The incidence of volatile anesthesia porcine stress syndrome in pigs (Sus scrofa domesticus) gives implications for physiology during anesthesia

Authors: CORRIGAN, JAMES - Uniformed Services University; MARES, JOHN - Uniformed Services University; HUTZLER, JUSTIN - Uniformed Services University; Nonneman, Danny; BURMEISTER, DAVID - Uniformed Services University

Submitted to: Journal of the American Association for Laboratory Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/25/2024
Publication Date: 1/1/2025
Citation: Corrigan, J., Mares, J.A., Hutzler, J.D., Nonneman, D.J., Burmeister, D.M. 2025. The incidence of volatile anesthesia porcine stress syndrome in pigs (Sus scrofa domesticus) gives implications for physiology during anesthesia. Journal of the American Association for Laboratory Animal Science. 64(1):179-188. https://doi.org/10.30802/aalas-jaalas-24-077.
DOI: https://doi.org/10.30802/aalas-jaalas-24-077

Interpretive Summary: We previously identified a stress-induced condition in swine caused by transport, handling, or isoflurane anesthesia. This condition was caused by a defect variant in the dystrophin gene where mutations cause muscular dystrophy in humans. The dystrophin gene is located on the X chromosome and females usually have a heterozygous genotype and are carriers, and males that have the tryptophan are affected if they receive the affected copy from their dam. In this study we developed a simple PCR/restriction enzyme test and found a high incidence of this dystrophin variant that was associated with detrimental physiological consequences, i.e., elevated creatine kinase and body temperature while under isoflurane anesthesia during surgery. Identifying pigs with this defect could help establish a swine model for Becker Muscular Dystrophy (BMD), which is a milder form of muscular dystrophy compared to the more common and severe Duchenne Muscular Dystrophy (DMD) in humans. Therapies for Muscular Dystrophy commonly involve mitigating the severity of the disease, so studies on BMD are urgently needed. Animal models for DMD exist while animal models for BMD are limited. Additionally, these results indicate that surveillance of biomedical and commercial swine health under stress is important and suggest a need for genetic testing to eliminate these conditions. Furthermore, this study also demonstrates the importance of considering anesthesia choice when performing prolonged porcine studies.

Technical Abstract: Pigs are extensively used for biomedical research as animal models given their similarities to humans including size, arterial capacity, and cutaneous structure. While their size also allows for the use of clinically available anesthesia equipment (for example, endotracheal tubes and ventilators), anecdotes exist with respect to stress reactions after exposure to volatile anesthetics. Over 3 mo at our institution, 11 pigs (Sus scrofa domesticus) exposed to isoflurane anesthesia during 2 research protocols were euthanized after exhibiting clinical signs of malignant hyperthermia, including hyperthermia, hypercapnia, skeletal muscle rigidity, dyspnea, tachycardia, and hypotension. This group was composed of intact Yorkshire/Landrace crosses (68 to 91 kg) purchased from a research breeder. While malignant hyperthermia is caused by a mutation in ryanodine receptor 1 (RYR1), another unnamed porcine stress syndrome is caused by a dystrophin defect. We analyzed the incidence of the RYR1 mutation and a dystrophin variant in 9 of the originally clinically affected pigs and in 56 subsequent pigs. All animals tested negative for the RYR1 mutation, while the dystrophin variant was found in 2 out of 7 clinical (28.6%) and 22 out of 46 (47.8%) subsequently tested female pigs. Creatine kinase, indicative of muscle damage, was slightly elevated at baseline in dystrophin variant-positive carriers, albeit not significantly. However, for the original clinically affected pigs, the increase in body temperature while under anesthesia was significantly greater in dystrophin variant-positive carriers (7.9 ± 0.8 °C) compared with noncarriers (5.2 ± 0.6 °C, P = 0.046). Taken together, we describe the suspected involvement of a dystrophin variant as one of the genetic etiologies in an unnamed condition that has been anecdotally experienced by pig researchers but not reported. We propose naming this condition volatile anesthesia porcine stress syndrome (VAPSS), which is an umbrella term that includes multiple genetic origins, the most well-known of which is malignant hyperthermia stress syndrome in pigs. Identifying other etiologies for VAPSS has implications for genetic and clinical screening to improve welfare in pigs bred for biomedical research and agricultural purposes.