RESUMEN
PURPOSE: Medialization procedures for unilateral vocal fold (VF) paralysis generally improve voice but do not fully replace dynamic VF adduction. Paralyzed VFs typically experience synkinetic reinnervation, which makes it feasible to elicit movement through electrical stimulation. We tested a novel laryngeal pacing implant capable of providing closed-loop (automatic) stimulation of a VF triggered by electromyography (EMG) potentials from the contralateral VF. METHOD: A custom, battery-powered, microprocessor-based stimulator was tested in eight dogs with bipolar electrodes implanted for recording EMG from the left VF and stimulating adduction of the right VF. A cuff electrode on the left recurrent laryngeal nerve (RLN) stimulated unilateral VF adduction, modeling voluntary control in anesthetized animals. Closed-loop stimulation was tested in both acute and chronic experiments. Synkinetic reinnervation was created in two animals by right RLN transection and suture repair to model unilateral VF paralysis. RESULTS: In all animals, left VF activation through RLN stimulation generated a robust EMG response that rapidly triggered stimulation of contralateral thyroarytenoid and lateral cricoarytenoid muscles, causing nearly simultaneous bilateral adduction. Optimal triggering of VF stimulation from elicited EMG was achieved using independent onset and offset thresholds. Real-time artifact blanking allowed closed-loop stimulation without self-perpetuating feedback, despite the proximity of recording and stimulation electrodes. CONCLUSIONS: Using a custom implant system, we demonstrated real-time closed-loop stimulation of one VF triggered by the activation of the contralateral VF. This approach could potentially restore dynamic glottic closure for reflexive behaviors or phonation in cases of unilateral VF paralysis with synkinetic reinnervation. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24492133.
Asunto(s)
Parálisis de los Pliegues Vocales , Pliegues Vocales , Animales , Perros , Electromiografía/métodos , Parálisis de los Pliegues Vocales/terapia , Músculos Laríngeos/fisiología , Fonación/fisiología , Estimulación Eléctrica/efectos adversosRESUMEN
During a previously reported program-wide Corynebacterium bovis outbreak, both immunocompetent depilated (dep/dep) mutant mice and transgenic mice that express the papillomavirus E6 oncoprotein became persistently infected with C. bovis. An orthokeratotic, hyperkeratotic, acanthotic dermatitis developed in the C. bovis-infected dep/dep mice, which remained C. bovis PCR-positive for >45 days prior to euthanasia as part of the program-wide C. bovis eradication effort. Since both affected strains of mice have altered skin homeostasis, immune status or the presence of hair may not alone be sufficient to explain strain susceptibility to C. bovis-related cutaneous disease. In order to avoid invalidation of preclinical studies due to C. bovis infection, it may be necessary to isolate immunodeficient mouse strains, implement facililty-wide surveillance for C. bovis, and sterilize equipment with vaporized hydrogen peroxide.
Asunto(s)
Infecciones por Corynebacterium/veterinaria , Ratones Desnudos/microbiología , Animales , Enfermedades Transmisibles/transmisión , Enfermedades Transmisibles/veterinaria , Corynebacterium , Infecciones por Corynebacterium/prevención & control , Infecciones por Corynebacterium/transmisión , Dermatitis/microbiología , Dermatitis/veterinaria , Epidermis/microbiología , Epidermis/patología , Hiperqueratosis Epidermolítica/veterinaria , Ratones , Enfermedades de los Roedores/microbiología , Piel/microbiología , Piel/patologíaRESUMEN
The optimal choice of euthanasia method for laboratory rodents depends on a number of factors, including the scientific goals of the study, the need to minimize animal pain and/or distress, applicable guidelines and laws, the training and proficiency of personnel, and the safety and emotional needs of the personnel performing the euthanasia. This manuscript aims to provide guidance to researchers so they may select the method of euthanasia that results in minimal experimental confounds, such as the creation of artifact and alteration of tissues and analytes. Specific situations addressed include euthanasia of large numbers of rodents and euthanasia of neonates. Recent literature supports the notion of significant strain-dependent differences in response to euthanasia methods such as CO2 inhalation. To assist researchers in selecting a strain-appropriate method of euthanasia, the authors present a summary of methodologies for assessing the effectiveness of euthanasia techniques, including elements and parameters for a scoring rubric to assess them.
Asunto(s)
Eutanasia Animal/métodos , Roedores , Bienestar del Animal , Animales , Animales de Laboratorio , Dióxido de Carbono/administración & dosificación , Guías como Asunto , Roedores/clasificación , Roedores/fisiologíaRESUMEN
Cynomolgus monkeys are often used in preclinical transplantation research. Performing liver transplantation in cynomolgus monkeys is challenging because they poorly tolerate portal vein clamping during the anhepatic phase. Finding an alternative to portal vein clamping is necessary before preclinical liver transplant models can be performed with reliable outcomes. We used 3 different techniques to perform 5 liver transplants in male cynomolgus macaques (weight, 7.4-10.8 kg; mismatched for MHC I and II; matched for ABO). In procedure A, we clamped the portal vein briefly, as in human transplants, as well as the superior mesentery artery to minimize congestion at the expense of temporary ischemia (n = 2). In procedure B, we performed a temporary portocaval shunt with extracorporeal venovenous bypass (n = 1). For procedure C, we developed an H-shunt system (modified portocaval shunt) with extracorporeal bypass (n = 2). Postoperative immunosuppression comprised cyclosporine A, mycophenolate mofetil, and steroids. Recipients in procedure A developed hemodynamic instability and were euthanized within 2 d. The recipient that underwent procedure B was euthanized within 11 d due to inferior vena caval thrombosis. The H-shunt in procedure C led to minimal PV congestion during the anhepatic phase, and both recipients reached the 21-d survival endpoint with good graft function. Our novel H-shunt bypass system resulted in successful liver transplantation in cynomolgus macaques, with long-term posttransplant survival possible. This technical innovation makes possible the use of cynomolgus monkeys for preclinical liver transplant tolerance models.
Asunto(s)
Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Hígado/veterinaria , Macaca fascicularis/cirugía , Derivación Portocava Quirúrgica/veterinaria , Anastomosis Quirúrgica/métodos , Anastomosis Quirúrgica/veterinaria , Animales , Femenino , Humanos , Pruebas de Función Hepática/veterinaria , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Masculino , Arterias Mesentéricas/cirugía , Modelos Animales , Vena PortaRESUMEN
We examined the efficacy of enrofloxacin administered by 2 different routes in a mouse model of sepsis. Male CD1 mice were infected with a bioluminescent strain of enteropathogenic Escherichia coli and treated with enrofloxacin either by injection or in drinking water. Peak serum levels were evaluated by using HPLC. Mice were monitored for signs of clinical disease, and infections were monitored by using bioluminescence imaging. Serum levels of enrofloxacin and the active metabolite ciprofloxacin were greater in the group treated by injection than in controls or the groups treated by administration in drinking water. Survival of the group treated with enrofloxacin injection was greater than that of controls and groups treated with enrofloxacin in the drinking water. Bioluminescence in the group treated with enrofloxacin injection was less than that in the groups treated with oral administration at 12 h and in the groups treated orally and the control group at 16 h. According to these findings, we recommend the use of injectable enrofloxacin at 5 mg/kg SC for mice with systemic infections.