The Incidence of Volatile Anesthesia Porcine Stress Syndrome in Pigs (Sus scrofa domesticus) Gives Implications for Physiology during Anesthesia.

James Corrigan, John Mares, Justin Hutzler, Dan Nonneman, David M Burmeister
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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.

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猪(Sus scrofa domesticus)挥发性麻醉猪应激综合征的发生率在麻醉期间的生理学意义。
猪被广泛用于生物医学研究作为动物模型,因为它们与人类相似,包括大小、动脉容量和皮肤结构。虽然它们的大小也允许使用临床可用的麻醉设备(例如,气管内管和呼吸机),但关于暴露于挥发性麻醉剂后的应激反应存在轶事。在我们机构的3个多月里,11头猪(Sus scrofa domesticus)在2个研究方案中暴露于异氟醚麻醉,在出现恶性高热的临床症状后被安乐死,包括高热、高碳酸血症、骨骼肌僵硬、呼吸困难、心动过速和低血压。该组由从研究育种者处购买的完整的约克郡/长白杂交(68至91公斤)组成。恶性高热是由ryanodine受体1 (RYR1)突变引起的,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RYR1突变和肌营养不良蛋白变异在9头最初临床感染的猪和56头随后感染的猪中的发病率。所有动物的RYR1突变检测均为阴性,而7头临床猪中有2头(28.6%)和46头随后检测的母猪中有22头(47.8%)发现了肌营养不良蛋白变异。肌酸激酶是肌损伤的指示指标,在肌营养不良蛋白变异阳性携带者中,肌酸激酶在基线水平上略有升高,但并不显著。然而,对于最初的临床感染猪,麻醉时,肌营养不良蛋白变异阳性携带者(7.9±0.8°C)的体温升高明显高于非携带者(5.2±0.6°C, P = 0.046)。综上所述,我们将一种肌营养不良蛋白变异的疑似参与描述为一种未命名条件下的遗传病因之一,这种情况已经由猪研究人员趣闻性地经历过,但尚未报道。我们建议将这种情况命名为挥发性麻醉猪应激综合征(VAPSS),这是一个包含多种遗传起源的总称,其中最著名的是猪的恶性高温应激综合征。确定VAPSS的其他病因对遗传和临床筛选具有重要意义,可以提高用于生物医学研究和农业目的的猪的福利。
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