| ObjectiveThe potential bronchial spasm is usually lethal during the induction of general anaesthesia in patients with airway hyperresponsiveness (AHR) disease, such as COPD, ARDS and so on. The increased risk of bronchial spasm is due to the drug - induced histamine release , decreased sympathetic nerve activity or enhanced parasympathetic activity. For that reason, the choice of the appropriate venous anesthesic is very important for the safety and prognosis of the patients. However , no consensus has been reached in the choice of the proper venous anesthetic that exerts protective effect on airway.Characterized with rapid effect, short duration, immediate elimination, complete recovery, and low incidence of postoperative vomiting, Propofol (PF) , as a new generation of venous anesthetic, has been widely used in clinical anesthesia and ICU sedation Compared with research abroad, the effect of Propofol on airway smooth muscle ( ASM ) tone , especially on that of asthma and on Ryanodine receptor ( RyR) of ASM cell, is poorly reported in our country. Aiming to provide theoretical basis for the choice of the most appropriate anaesthe-sic , our study focused on the pharmacological effects and mechanism of PF on isolated guinea pigs ASM by means of guinea pigs asthma model establishment.Methods1. Establishment of guinea pigs asthma model68 guinea pigs with weight ranging from 150 to 200 g (which provided by Institute of Drug Control, Shenyang) were divided into the normal and asthma group randomly. Sex was not under consideration nor recorded. According to the previous report, our guinea pigs asthma model was established in the way as follows: firstly, the asthma group was sensitized by intraperitoneal injection of 10% ovalbumin ( OA) normal saline; then, after 14 days interval, were given the 1% OA normal saline aerosol inhalation in the 3L glass bell jar once a day for 2 weeks. The success of model establishment was indicated by quickened and deepened constricted obviously breath until obvious contraction of abdominal muscles. For the normal group, 1ml normal saline was given instead of OA normal saline, as well as normal saline aerosol inhalation was adopted instead of OA normal saline administration.2. Preparation of isolated guinea pigs tracheal ringThe guinea pigs were sacrificed by stunning. The tracheas about 2-3 cm were exercised immediately and placed in cold Krebs - Hens-ekeit (KH) solution supplemented with mixed gases (95%O2, 5% CO2). After overlying fatty and connective tissues were dissected , the tracheas were cut into rings of 3 ~ 5 mm width, which were then hung vertically in an organ bath containing 10 ml continuously gassed K-H solution at 37 +0.5C.3. Force measurement of isolated guinea pigs tracheal smooth muscle (TSM)The tension of each tracheal ring was recorded by using a force displacement transducer with a pen recorder attached to the upper end of it. An initial resting load of 2g was applied to each tracheal ring hung in bath that solution was renewed every 20 minutes. The drugswere administrated after 2 hours equilibrium.In our study, the drug concentration here referred to "that of the end stage and cumulative method was adopted in making the dose -effect curve.4. Respective measurement of intracellular and extracellular Ca2 + dependent contraction of guinea pigs TSMAfter equilibrium for 2 hours, the trachea! ring was rinsed by calcium - free K - H solution for 3 times, and then with the interval of 5 minutes to restore the equilibrium, PF at different concentrations was added directly or after preconditioning with 100umol/L Ryanodine for 10 minutes. 20 minutes after PF administration, 0.1umol/L acetyl-choline ( Ach) was added. The contraction of tracheal ring at this moment was the result of intracellular calcium release, so it was also called intracellular calcium dependent contraction. After the maximum contraction appeared, calcium chloride was added into the bath (the end concentration, 2. 5 mmol/L) , and the recontraction of trachea...
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