Effects of Long-term Anesthesia, Blood Sampling, Transportation, and Infection Status on Hearts and Brains in Pigs Inoculated with Staphylococcus aureus and Used for Imaging Studies.

Laboratory animals are widely used in imaging studies, including infection, heart, and brain research. Compared with rodents, pigs are especially useful because of their large organ sizes, ability to tolerate long-term anesthesia, and substantial blood volume, which allows repeated blood sampling. These factors are particularly important in positron emission tomography studies of potential new radioactive tracers, because the scans often are prolonged; in addition, kinetic studies involving repeated blood sampling may be performed to establish the optimal scan time. However, protracted studies may affect the cardiovascular system, brain, and other organs. This raises the question of how to monitor and counteract the effects of longterm anesthesia in pigs in a typical experimental setting yet prevent introducing bias into the experiment. To address this question, we investigated the effects of long-term anesthesia (maximum, 18 h), repeated blood sampling (maximum of 20 mL blood per kilogram body weight), and road transportation (as long as 1.5 h between 2 imaging centers) on key variables of lung, heart, and brain function in the context of a well-established pig model of Staphylococcus aureus infection. Pulse rate, oxygen saturation, body temperature, arterial pressure of CO2, and urine production were stable during anesthesia for at least 16 h, whereas blood glucose slowly decreased. Hct and leukocyte count decreased due to repeated blood sampling. During road transportation, blood lactate levels increased 5 fold and arterial pressure of O2 decreased by 50%. Repeated CT scans, necropsy results, and histopathology findings documented progressive lung changes and acute cardiac necrosis. No lesions indicative of hypoxia were found in brain. The study data show that the typical monitoring parameters do not fully depict the cardiovascular state of pigs during prolonged anesthesia. We recommend streamlining experimental protocols for imaging studies in pigs to avoid organ pathology.

Pigment Deposition in the Rat Retina.

Incidental findings in the rat eye are not uncommon in acute and long-term toxicological studies. These findings can be associated with a number of causes unrelated to treatment with the test article, including congenital malformation, trauma, infection, metabolic disease, genetic predisposition, and age-related changes. The occurrence of pigment deposition in the retina of Wistar Hannover (Crl:WI (Han)) rats in a 4-week toxicity study is reported in this communication. The microscopic examination of the eyes in the 4-week toxicity study revealed focal yellow-brown pigment deposits in the retina, mainly located in the ganglion cell layer. The retinal pigment deposits were randomly distributed in the control and treated groups and were considered incidental. The deposits were clearly positive for ferric iron in the Perls' stain but not for lipofuscin by the Schmorl's and Long Ziehl-Neelsen methods. The iron-containing pigment is likely to represent hemosiderin accumulation after retinal micro-hemorrhage or could be indicative of the normal intraretinal iron transport and turnover.