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.

Modelo de caracterización cerebral del área anorrectal mediante técnicas de neuroimagen para su utilización posterior en pacientes con incontinecia fecal

Resumen: La incontinencia fecal es una patología con importantes implicaciones sociosanitarias, con un tratamiento complejo y no siempre satisfactorio, especialmente la incontinencia fecal idiopática. El sistema nervioso central regula los procesos de continencia y defecación. Los estudios de neuroimagen han demostrado ser útiles para caracterizar las áreas cerebrales que controlan el área anorrectal. A partir de un grupo de voluntarias sanas, se ha creado un modelo de caracterización de estas áreas cerebrales anorrectales, que podrá ser utilizado posteriormente para compararlo con un grupo de pacientes con incontinencia fecal idiopática, estudiando posibles diferencias y posibles opciones terapéuticas.

The effects of sevoflurane and halothane anesthesia on cerebral blood flow velocity in children.

We compared cerebral blood flow velocity during anesthesia with sevoflurane and halothane in 23 children admitted for elective surgery (age, 0.4-9.7 yr; median age, 1.9 yr; ASA physical status I-II). Inhaled induction was performed in a randomized sequence with sevoflurane or halothane. Under steady-state conditions, cerebral blood flow velocity (systolic [V(s)], mean [V(mn)], and diastolic [VD]) were measured by a blinded investigator using transcranial pulsed Doppler ultrasonography. The anesthetic was then changed. CBFV measurements were repeated after washout of the first anesthetic and after steady-state of the second (equivalent minimal alveolar concentration to first anesthetic). The resistance index was calculated. VD and V(mn) were significantly lower during sevoflurane (V(mn) 1.35 m/s) than during halothane (V(mn) 1.50 m/s; P = 0.001), whereas V(s) was unchanged. The resistance index was lower during halothane (P < 0.001). Our results indicate lower vessel resistance and higher mean velocity during halothane than during sevoflurane. IMPLICATIONS: The mean cerebral blood flow velocity is significantly decreased in children during inhaled anesthesia with sevoflurane than during halothane. This might be relevant for the choice of anesthetic in children with risk of increased intracranial pressure, neurosurgery, or craniofacial osteotomies.