Department of Pharmacology, Addiction Science and Toxicology, College of Medicine, The University of Tennessee Health Science Center, 71 S. Manassas, Memphis, TN, 38103, USA.
Laboratory Animal Care Unit, The University of Tennessee Health Science Center, Memphis, TN, 38103, USA.
BMC Anesthesiol. 2023 Dec 12;23(1):411. doi: 10.1186/s12871-023-02320-9.
Ethyl alcohol and cannabis are widely used recreational substances with distinct effects on the brain. These drugs increase accidental injuries requiring treatment under anesthesia. Moreover, alcohol and cannabis are often used in anesthetized rodents for biomedical research. Here, we compared the influence of commonly used forms of anesthesia, injectable ketamine/xylazine (KX) versus inhalant isoflurane, on alcohol- and (-)-trans-delta9-tetrahydrocannabinol (THC) effects on cerebral arteriole diameter evaluated in vivo.
Studies were performed on male and female Sprague-Dawley rats subjected to intracarotid catheter placement for drug infusion, and cranial window surgery for monitoring pial arteriole diameter. Depth of anesthesia was monitored every 10-15 min by toe-pinch. Under KX, the number of toe-pinch responders was maximal after the first dose of anesthesia and diminished over time in both males and females. In contrast, the number of toe-pinch responders under isoflurane slowly raised over time, leading to increase in isoflurane percentage until deep anesthesia was re-established. Rectal temperature under KX remained stable in males while dropping in females. As expected for gaseous anesthesia, both males and females exhibited rectal temperature drops under isoflurane.
Infusion of 50 mM alcohol (ethanol, EtOH) into the cerebral circulation rendered robust constriction in males under KX anesthesia, this alcohol action being significantly smaller, but still present under isoflurane anesthesia. In females, EtOH did not cause measurable changes in pial arteriole diameter regardless of the anesthetic. These findings indicate a strong sex bias with regards to EtOH induced vasoconstriction. Infusion of 42 nM THC in males and females under isoflurane tended to constrict cerebral arterioles in both males and females when compared to isovolumic infusion of THC vehicle (dimethyl sulfoxide in saline). Moreover, THC-driven changes in arteriole diameter significantly differed in magnitude depending on the anesthetic used. Simultaneous administration of 50 mM alcohol and 42 nM THC to males constricted cerebral arterioles regardless of the anesthetic used. In females, constriction by the combined drugs was also observed, with limited influence by anesthetic presence.
We demonstrate that two commonly used anesthetic formulations differentially influence the level of vasoconstriction caused by alcohol and THC actions in cerebral arterioles.
乙醇和大麻是广泛使用的娱乐性物质，对大脑有明显的影响。这些药物会增加需要在麻醉下治疗的意外伤害。此外，酒精和大麻通常用于麻醉啮齿动物进行生物医学研究。在这里，我们比较了常用的麻醉形式，即注射用氯胺酮/二甲苯胺（KX）与吸入异氟烷，对体内评估的乙醇和（-）-反式-9-四氢大麻酚（THC）对脑小动脉直径的影响。
研究对象为雄性和雌性 Sprague-Dawley 大鼠，它们接受颈内导管放置以进行药物输注，并接受颅窗手术以监测软脑膜小动脉直径。每隔 10-15 分钟通过脚趾捏合监测麻醉深度。在 KX 下，雄性和雌性动物在第一次麻醉后，脚趾捏合的反应者数量最多，并随时间逐渐减少。相比之下，在异氟烷下，脚趾捏合的反应者数量随着时间的推移缓慢增加，导致异氟烷百分比增加，直到重新建立深度麻醉。雄性动物的直肠温度在 KX 下保持稳定，而雌性动物的直肠温度下降。正如气态麻醉所预期的那样，雄性和雌性动物在异氟烷下都出现直肠温度下降。
在 KX 麻醉下，将 50mM 乙醇（乙醇）输注到脑循环中，导致雄性动物的小动脉强烈收缩，这种乙醇作用明显较小，但在异氟烷麻醉下仍存在。在雌性动物中，无论使用哪种麻醉剂，乙醇都不会导致软脑膜小动脉直径发生可测量的变化。这些发现表明，乙醇诱导的血管收缩与性别有很强的偏倚。在雄性和雌性动物中，与等容输注 THC 载体（二甲亚砜在盐水中）相比，在异氟烷下输注 42nM THC 往往会使脑小动脉收缩。此外，动脉直径的 THC 驱动变化的幅度在很大程度上取决于所使用的麻醉剂。同时给予雄性动物 50mM 乙醇和 42nM THC，无论使用哪种麻醉剂，都会使脑小动脉收缩。在雌性动物中，联合药物的收缩也观察到了，但麻醉剂的存在影响有限。
我们证明了两种常用的麻醉配方会以不同的方式影响乙醇和 THC 作用在脑小动脉中引起的血管收缩程度。
