Corrigan James, Mares John, Hutzler Justin, Nonneman Dan, Burmeister David M
1Department of Laboratory Animal Resources, Uniformed Services University, Bethesda, Maryland.
2Department of Preventive Medicine and Biostatistics, Uniformed Services University, Bethesda, Maryland.
J Am Assoc Lab Anim Sci. 2025 Jan 1;64(1):179-188. doi: 10.30802/AALAS-JAALAS-24-077.
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.
猪因其在体型、动脉容量和皮肤结构等方面与人类相似,被广泛用作生物医学研究的动物模型。虽然它们的体型也使得能够使用临床可用的麻醉设备(例如气管内插管和呼吸机),但关于接触挥发性麻醉剂后的应激反应也有一些传闻。在我们机构的3个多月时间里,11头猪(家猪)在2项研究方案中接受异氟烷麻醉后,出现恶性高热的临床症状(包括体温过高、高碳酸血症、骨骼肌僵硬、呼吸困难、心动过速和低血压),随后被安乐死。这组猪由从一家研究种猪场购买的纯种约克夏/长白杂交猪(68至91千克)组成。虽然恶性高热是由兰尼碱受体1(RYR1)的突变引起的,但另一种未命名的猪应激综合征是由肌营养不良蛋白缺陷引起的。我们分析了最初临床受影响的9头猪和随后56头猪中RYR1突变和肌营养不良蛋白变体的发生率。所有动物的RYR1突变检测均为阴性,而在随后检测的7头临床猪中有2头(28.6%)以及46头雌性猪中有22头(47.8%)发现了肌营养不良蛋白变体。肌酸激酶是肌肉损伤的指标,在肌营养不良蛋白变体阳性携带者中,其基线水平略有升高,尽管不显著。然而,对于最初临床受影响的猪,与非携带者(5.2±0.6℃,P = 0.046)相比,肌营养不良蛋白变体阳性携带者在麻醉期间体温升高幅度明显更大(7.9±0.8℃)。综上所述,我们描述了肌营养不良蛋白变体作为一种未命名病症的遗传病因之一的疑似情况,这种情况猪研究人员曾有传闻但未报告。我们建议将这种病症命名为挥发性麻醉猪应激综合征(VAPSS),这是一个涵盖多种遗传起源的统称,其中最广为人知的是猪的恶性高热应激综合征。确定VAPSS的其他病因对于遗传和临床筛查具有重要意义,有助于改善用于生物医学研究和农业目的的猪的福利。