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

Abstract

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.

siRNA-mediated reduction of a circulating protein in swine using lipid nanoparticles

“…The anesthesia protocol, premedication, and intravenous infusion protocol may have contributed to mild organ toxicity 88 , 89 , 90 in both the siPLG and PBS groups, as transient increases were observed in creatine kinase and BUN levels, respectively, and transient decreases were observed in total protein levels. However, general anesthesia is commonly utilized during serial blood sampling in swine 91 and in other large animals such as NHPs. 92 Albumin levels in the siPLG group were reduced at 5 h compared to the control groups, which could be attributed to the mild and transient liver toxicity in these animals, as the liver is the site of albumin synthesis.…”

Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

“…Thus, pig models have a high construct validity. Pigs can be anesthetized for many hours [ 10 ], which combined with the size of pigs, allows for serial blood sampling [ 15 ]. This makes pigs attractive models for kinetic imaging studies.…”

“…Our studies used a range of tracers in each animal. However, even though pigs can be kept anesthetized for many hours, intense blood sampling (>20 mL/kg) also affected the pigs’ physiology, with an effect on circulation and lung function [ 10 ].…”

“…During our experiments, we obtained new knowledge on how to use our model. This resulted in a better and more robust model [ 8 , 9 , 10 ]. In the present review, we will generalize our experience and put it into a broader context.…”

Comparison of two injectable anaesthetic techniques on induction and subsequent anaesthesia in pigs

“…In these studies, anaesthesia of the animal is usually required, and long-term anaesthesia is often needed. 1 The effects of anaesthetic and analgesic drugs differ between species 2 and may cause physiological changes, 3 thus possibly affecting the outcome and results of the research. 4 Pigs are easily stressed during their handling before anaesthesia is induced, which can interfere with the onset of action of the drugs targeting the central nervous system.…”