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Disproportional cardiovascular depressive effects of isoflurane: Serendipitous findings from a comprehensive re-visit in mice
Lab Animal ( IF 6.9 ) Pub Date : 2020-11-30 , DOI: 10.1038/s41684-020-00684-w
Yan-Yuen Poon , Ching-Yi Tsai , Ya‐Hui Huang , Jacqueline C. C. Wu , Samuel H. H. Chan , Julie Y. H. Chan

Employment of anesthetics, including isoflurane, though mandatory in animal experiments, is often regarded as a major limitation because results obtained with anesthetics may be different from those obtained under a conscious state. This study re-visits two issues related to the use of isoflurane. First, does isoflurane exert depression equally on all aspects of cardiovascular functions and their regulations? Second, is the circulatory supply of oxygen to brain tissues sufficient under isoflurane anesthesia? We determined in male C57BL/6J mice the temporal effects of 1.5% (vol/vol) isoflurane on blood pressure (BP), heart rate (HR), cardiac performance, baroreflex-mediated sympathetic vasomotor tone, cardiac vagal baroreflex, functional connectivity within the baroreflex neural circuits, carotid or cerebral blood flow, cortical tissue oxygen level, respiratory rate and blood gas. Over 150 min after exposure to 1.5% isoflurane, BP and HR were sustained at 71% and 79% of their awake levels amid a trend of progressive increase. Cardiac performance was within physiological ranges. Baroreflex-mediated sympathetic vasomotor tone gradually reversed from an 85% reduction toward the conscious level, alongside a parallel decrease in inhibitory connectivity between nucleus tractus solitarii (NTS) and rostral ventrolateral medulla. A decline in excitatory connectivity between NTS and nucleus ambiguus accompanied the decrease in cardiac vagal baroreflex. There were progressive increases in carotid or cerebral blood flow and tissue oxygen tension in cerebral cortex, alongside gradual hypoventilation, mild respiratory acidosis and hypercapnia. We conclude that, by eliciting disproportional depressive actions on cardiovascular functions and their regulations, which sustain circulatory supply of oxygen to brain tissues, 1.5% isoflurane is sufficient to maintain optimal cardiovascular functions in mice.



中文翻译:

异氟醚的心血管抑制作用不成比例:从小鼠的全面研究中意外发现

尽管在动物实验中必须使用麻醉剂,包括异氟烷,但通常被视为主要限制,因为使用麻醉剂获得的结果可能与有意识状态下获得的结果不同。这项研究重新探讨了与异氟烷的使用有关的两个问题。首先,异氟烷是否会在心血管功能及其调节的各个方面平等地产生抑郁感?第二,在异氟烷麻醉下,脑组织的循环氧气供应是否充足?我们在雄性C57BL / 6J小鼠中确定了1.5%(vol / vol)异氟烷对血压(BP),心率(HR),心脏性能,压力反射介导的交感性血管舒缩,心脏迷走神经压力反射,内在功能连接的时间影响压力反射神经回路,颈动脉或脑血流量,皮质组织氧水平,呼吸频率和血气。暴露于1.5%的异氟烷​​后150分钟内,BP和HR持续保持其清醒水平的71%和79%,呈逐渐增加的趋势。心脏表现在生理范围内。Baroreflex介导的交感性血管舒缩逐渐从85%的降低向意识水平逆转,同时孤束核(NTS)和延髓腹侧延髓之间的抑制连接性平行降低。NTS和歧核之间的兴奋性连接性下降伴随着心脏迷走神经压力反射的减少。随着逐渐换气不足,轻度呼吸性酸中毒和高碳酸血症,大脑皮质的颈动脉或脑血流量和组织氧张力逐渐升高。我们得出结论,

更新日期:2020-12-01
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