Ding Xueqin, Murray Paul A
Center for Anesthesiology Research, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Anesth Analg. 2007 Nov;105(5):1278-86, table of contents. doi: 10.1213/01.ane.0000281118.19745.70.
Pulmonary venous contraction can increase pulmonary capillary pressure and pulmonary edema. In the present study, we investigated the direct effects of ketamine, etomidate, thiopental, and midazolam on pulmonary venous contraction and myofilament Ca2+ sensitivity in permeabilized pulmonary venous smooth muscle (PVSM).
The effects of these IV anesthetics on acetylcholine contraction were assessed in isolated canine pulmonary vein rings. Tension and [Ca2+]i were measured simultaneously in fura-2 loaded endothelium-denuded PVSM strips after being permeabilized with alpha-toxin. The effects of the IV anesthetics on tension ([Ca2+]i remains constant) in the absence or the presence of muscarinic receptor activation (acetylcholine) were assessed. The immunofluorescence technique and confocal microscopy were used to localize the cellular distribution of protein kinase C (PKC) isoforms in PVSM cells before and after the addition of ketamine.
Ketamine, etomidate, and midazolam each attenuated acetylcholine contraction dose-dependently, whereas thiopental had no effect. None of the IV anesthetics alone had an effect on tension in strips at constant [Ca2+]i (i.e., they had no direct effect on myofilament Ca2+ sensitivity). Acetylcholine increased tension by 56% +/- 7% at constant [Ca2+]i. In acetylcholine-stimulated strips, etomidate, midazolam, and thiopental had no additional effect on tension at constant [Ca2+]i, whereas ketamine decreased tension by 33% +/- 3%. Activation with acetylcholine induced translocation of PKC from cytoplasm to membrane, and this effect was blocked by ketamine.
Ketamine, etomidate, and midazolam each attenuated acetylcholine-induced pulmonary venous contraction. Ketamine attenuates acetylcholine contraction by inhibiting the acetylcholine-induced increase in myofilament Ca2+ sensitivity and the acetylcholine-induced translocation of PKCalpha.
肺静脉收缩可增加肺毛细血管压力和肺水肿。在本研究中，我们研究了氯胺酮、依托咪酯、硫喷妥钠和咪达唑仑对通透化肺静脉平滑肌（PVSM）中肺静脉收缩和肌丝Ca2+敏感性的直接影响。
在离体犬肺静脉环中评估这些静脉麻醉药对乙酰胆碱收缩的影响。在用α-毒素通透化后，在装载fura-2的去内皮PVSM条带中同时测量张力和[Ca2+]i。评估静脉麻醉药在不存在或存在毒蕈碱受体激活剂（乙酰胆碱）的情况下对张力（[Ca2+]i保持恒定）的影响。在添加氯胺酮之前和之后，使用免疫荧光技术和共聚焦显微镜来定位PVSM细胞中蛋白激酶C（PKC）同工型的细胞分布。
氯胺酮、依托咪酯和咪达唑仑均剂量依赖性地减弱乙酰胆碱收缩，而硫喷妥钠无作用。单独使用这些静脉麻醉药均对[Ca2+]i恒定的条带中的张力无影响（即它们对肌丝Ca2+敏感性无直接影响）。在[Ca2+]i恒定的情况下，乙酰胆碱使张力增加56%±7%。在乙酰胆碱刺激的条带中，依托咪酯、咪达唑仑和硫喷妥钠在[Ca2+]i恒定时对张力无额外影响，而氯胺酮使张力降低33%±3%。乙酰胆碱激活诱导PKC从细胞质易位到细胞膜，而这种作用被氯胺酮阻断。
氯胺酮、依托咪酯和咪达唑仑均减弱乙酰胆碱诱导的肺静脉收缩。氯胺酮通过抑制乙酰胆碱诱导的肌丝Ca2+敏感性增加和乙酰胆碱诱导的PKCalpha易位来减弱乙酰胆碱收缩。
