Orthotopic total aortic root replacement model in adult sheep.

Prosthetic heart valves undergo mandatory preclinical animal testing prior to human clinical trials. Historically, a non-site-specific placement of a valve prosthesis has been commonly performed; however, recently site-specific placement continues to attract interest. Various animal models have been used for preclinical evaluation of both aortic and mitral valve prostheses; however, a universally accepted animal model for orthotopic total aortic root replacement with acceptable early and late mortality for long-term evaluation has been lacking. This article reports a successful orthotopic model for placement of tissue valve conduit prosthesis for total aortic root replacement in adult sheep. This model utilized preoperative echocardiographic assessment, specific intraoperative surgical techniques, and both early and late postoperative management therapies. The combination of all of these components resulted in a successful model for orthotopic placement of a tissue valve prosthesis for total aortic root replacement in adult sheep for potential long-term assessment.     

General use of animal models for investigation of the physiology of erection

In review, animal models have accounted significantly for the amazing strides made in the field of sexual dysfunction research. Fundamentally, they have offered a unique experimental approach to test many hypotheses regarding sexual function. Since their early use for sexual physiology research, there has been increasing sophistication using animals involving techniques for stimulating and monitoring sexual responses. One specific area that has been advanced is the use of conscious animal models to obtain a better sense of the natural contexts for sexual physiology and to avoid pharmacological interference associated with anesthetics. Another area of interest is the increasing use of simple but valid techniques to record and assess sexual responses. Efforts to develop and evaluate animal models that replicate disorders of sexual function have also been most advantageous. In the future, animal models will remain useful. The expanded applications of animal models include the study of predisposing disease states associated with sexual dysfunction and the study of all aspects of sexual dysfunction, in both male and female subjects. Continued judgment must be applied, understanding the advantages of one or another animal model, to explore questions and provide answers that are most scientifically relevant to the human condition. The promise of advancing therapies in this field indicates the additional prominent role for animals for the purposes of drug development.     

An in-vivo paradigm for the evaluation of stimulating electrodes for use with a visual prosthesis

BACKGROUND: Electrical stimulation of the visual cortex with surface electrodes is able to elicit basic visual perceptions in blind patients. The development of a visual prosthesis for the blind will require an in-vivo model for the optimization of cortical neurostimulation with multielectrode arrays. METHODS: In anaesthetized cats a bilateral craniotomy was performed and the dura was removed to expose the cerebral cortex. A prototype stimulating electrode array was placed on a gyrus in one hemisphere, and the transcallosal evoked response (TER) to cortical stimulation by this electrode array was recorded at a homologous region in the contralateral hemisphere. RESULTS: The stimulating electrode array elicited TER of short latency (6.9 ms) in the contralateral hemisphere. Bipolar stimulation of adjacent electrodes on the array evoked similar TER regardless of the polarity of stimulation. Electrodes spread apart on the array caused higher amplitude TER than electrodes placed close together. Multielectrode stimulation evoked lower amplitude TER than bipolar stimulation. CONCLUSIONS: This transcallosal model of cortical neurostimulation is a useful method to evaluate electrode arrays and stimulation techniques in the development of a visual prosthesis.     

The critical size defect as an experimental model for craniomandibulofacial nonunions

Little consistency has been manifest among investigators in choosing an appropriate experimental model for maxillofacial bone research. In an effort to develop a protocol for the experimental analysis of maxillofacial nonunions, previous studies using calvarial and mandibular defects as models were reviewed. The creation of nonunions in animals within the calvaria and mandible was size dependent. Defects of a size that will not heal during the lifetime of the animal may be termed critical size defects (CSDs). A rationale was postulated for testing bone repair materials (BRMs) using CSDs in a hierarchy of animal models. This rationale suggests that testing should be initiated in the calvaria of the rat and rabbit, followed by testing in the mandibles of dogs and monkeys. While calvarial CSDs have been established in the rat, rabbit, and dog, further research is necessary to determine the CSD in the calvaria of the monkey, as well as the mandibles of dogs and monkeys.     

Advances in implantable bionic devices for blindness: a review

Since the 1950s, vision researchers have been working towards the ambitious goal of restoring a functional level of vision to the blind via electrical stimulation of the visual pathways. Groups based in Australia, USA, Germany, France and Japan report progress in the translation of retinal visual prosthetics from the experimental to clinical domains, with two retinal visual prostheses having recently received regulatory approval for clinical use. Regulatory approval for cortical visual prostheses is yet to be obtained; however, several groups report plans to conduct clinical trials in the near future, building upon the seminal clinical studies of Brindley and Dobelle. In this review, we discuss the general principles of visual prostheses employing electrical stimulation of the visual pathways, focusing on the retina and visual cortex as the two most extensively studied stimulation sites. We also discuss the surgical and functional outcomes reported to date for retinal and cortical prostheses, concluding with a brief discussion of novel developments in this field and an outlook for the future.     

The microsystems based visual prosthesis for optic nerve stimulation

The microsystems based visual prosthesis (MiViP) visual prosthesis generates visual perceptions well below safety and stimulator saturation limits. These perceptions, called phosphenes, are of reasonably small size and are broadly distributed in the visual field. They can thus be used to convey useful visual information. Psychophysical evaluations are being performed in order to assess the implantee's benefits in the use of the MiViP optic nerve visual prosthesis. In a pattern-recognition task, the performance improved regularly with practice with an increasing score and a decreasing delay to recognition. These observations open the way toward an evaluation of general mobility improvement with the portable system. In conclusion, the results obtained so far still support the potential usefulness of the optic nerve visual prosthesis. A low-resolution artificial vision can be expected from the prosthesis after extensive training.     

Fetal mouse skin heals scarlessly in a chick chorioallantoic membrane model system

In mammals, the early-gestation fetus has the regenerative ability to heal skin wounds without scar formation. This observation was first reported more than 3 decades ago, and has been confirmed in a number of in vivo animal models. Although an intensive research effort has focused on unraveling the mechanisms underlying scarless fetal wound repair, no suitable model of in vitro fetal skin healing has been developed. In this article, we report a novel model for the study of fetal wound healing. Fetal skin from gestational day 16.5 Balb/c mice (total gestation, 20 days) was grafted onto the chorioallantoic membrane of 12-day-old chicken embryos and cultured for up to 7 days. At 48 hours postengraftment, circular wounds (diameter = 1 mm) were made in the fetal skin using a rotating titanium sapphire laser (N = 45). The tissue was examined daily by visual inspection to look for signs of infection and ischemia. The grafts and the surrounding host tissue were examined histologically. In all fetal skin grafts, the wounds completely reepithelialized by postinjury day 7, with regeneration of the dermis. Fetal mouse skin xenografts transplanted onto the chorioallantoic membrane of fertilized chicken eggs provides a useful model for the study of fetal wound healing. This model can be used as an adjunct to traditional in vivo mammalian models of fetal repair.     

Perceptual learning on an auditory frequency discrimination task by cats: association with changes in primary auditory cortex

The aim of this study was to determine whether auditory perceptual learning is associated with changes in the frequency organization and/or neuronal response properties of primary auditory cortex (AI). Five out of six cats trained on an 8 kHz frequency discrimination task showed improvements in performance that reflected changes in discriminative capacity. Quantitative measures of the response characteristics and frequency organization of AI revealed that the frequency organization of AI in trained cats did not differ from that in controls, but there was a tendency for neurons with a CF immediately above 8 kHz to have slightly broader tuning in the trained cats than in controls, and neurons in one of these bands had significantly shorter latency. These results are in accord with recent reports that cortical topography in primary visual cortex is unchanged in animals trained on visual discrimination tasks, but are at variance with an earlier report of enlarged representations of training frequencies in AI of monkeys trained on a frequency discrimination task. It is concluded that substantial changes in perceptual discriminative capacity can occur without change in primary cortical topography and with only small changes in neuronal response characteristics.     

Murine microvideo endoscopy of the colonic microcirculation

Natural orifice endoscopy in small animal models has been limited in the past by instrument size and optical performance. In this report, we investigate the feasibility of using a recently developed microvideo endoscopy system to evaluate the colon microcirculation. Using a murine model of acute colitis, microvideo endoscopy was useful in mapping the topography of inflammation as well as identifying relevant structures in the microcirculation. We conclude that natural orifice endoscopy is a useful method for the minimally invasive longitudinal assessment of the colonic mucosal microcirculation.     

Receptive fields in human visual cortex mapped with surface electrodes

Most of our understanding of the functional organization of human visual cortex comes from lesion and functional imaging studies and by extrapolation from results obtained by neuroanatomical and neurophysiological studies in nonhuman primates. Although some single-unit and field potential recordings have been made in human visual cortex, none has provided quantitative characterization of spatial receptive fields (RFs) of individual sites. Here we use subdural electrodes implanted for clinical purposes to quantitatively measure response properties in different regions of human visual cortex. We find significant differences in RF size, response latency, and response magnitude for sites in early visual areas, versus sites in later stages of both the dorsal and ventral streams. In addition, we use this technique to estimate the cortical magnification factor in early human visual cortex. The spatial and temporal resolution of cortical surface recordings suggest that this technique is well suited to examine further issues in visual processing in humans.     

Animal models in urinary diversion

We set out to critically assess the value of animal experimentation in urinary diversion through intestinal segments, as some authors question the effectiveness of animal research, criticising the methodological quality, lack of standardization, inadequate reporting and the few systematic reviews in this field. Based on a comprehensive MEDLINE literature search (MeSH database; search terms: urinary diversion, urinary reservoirs, continent, rat, dog, animal models) we retrieved and evaluated all full-length papers published in English, German, French, and Spanish languages from 1966 to 2011 reporting the use of animal models in the setting of urinary diversion. Studies were stratified according to the addressed research question. Within each category species, gender, number of animals, age at procedure, type of diversion, mortality, length of follow-up, experimental procedure and outcome were recorded and tabulated. In all, 159 articles were judged to be relevant and while there are numerous animal models only a few have been used in more than one study. Animals were used for the systematic study of new surgical techniques (93 articles) or metabolic and functional consequences of urinary reconstruction (66 articles). For the latter purpose, the most often used animal is the rat, whereas the dog model is preferred for technical experimentation. In many studies, the validity of the model is at least questionable. Animal experiments have repeatedly been conducted addressing the same question, often with striking discrepancies in outcome. Animal studies were even performed after a surgical technique had been pioneered in humans. The use of animal models in urinary diversion is far from standardized rendering the results less than ideal for comparison across studies. Due to differences in anatomy and physiology, the applicability of findings in animal experiments to clinical urology is limited. Continued effort is needed to optimise the use of animal models in experimental urology.     

人工关节假体感染动物模型的建立

目的 建立更接近临床的模拟人工关节感染的动物模型。方法 以健康成年ＳＤ大鼠为研究对象，在膝关节内置入人的假体表面种植不同剂量的表皮葡萄球菌，通过细菌培养以确定能导致假体感染的稳定细菌剂量。结果 在膝关节内置入假体后，发现致感染的细菌剂量明显小于无假体者，而且置入假体后，能产生细胞外多粘质物质的表皮葡萄球菌ＳＬ－７６亚型致感染的作用，明显强于不能产生ＥＳＳ的表皮葡萄球菌Ｇ２亚型。结论 在金属假体置入     

Über die resorbierbare Gefäßprothese aus Magnesium um 1900

Erwin Payr began to experimentally investigate the issue of vascular anastomosis in 1895. The goal of his research was to develop a reliable and unsophisticated method for reintegrating completely severed blood vessels. For this purpose he employed a resorbable vascular prosthesis made of magnesium. He performed extensive animal testing before he successfully applied his method to a diseased human individual for the first time in 1901. One of his major clinical conclusions for the practice was to absolutely protect the vessel intima from violation due to the risk of local thrombosis. To this end he invented among other things his own vascular forceps.     

Large animal models in fusionless scoliosis correction research: a literature review

Background contextNumerous prenatal, systemic, or local procedures have been described that have created an experimental scoliosis within different animal species. Compression-based fusionless scoliosis correction devices have been used to induce scoliosis (inverse approach) as an indication for their potential corrective efficacy in large animals. Deformities that most closely approximate the three-dimensional nature of an idiopathic-like scoliosis have been created in large animals using a posterior spinal tether. Fusionless scoliosis correction devices have subsequently been tested in these models.PurposeTo provide an overview of large animal models used for preclinical testing of fusionless scoliosis correction devices and to describe recent advances in the creation of an idiopathic-like scoliosis large animal model.Study designLiterature review of large animal models in fusionless scoliosis correction research.MethodsMEDLINE electronic database was searched for studies in which large animal models for spinal or vertebral growth modulation or the creation of an experimental scoliosis were described. The literature search was limited to articles written in the English language.ResultsThe pig appears to be the most suitable animal species for preclinical testing of fusionless scoliosis correction devices because of its large growth potential and the possibility for early weaning. With the inverse approach, it is difficult to gain insight into the possible corrective efficacy of the tested device, and therefore, a two-step approach is preferred. Using a posterior spinal tether, persistent spinal deformities are attained when the deformity has approximately doubled in comparison to the postoperative measure in a time span of approximately 12 weeks. Sufficient tether midline offset is required to render rib procedures unnecessary.ConclusionsAn idiopathic-like scoliosis animal model can be created using a posterior spinal tether in a fully reversible procedure. Experimental results will need to be reproduced to establish a standard idiopathic-like scoliosis large animal model.     

Use and production of biomedical models in the field of audiology

Presently paper mentions the importance that has the use and the production of animal models in scientific research, the relevance that has its use to be able to make a good pursuit in the research, highlighting as well as to facilitate the reproductive of the study in question. Lastly it is mentioned the models more used in the field of the audiology.     

Evaluation of liver support systems for preclinical testing by animal trials

In the present review, various animal models of acute liver failure are reviewed with respect to their suitability for evaluating liver support systems (LSS) according to envisaged modes of therapy. In order to increase the value of the preclinical testing of LSS, it would be advantageous to include more than one animal model in the evaluation program. It is possible to identify appropriate sets of models, which make a suitable test system for particular clinical applications. A standardization of evaluation methods between testing groups would also be beneficial to the field of liver support.     

Retinotopy with coordinates of lateral occipital cortex in humans

OBJECT: The lateral occipital cortex in humans is known as the "extrastriate visual cortex." It is, however, an unexplored field of research, and the anatomical nomenclature for its surface has still not been standardized. This study was designed to investigate whether the lateral occipital cortex in humans has retinotopic representation. METHODS: Four right-handed patients with a diagnosis of intractable epilepsy from space-occupying lesions in the occipital lobe or epilepsy originating in the occipital lobe received permanently implanted subdural electrodes. Electrical cortical stimulation was applied directly applied to the brain through metal electrodes by using a biphasic stimulator. The location of each electrode was measured on a lateral skull x-ray study. Each patient considered a whiteboard with vertical and horizontal median lines. The patient was asked to look at the midpoint on the whiteboard. If a visual hallucination or illusion occurred, the patient recorded its outline, shape, color, location, and motion on white paper one tenth the size of, and with vertical and horizontal median lines similar to those on, the whiteboard. Polar angles and eccentricities of the midpoints of the phosphenes from the coordinate origin were measured on the paper. On stimulation of the lateral occipital lobe, 44 phosphenes occurred. All phosphenes were circular or dotted, with a diameter of approximately 1 cm, except one that was like a curtain in the peripheral end of the upper and lower visual fields on stimulation of the parietooccipital region. All phosphenes appeared in the visual field contralateral to the cerebral hemisphere stimulated. On stimulation of the lateral occipital lobe, 22 phosphenes moved centrifugally or toward a horizontal line. From three-dimensional scatterplots and contour maps of the polar angles and eccentricities in relation to the x-ray coordinates of the electrodes, one can infer that the lateral occipital cortex in humans has retinotopic representation. CONCLUSIONS: The authors found that phosphenes induced by electrical cortical stimulation of the lateral occipital cortex represent retinotopy. From these results one can assert that visual field representation with retinotopic relation exists in the extrastriate visual cortex.     

A power efficient electronic implant for a visual cortical neuroprosthesis

An integrated microstimulator designed for a cortical visual prosthesis is presented, along with a pixel reordering algorithm, together minimizing the peak total current and voltage required for stimulation of large numbers of electrodes at a high rate. In order to maximize the available voltage for stimulation at a given supply voltage for generating biphasic pulses, the device uses monopolar stimulation, where the return electrode voltage is dynamically varied. Thus, the voltage available for stimulation is maximized, as opposed to the conventional fixed return voltage monopolar approach, and impedance is significantly lower than can be achieved using bipolar stimulation with microelectrodes. This enables the use of a low voltage power supply, minimizing power consumption of the device. An important constraint resulting from this stimulation strategy, however, is that current generation needs to be simultaneous and in-phase for all active parallel channels, imposing heavy stress on the wireless power recovery and regulation circuitry in large electrode count systems such as a visual prosthesis. An ordering algorithm to be implemented in the external controller of the prosthesis is then proposed. Based on the data for each frame of the video signal to be transmitted to the implant, the algorithm minimizes the total generated current standard deviation between time multiplexed stimulations by determining the most appropriate combination of parallel stimulation channels to be activated simultaneously. A stimulator prototype has been implemented in CMOS technology and successfully tested. Execution of the external controller reordering algorithm on an application specific hardware architecture has been verified using a System-On-Chip development platform. A near 75% decrease in the total stimulation current standard deviation was observed with a one-pass algorithm, whereas a recursive variation of the algorithm resulted in a greater than 95% decrease of the same variable.     

Experimental model of cisplatin ototoxicity in chinchillas

Cisplatin is an important antineoplastic agent. Its ototoxicity has been well defined, both in human and animal studies. However, animal models of systemic cisplatin administration have been complicated by multiple toxic effects. We studied cisplatin ototoxicity in an animal model involving topical application of cisplatin to the round-window membrane. Adult chinchillas were anesthetized with ketamine and pentobarbital, and auditory function was tested with the use of auditory brain-stem responses to various stimuli (clicks and 8-and 16-kHz tone bursts). Each animal was used as its own control. The middle-ear cavity was exposed through the bulla. In the experimental ear, a 25-μl solution of 0.25 mg cisplatin/1.0 ml normal saline solution was applied to the round-window membrane. In the control ear, 25 μl normal saline solution was applied to the round-window membrane. Follow-up auditory brain-stem response testing was conducted 7 days after treatment. A significant increase in threshold in the experimental ears was seen on comparison with the control ears. This finding suggests that application of cisplatin to the round-window membrane is a useful animal model in which to study cisplatin ototoxicity. (Otolaryngol Head Neck Surg 1998;119:574-80.)