Reported analgesic administration to rabbits undergoing experimental surgical procedures.

BACKGROUND: It has become widely accepted that whenever animals are used in scientific procedures, the 3Rs principle of replacement, reduction and refinement described by William Russell and Rex Burch should be adhered to. Animals should be replaced with non-sentient alternatives if possible, the number of animals used should be reduced and experimental procedures should be refined to minimise pain, suffering and distress. Administration of analgesic agents to animals undergoing surgical procedures is a refinement used to alleviate pain. In this study, a structured literature review was carried out to examine current trends in analgesic administration to rabbits undergoing experimental surgical procedures. RESULTS: 128 papers from 51 peer-reviewed journals were selected for inclusion in this review. Reporting administration of systemic analgesia to rabbits in peer-reviewed scientific papers increased significantly from 16% to 50% between 1995-1997 and 2005-2007 (P < 0.001). Papers that reported ethical approval were more likely than papers that did not specify approval to report systemic analgesic administration (P < 0.001). When systemic analgesics were administered, buprenorphine was the most frequently used agent and non-steroidal anti-inflammatory drugs were used less frequently than opioids in both time periods. CONCLUSIONS: Although this review provides evidence that systemic analgesic administration to rabbits undergoing surgical procedures is increasing, rabbits do not always receive analgesia when they undergo experimental surgery. Other practices in rabbit perioperative care that could be improved, highlighted by this survey include: 1) changing the timing of analgesic administration by giving systemic analgesics pre- or perioperatively rather than only postoperatively, 2) using multimodal analgesia when pain is likely to be moderate to severe and 3) increasing the use of non-steroidal anti-inflammatory drugs and use of other techniques such as epidural analgesia particularly for orthopaedic procedures.

Reported analgesic administration to rabbits, pigs, sheep, dogs and non-human primates undergoing experimental surgical procedures.

Reported analgesic use following experimental surgery is low in rodents and there has been little published information on the frequency of analgesic use in other laboratory species. A structured literature review was conducted to examine analgesic administration in larger laboratory animals. The Scirus search engine was used to identify studies published in peer-reviewed journals that reported carrying out experimental surgery on 'large' laboratory animals, specifically rabbits, pigs, sheep, dogs and non-human primates. Seventy-four studies between 2000 and 2001 and 75 studies between 2005 and 2006 were included in the review. There was an increase in the reported administration of systemic analgesics to these species from 50% in 2000-2001 to 63% in 2005-2006. When all agents with analgesic properties were considered (systemic analgesics, local anaesthetics and anaesthetics with analgesic components), the proportion of papers that reported some form of analgesic administration to 'large' laboratory animals increased from 86% in 2000-2001 to 89% in 2005-2006. Overall rabbits, pigs, sheep, dogs and non-human primates were more likely to receive analgesics following potentially painful experimental procedures than has been reported in laboratory rodents but analgesic administration to 'large' laboratory species is still not optimal.

Reported analgesic and anaesthetic administration to rodents undergoing experimental surgical procedures.

A structured literature review was carried out to assess recent trends in the administration of analgesics and anaesthetics to laboratory rats and mice undergoing surgical procedures. The ScienceDirect database was used to systematically identify studies published in peer-reviewed journals over two periods (2000-2001 and 2005-2006), 86 studies from each time period were included in the review. The total number of animals that underwent surgery, species used, type of procedure, anaesthetic regimen and analgesic administration were noted for each study. There was an increase in the reported administration of systemic analgesics from 10% in 2000-2001 to 20% in 2005-2006. Buprenorphine was the most commonly reported analgesic in both periods (2000-2001: 78%, 2005-2006: 35%) and reporting the use of non-steroidal anti-inflammatory drugs increased from 11% to 53%. There was also a change in reported anaesthetic practices, notably a decrease in the use of pentobarbital and an increase in the use of isoflurane and ketamine/xylazine. Although reported administration of analgesics has increased and there has been some refinement in the selection of anaesthetic agents used, the findings of this review suggest that there is still significant scope for improvement with respect to the perioperative care of laboratory rodents.

Development of electronic learning courses for surgical training of animal research personnel.

The animal research community comprises members from a wide variety of backgrounds, some of whom must learn basic surgical skills. Though demand for animal research personnel who have surgical skills is increasing, surgical training opportunities are becoming more scarce. Electronic learning or e-learning platforms can be used as an adjunct to hands-on surgical training. Course developers can adapt these e-learning courses to fit the needs of participants who have varying levels of expertise. The authors outline the steps involved in developing an effective e-learning surgical course. They also describe how to use various equipment and software products to help implement e-learning courses. Though the authors focus on developing surgical courses, course developers could apply the general steps outlined by the authors when developing any e-learning course.

An introduction to electronic learning and its use to address challenges in surgical training.

The animal research community faces a shortage of surgical training opportunities along with an increasing demand for expertise in surgical techniques. One possible means of overcoming this challenge is the use of computer-based or electronic learning (e-learning) to disseminate material to a broad range of animal users. E-learning platforms can take many different forms, ranging from simple text documents that are posted online to complex virtual courses that incorporate dynamic video or audio content and in which students and instructors can interact in real time. The authors present an overview of e-learning and discuss its potential benefits as a supplement to hands-on rodent surgical training. They also discuss a few basic considerations in developing and implementing electronic courses.

Anesthetic experimental device for small animal.

PURPOSE: The difficulty to anesthetize small laboratory animals with vaporizer prompted us to go in search of new materials, and create new techniques. The improved equipment of anesthesia we looked for should be low cost, practical, versatile, and its management serve ethical, teaching, and research purposes. METHODS: The new components of the equipment were: the vaporizer, the unidirectional valve, the glass cylinder filled with water, the flow guidance y-shape tube, the flow regulators, the mask modifications, and another free airway for emergency occurrence. A test was done with 30 Wistar rats, Rattus norvegicus albinus, divided into three groups with 10 rats for each one. Groups 1, 2 and 3 were anesthetized with Ether, Halothane and Sevoflurane respectively, using the new gadget. The anesthetic induction time, the breathing rhythm alteration during an anesthesia pre-established time (10 minutes), and the recovery time were observed. RESULTS: The equipment enabled an easy handling, and fulfilled a larger safeness and stability during the induction and anesthetic management. The test showed it was possible to make use of several anesthetic agents. CONCLUSION: The device is effective, and turns the anesthesia procedure into a very easy practice with low-cost. It should be recommended for experimental surgery, teaching and research.

Clinical protocol levels are required in laboratory animal surgery when using medical devices: experiences with ureteral replacement surgery in goats.

It is common to test medical devices in large animal studies that are or could also be used in humans. In this short report we describe the use of a ureteral J-stent for the evaluation of biodegradable tubular constructs for tissue reconstruction, and the regeneration of ureters in Saanen goats. Similarly to a previous study in pigs, the ureteral J-stent was blindly inserted until some resistance was met. During evaluation of the goats after three months, perforation of the renal cortex by the stent was observed in four out of seven animals. These results indicated that blind stent placement was not possible in goats. In four new goats, clinical protocols were followed using X-ray and iodinated contrast fluids to visualize the kidney and stent during stent placement. With this adaptation the stents were successfully placed in the kidneys of these four new goats with minimal additional effort. It is likely that other groups in other fields ran into similar problems that could have been avoided by following clinical protocols. Therefore, we would like to stress the importance of following clinical protocols when using medical devices in animals to prevent unnecessary suffering and to reduce the number of animals needed.

Intraoral cheek fistulae: a refined technique.

Taste reactivity testing (TRT), which entails infusing a solution into the oral cavity of subjects, is used across a wide range of studies. For laboratories inexperienced in the conventional technique of implanting cheek fistulae, the surgery can be problematic for both the subjects and the experimenter. We have proposed a refined method for fistulae implantation that is less invasive, thereby reducing the pain and distress of the animals. Using this refined technique, we were able to replicate the findings of previous TRT studies, namely that a high dose of lithium chloride produces an increase in aversive and a decrease in ingestive orofacial and somatic responses. Using indices of health, we demonstrate that unlike animals with the conventional method of fistulae implantation, subjects that receive the refined technique regain their pre-surgery body weights rapidly and show no physical signs of discomfort. Additional advantages of the refined technique are discussed.

The impact of different blood sampling methods on laboratory rats under different types of anaesthesia.

Rats with implanted telemetry transponders were blood sampled by jugular puncture, periorbital puncture or tail vein puncture, or sampled by jugular puncture in carbon dioxide (CO2), isoflurane or without anaesthesia in a crossover design. Heart rate, blood pressure and body temperature were registered for three days after sampling. Initially blood pressure increased, but shortly after sampling it decreased, which led to increased heart rate. Sampling induced rapid fluctuations in body temperature, and an increase in body temperature. Generally, rats recovered from sampling within 2-3 h, except for rats sampled from the tail vein, which showed fluctuations in body temperature in excess of 30 h after sampling. Increases in heart rate and blood pressure within the first hours after sampling indicated that periorbital puncture was the method that had the largest acute impact on the rats and that it might take an extra hour to recover from it. CO2 anaesthesia seemed unable to prevent the increase in blood pressure and the fluctuations in body temperature induced by blood sampling, and up to 10 h after sampling, the rats were still affected by CO2 anaesthesia. Rats anaesthetized with isoflurane showed lower increases in blood pressure after, and fewer fluctuations in body temperature during sampling, and the post-anaesthetic effects of isoflurane, if any, seemed to disappear immediately after sampling. It is, therefore, concluded that blood sampling in rats by jugular puncture seems to be the method from which rats most rapidly recover when compared with periorbital puncture and tail vein puncture, and that for anaesthesia, isoflurane is recommended in preference to CO2.

Transfusion via the carotid artery in the hamster.

Public health policy makers need quantitative scientific data to assess the risk to the blood supply posed by transmissible spongiform encephalopathy (TSE) diseases. To this end, our laboratory has developed a model of blood-borne TSE infectivity in hamsters infected with the 263K strain of scrapie, an experimental model of choice for quantitative studies of TSE infectivity. We report here a microsurgical method for cannulation of the carotid artery in the hamster that allows transfusion of a large fraction of the blood volume of the hamster, with virtually no blood loss to the surgical site or exposure to nervous tissue. Animals are minimally affected by the surgery, recover quickly and completely, and survive for their natural lives (as long as 3 years). This procedure has been used to obtain quantitative data on the transmissibility of the TSEs by transfusion, and these findings have informed public health policy on blood donation and blood use.

Thyroparathyroidectomy procedures and thyroxine levels in the chinchilla.

Thyroid and embedded parathyroid glands were surgically removed (thyroparathyroidectomized) from adult chinchillas (Chinchilla laniger) to create an animal model of hypothyroidism. Thyroxine (T4) levels were measured at the time of surgery and one or two times after surgery from 10 thyroparathyroidectomized chinchillas and five sham controls to establish baseline serum T4 levels and to assess the degree and duration of hypothyroidism in this animal model. Baseline T4 levels ranged from 3.4 to 6.4 microg/dl (mean +/- 1 standard deviation, 5.25 +/- 0.84 microg/dl), with no differences between male and female chinchillas (5.4 +/- 0.6 microg/dl versus 5.2 +/- 1.0 microg/dl, respectively). T4 levels were significantly reduced in 80% of thyroparathyroidectomized chinchillas when measured 6 to 14 days after surgery, but reductions were variable, ranging from 9 to 89% in individual animals. There was rapid regrowth of thyroid tissue and a return of T4 levels to the baseline range in five of the seven animals followed for 1 to 2 months after surgery. T4 levels increased significantly in the sham-operated chinchillas, indicating a nonspecific effect of surgery. The results establish surgical procedures for creating a model of variable, transient hypothyroidism in the chinchilla. We also summarize published basal T4 values for various laboratory animals, to provide a convenient reference.

Surgery in fish research: common procedures and postoperative care.

As the use of fish models in biomedical research increases, so too does the need for individuals working in laboratory animal science to be familiar with surgical procedures in these animals. The author presents a primer on fish surgery with an emphasis on research applications.

A study of VitalView for behavioural and physiological monitoring in laboratory rats.

We describe the use of a commercially available telemetry and data acquisition system to record heart rate, body temperature and activity of freely behaving rats with transmitters that operate without batteries (transponders). The system uses PDT 4000HR E-Mitters (Mini Mitter, OR, USA) to acquire animal temperature, heart rate and motor activity data. E-Mitters obtain power from a radiofrequency field produced by an ER-4000 energizer/receiver so that transponders can collect data on heart rate, body temperature and gross motor activity. ER-4000 energizers/receivers are designed to be placed below the animals' cage. Data output from receivers is managed by a Windows PC-based data acquisition system, VitalView. In this study, we report that a good correlation exists between VitalView and Powerlab for the determination of heart rate and between intra-abdominal (telemetric) and colonic body temperature (rectal digital thermometer) in rats. Assessment of this system by using agents that have well-documented effects on heart rate, body temperature and locomotor activity have also been determined. An additional feature of VitalView is the incorporation of behavioural inputs (feeding monitors to monitor duration and frequency of feeding and a lickometer to monitor drinking bouts) into the data acquisition system designed primarily to acquire data from the implanted transponders. Circadian rhythms for all parameters were established in rats with E-Mitters implanted. VitalView may be used for the determination of multiple parameters in freely behaving animals using transponders, which operate without batteries. This capability is unique in its field and represents a recent advance in biotelemetric monitoring of laboratory animals.

Guidelines for training in surgical research in animals, Academy of Surgical Research, April 1989.

This document is not meant to be a regulatory statement but rather to be utilized as a guideline for research institutions who are trying to adhere to the training regulations detailed by various governmental agencies. It is our hope that institutions and individuals will take a proactive stance in requiring adequate training and experience for persons performing experimental surgery on laboratory animals. Only by adherence to voluntary standards that ensure humane care and use of laboratory animals in research can we expect to avoid more stringent laws and regulations. More importantly, by adhering to these voluntary standards the quality of animal research can be improved, which should result in more effective and efficient use of our resources.