un ictus isquèmic: l'antecedent de cardiopatia isquèmica, l’escala de rankin previ i l'escala canadenca a l'ingrés. En l'anàlisi de regressió logística es troben factors independents de mal pronòstic en els pacients amb una hemorràgia cerebral l'edat i l'escala canadenca a l'ingrés.

Implicación de la cocaína en la patología vascular cerebral

Revisió retrospectiva de pacients menors de 50 anys ingressats en el servei de Neurologia amb patologia cerebrovascular aguda des de gener 2006 fins desembre 2009, amb l'objectiu principal de descriure la implicació de la cocaïna en la patologia vascular cerebral en pacients joves. Es comparen 18 pacients amb nivells de cocaïna positius a l'ingrés i 79 pacients amb nivells negatius. De tots ells, es recullen diferents variables que defineixen el perfil de risc vascular, característiques clínico-topogràfiques de l'ictus i morbimortalitat associada als mateixos; finalment es realitza una anàlisi estadística de les dues poblacions.

Participation of connexin-based channels in the control of vascular function

SUMMARYIntercellular communication is achieved at specialized regions of the plasma membrane by gap junctions. The proteins constituting the gap junctions are called connexins and are encoded by a family of genes highly conserved during evolution. In adult mouse, four connexins (Cxs) are known to be expressed in the vasculature: Cx37, Cx40, Cx43 and Cx45. Several recent studies have provided evidences that vascular connexins expression and blood pressure regulation are closely linked, suggesting a role for connexins in the control of blood pressure. However, the precise function that each vascular connexin plays under physiological and pathophysiological conditions is still not elucidated. In this context, this work was dedicated to evaluate the contribution of each of the four vascular connexins in the control of the vascular function and in the blood pressure regulation.In the present work, we first demonstrated that vascular connexins are differently regulated by hypertension in the mouse aorta. We also observed that endothelial connexins play a regulatory role on eNOS expression levels and function in the aorta, therefore in the control of vascular tone. Then, we demonstrated that Cx40 plays a pivotal role in the kidney by regulating the renal levels of COX-2 and nNOS, two key enzymes of the macula densa known to participate in the control of renin secreting cells. We also found that Cx43 forms the functional gap junction involved in intercellular Ca2+ wave propagation between vascular smooth muscle cells. Finally, we have started to generate transgenic mice expressing specifically Cx40 in the endothelium to investigate the involvement of Cx40 in the vasomotor tone, or in the renin secreting cells to evaluate the role of Cx40 in the control of renin secretion.In conclusion, this work has allowed us to identify new roles for connexins in the vasculature. Our results suggest that vascular connexins could be interesting targets for new therapies caring hypertension and vascular diseases.