rate—can greatly facilitate the monitoring of anesthesia and general physiologic state (Vogler, 1997). However, not all devices maintain a historical record, and regular measurements should be recorded under these circumstances. The use of automated devices cannot substitute for direct monitoring of the animal by a human observer (see also Mason and Brown, 1997), and a human observer should be present at all times during a prolonged nonsurvival procedure, as the clinical status of the animal can change quickly and require intervention. Monitoring data should be filed by experiment and animal and kept for at least the duration of the overall project (NIH, 1986). The issues involved in maintaining an experimental animal in good physiologic condition during a prolonged recording experiment are similar to those involved in other situations that require the long-term maintenance of animals in clinical situations (NIH, 1991). Animals that are paralyzed must be ventilated artificially, and standard veterinary practices should be followed when selecting the gas mixture and anesthetic or analgesic used (Vogler, 1997). In some cases, gaseous anesthetics or analgesics are included in the gas mixture (such as isoflurane and N2O), while in other cases, room air with or without added oxygen is used. The use of a mixture of 50% O2 and 50% N2O may be helpful, in that N2O potentiates intravenous anesthetics (NIH, 1991). However, N2O increases cerebral blood flow, and this side effect may be of special concern to researchers performing intracranial procedures (Drummond et al., 1987). Animals exposed to artificial ventilation for long periods should be hyperinflated (sighed) at regular intervals to help to avoid collapse of the pulmonary alveoli (atelectasis) (Vogler, 1997). Hydration of the inspired gases is also helpful in preventing desiccation of lung tissues. That can be accomplished by passing the air through fluid in a flow-through system or by using a closed-loop system that obviates additional hydration; passive humidification devices are also effective, inexpensive, and appropriate for multi-day use. A straightforward way of monitoring the adequacy of
OCR for page 92
artificial ventilation is to measure end-tidal CO2 either continuously or at frequent intervals (Vogler, 1997). Animals are typically given an osmotically balanced fluid and metabolites, such as lactated Ringers solution with dextrose, intravenously (DiBartola, 2000; Haskins and Eisele, 1997). When data collection goes on for several days, supplementation of that solution with potassium and/or amino acids may be desirable. For shorter experiments (under 48 hours), periodic subcutaneous administration of fluid may be sufficient. In all cases, the total volume administered should be adequate to make up for what is lost through the skin and lungs and should be sufficient to maintain renal function. The role of the kidneys in maintaining pH and osmotic balance is critical, and normal renal function can be particularly important in preventing the imbalances that may occur when animals are subjected to prolonged artificial ventilation. Monitoring urine output may be helpful in some situations to ensuring adequate renal function and hydration. During long experiments, rearranging an animal’s limbs and body and massaging the large muscle masses regularly can help to prevent the edema and venous pooling that occur in the absence of muscle tone and movement. Providing regular doses of antibiotics, vitamins, and anti-inflammatory agents may help to keep an animal in a stable condition and prevent infection (NIH, 1991). Core body temperature should be monitored throughout the period of paralysis, and supplemental heat should be provided as needed with forced air or circulating water heating pads (e.g., Vogler, 1997). Evaluating the need for aseptic technique in prolonged nonsurvival experiments requires the professional judgment of the investigator, veterinarian, and IACUC case by case. In general, the need for asepsis will depend on the duration of the experiment and the extent