Utilidad de la ECMO sobre el injerto pulmonar disfuncionante en un modelo porcino estandarizado de trasplante unipulmonar / [Usefulness of ECMO on dysfunctional lung graft in a standardized porcine model of one-lung transplant]

Objetivo: Establecer un modelo de muerte encefálica y trasplante pulmonar y analizar el posible papel protector del oxigenador de membrana extracorpóreo (ECMO).Métodos: Se emplearon 20 cerdos hembras, 10 donantes y 10 receptoras. Las receptoras del Grupo A (n = 5) fueron sometidas a un trasplante unipulmonar izquierdo (Tx-UPI) sin ECMO. Las receptoras del Grupo B (n = 5) se sometieron a un Tx-UPI con ECMO venoarterial (ECMO-VA). Se recopilaron datos funcionales e histológicos en situación basal, a los 10 minutos de clampar el hilio derecho (Tiempo 1) y a las 2 horas (Tiempo 2). Se analizó la expresión proteica de marcadores de inflamación y de la ruta de hipoxia.Resultados: El modelo de muerte encefálica empleado, seguido de un tiempo de isquemia frío prolongado (20 horas) dio lugar a la aparición de un edema pulmonar severo. Tras el implante, 3 receptores del grupo A sobrevivieron hasta el Tiempo 2, falleciendo 2 por edema pulmonar masivo. Por el contrario, todos los animales del Grupo B sobrevivieron, siendo la PaO2 en ese momento de 462,72 mmHg. Hubo un incremento de la expresión de IL6, TNF, PCR, AC IX y el VEGF, así como un descenso en la expresión de IL8 y GLUT1, al usar la ECMO.Conclusiones: Se ha desarrollado un modelo porcino estandarizado y reproducible de muerte encefálica, que simula el proceso clínico de la donación pulmonar. Este modelo puede servir de plataforma para investigar posibles dianas terapéuticas. (AU)

Objective: Establish a model of brain death and lung transplantation and analyze the possible protective role of extracorporeal membrane oxygenation (ECMO).Methods: 20 female pigs were used, 10 donors and 10 recipients. Group A recipients (n = 5) underwent left-sided single- lung transplantation (LUCT-Tx) without ECMO. Group B recipients (n = 5) underwent ICU-Tx with venoarterial ECMO (VA-ECMO). Functional and histological data were collected at baseline, 10 minutes after clamping the right hilum (Time 1) and 2 hours (Time 2). Protein expression of inflammation markers and the hypoxia pathway was analyzed.Results: The brain death model used, followed by a prolonged cold ischemia time (20 hours) gave rise to the appearance of severe pulmonary edema. After implantation, 3 group A recipients survived until Time 2, with 2 dying from massive pulmonary edema. In contrast, all the animals in Group B survived, with PaO2 at that time being 462.72 mmHg. There was an increase in the expression of IL6, TNFα, CRP, AC IX and VEGF, as well as a decrease in the expression of IL8 and GLUT1, when using ECMO.Conclusions: A standardized and reproducible porcine model of brain death has been developed, which simulates the clinical process of lung donation. This model can serve as a platform to investigate possible therapeutic targets. (AU)

Influence of general anaesthesia on the intravenous acetaminophen pharmacokinetics in Beagle dogs.

OBJECTIVE: To determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs. STUDY DESIGN: Prospective, crossover, randomized experimental study. ANIMALS: A group of nine healthy Beagle dogs. METHODS: Acetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg-1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 µg kg-1) intramuscularly, anaesthesia was induced with propofol (2-3 mg kg-1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe'Iso 1.3-1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05). RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94-3.65) and 1.72 (0.89-2.60) L kg-1, clearance values 1.52 (0.71-2.30) and 1.60 (0.91-1.78) L kg-1 hour-1 or terminal elimination half-life values 2.45 (1.45-8.71) and 3.57 (1.96-6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded. CONCLUSIONS AND CLINICAL RELEVANCE: IV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.

Cardiorespiratory and anaesthetic effects of two continuous rate infusions of dexmedetomidine in alfaxalone anaesthetized dogs.

Six Beagles were used in this prospective randomised crossover experimental study. Dexmedetomidine was administered at 0, 1 or 2 µg/kg IV for group C, LDA and HDA, respectively. Animals were induced and maintained with alfaxalone at 0.07 mg/kg/min with a CRI dexmedetomidine dose of 0, 0.5 or 1 µg/kg/h for group C, LDA and HDA, respectively. Cardiorespiratory variables, arterial blood gases and depth of anaesthesia were recorded. The recovery times and quality of recovery were scored. Group HDA produced a greater increase in the depth of anaesthesia than LDA. However, with both protocols, CI was halved compared to normal values in dogs. The use of oxygen before and during the anaesthetic maintenance is advisable, mainly if dexmedetomidine is going to be use as a pre-medicant and maintenance agent. The quality of recovery was better in groups receiving dexmedetomidine, without causing an increase in recovery time.