Clonidine inhibits the isoproterenol-induced desensitization of the beta noradrenergic activated adenylate cyclase system in astrocytes

Studies were conducted to determine if alpha agonists could influence the desensitization of the beta-noradrenergic receptor activated adenylate cyclase system. Pretreatment of astrocyte cultures with isoproterenol results in a rapid decrease in the cyclic AMP response to subsequent re-exposure to this agonist. The cyclic AMP response to isoproterenol in astrocytes pre-exposed for 2 h to isoproterenol plus clonidine was 2–3 times higher than in cells pre-exposed to isoproterenol alone. The response in astrocytes pretreated with phenylephrine plus isoproterenol was not different from that in cells pretreated with isoproterenol alone. Cyclic AMP may be involved in the effects elicited by clonidine, since this agonist can inhibit the accumulation of cyclic AMP in these cells. Also pretreatment with isobutylmethylxanthine decreases the cyclic AMP response to isoproterenol. The results suggest that clonidine can effect the desensitization of the noradrenergic receptor coupled adenylate cyclase system independent of effects on neurotransmitter release.     

三宝素抗氧化及抗心肌缺血作用的实验研究

本文采用体内和体外实验,研究三宝素的抗氧化及抗心肌缺血的作用。体外法参照肾上腺素红分析法研究三宝素对抗肾上腺素自发氧化的作用,用大鼠作对抗异丙肾上腺素所致的心肌缺血的实验。用小鼠作对抗氰化物中毒性缺氧的影响,结果表明:三宝素明显对抗肾上腺素自发氧化,从而使肾上腺素红生成减少,并能减轻异丙肾上腺素诱发大鼠心肌缺血性损伤作用,但对氰化物中毒性缺氧小鼠无保护作用。提示用本品治疗缺血性心肌病可能有效。     

Bronchoconstriction and delayed rapid shallow breathing induced by cigarette smoke inhalation in anesthetized rats

Bronchomotor and ventilatory responses to inhalation of cigarette smoke (50% concentration, 6 ml) were studied in anesthetized and vagotomized Sprague-Dawley rats. Low-nicotine cigarette smoke did not cause any detectable delayed response, whereas high-nicotine cigarette smoke induced rapid, shallow breathing, and a marked increase in airway resistance (R_L). The increase in f reached a peak (Δf=43±8%) at the 5th breath after the onset of smoke inhalation, preceding both the decrease in V_T (ΔV_T=−27±4%) and the increase in R_L (ΔR_L=89±19%); the latter 2 reached their peaks at approximately the 10th breath, displaying a similar temporal pattern of responses between them. The bronchomotor response to high-nicotine cigarette smoke was slightly attenuated but not prevented by prior administration of isoproterenol (0.2 mg/kg, intravenously [iv]), nor was the smoke-induced rapid, shallow breathing. In contrast, prior administration of mecamylamine (0.9 mg/kg, iv) completely abolished both the bronchomotor and ventilatory responses to smoke inhalation, indicating that nicotine is the primary causative agent responsible for these changes.     

异丙肾上腺素在经皮微球囊压迫三叉神经术中的效果

目的探讨异丙肾上腺素在三叉神经痛经皮微球囊压迫(percutaneous microballoon compression,PMC)中的效果。方法选择2016年5月至2017年12月连续收治的三叉神经痛行PMC的患者45例,男25例,女20例,年龄47~70岁,ASAⅠ或Ⅱ级,采用计算机随机数字表法随机分为两组:研究组(n=23)插管后5min泵注0.9%异丙肾上腺素0.6μg·kg~(-1)·h~(-1)使HR增快至80次/分后开始手术穿刺;对照组(n=22)在HR慢于60次/分时给予阿托品0.5mg静注。记录患者麻醉前(T0)、插管后5min(T_1)、穿刺开始时(T_2)、球囊压迫半月神经节时(T_3)、解除球囊压迫后5min时(T4)的SBP、DBP和HR。计算两组患者SBP、DBP、HR在T_2、T_3时差值的绝对值,分别记为△SBP、△DBP、△HR。记录术中窦性停搏和高血压的发生情况。结果 T0、T_1时两组SBP、DBP、HR差异无统计学意义。T_2、T_3时研究组HR明显快于对照组(P0.05)。研究组△SBP、△DBP明显小于对照组(P0.05)。对照组术中有2例窦性停博。研究组术中高血压发生率明显低于对照组[8(34.8%)vs 14(63.4%),P0.05]。结论 PMC术中使用异丙肾上腺素泵注,与使用阿托品比较,患者BP变化幅度更小,HR增快的幅度更大,为球囊压迫时的HR骤降提供了更加安全的范围。     

A comparison of dopamine,dobutamine and isoproterenol in the treatment of shock

Twelve patients in shock, defined as being present if the mean arterial blood pressure was less than 60 mm Hg, pulmonary arterial occlusion pressure was 15 mm Hg or greater, urine output was 20 ml or less for 2 consecutive hours, and there was clinical evidence of poor peripheral perfusion, underwent a comparative therapeutic trial with dopamine at 200 g · min^-1 and 400 g · min^-1 (2.5–5.5 g · kg^-1 · min^-1), dobutamine 250 g · min^-1 and 500 g · min^-1 (3.5–7 g · kg^-1 · min^-1) and isoproterenol 2 g · min^-1 and 4 g · min^-1 (0.025–0.055 g · kg^-1 · min^-1). Isoproterenol at 2 g · min^-1, produced a significant increase in pulse rate, cardiac output, left ventricular stroke work index and decrease in mean pulmonary blood pressure and pulmonary arterial occlusion pressure and at 4 g · min^-1 a significant increase in stroke volume, mixed venous oxygen tension and decrease in right atrial pressure and systemic vascular resistance was also observed. Dopamine at 200 g · min^-1 produced a significant increase in cardiac output, pulmonary arterial occlusion pressure and mixed venous oxygen tension and at 400 g · min^-1 a significant increase in pulse rate, mean arterial blood pressure mean pulmonary blood pressure, right ventricular stroke work index, right atrial pressure and pulmonary arterial occlusion pressure and decrease in arterial oxygen tension was also observed. Dobutamine at 250 g · min^-1 produced a significant increase in cardiac output, and at 500 g · min^-1 a significant increase in pulse rate, mixed venous oxgen tension and decrease in pulmonary arterial occlusion pressure.All agents increased pulse rate and cardiac output, although in the dosages chosen dopamine was the only agent do so with an increase in pulmonary arterial occlusion pressure and decrease in arterial oxygen tension. In patients in shock if an inotropic agent is considered necessary its pulmonary effect should be considered along with its effect on coronary and peripheral perfusion since dopamine may reduce arterial oxygenation.     

不同年龄组健康人在倾斜试验加异丙肾上腺素中的反应及意义

本文对21例健康人行倾斜试验（HUT）加异丙肾上腺素（ISO），按年龄分为青（25±2．4岁n＝8）、中（40±47岁，n＝8），老（67±2．1岁，n＝5）三组。结果：1例呈阳性反应，占5％；2例不能耐受ISO；2例ISO诱导时心率大于150bpm；16例完成试验呈阴性反应。在基础HUT阶段：80°倾斜与平卧位比较，青中年组的心率和舒张压（DBP）均有显著升高，老年组无显著差异。在HUT＋ISO阶段：80℃倾斜与平卧比较，三组心率均显著升高，至ISO3ug/min时，青年组DBP下降。在上述两阶段中，收缩压无显著性变化。结论：①HUT±ISO在正常人中的阳性率在5％左右。②对HUT＋ISO存在年龄差异，老年人反应性较差。     

异丙肾上腺素预处理对大鼠胰腺移植后缺血再灌注损伤的抑制作用

目的:探讨减轻大鼠胰腺移植后缺血再灌注损伤的保护作用机制.方法:IPC后动态检测大鼠胰腺组织热休克蛋白表达.建立大鼠胰腺移植缺血再灌注模型,选择表达热休克蛋白高峰时段供体大鼠胰腺移植作为实验组,未预处理供体大鼠胰腺移植作为对照组.移植后6 h,采集静脉血及移植胰腺.热休克蛋白70(HSP70)分别用Western blot法及免疫组织化学法检测.免疫组织化学法测定肿瘤坏死因子-α(TNF-α)表达.流式细胞仪检测胰腺细胞凋亡率.碘淀粉比色法检测血淀粉酶水平.结果:IPC后供体大鼠胰腺中HSP70的表达在24 h达到高峰,与其他各时段比较具有显著差异(0.92±0.25 vs 0.24±0.04,0.34±0.06,0.58±0.07,0.62±0.11,0.25±0.09,均P<0.05),IPC后6 h,12 h,24 h,36 h大鼠胰腺中HSP70的表达与未预处理组相应时段比较差异也显著(0.34±0.06 vs 0.28±0.07,0.58±0.07 vs 0.25±0.04.0.92±0.25 vs 0.27±0.05,0.62±0.11vs 0.25±0.06,均P<0.05),48 h恢复到原来水平.而未预处理组各时段间比较差异无统计学意义(P>0.05).HSP70主要表达于胰腺腺泡细胞及血管壁.对照组胰腺组织中TNF-α、细胞凋亡率、中性粒细胞、血淀粉酶的水平明显升高,与假手术组相比差异显著(均P<0.01).实验组降低了胰腺组织中TNF-α、细胞凋亡率、白细胞数、血淀粉酶的水平,与对照组比较差异具有统计学意义(11 929±1220vs46 111±3127,26.7%±4.5%vs 37.4%±4.7%,3 308±531 vs 6668±1506,1057 IU/L±148IU/L vs 1 408 IU/L±195IU/L,均P<0.05).结论:IPC减轻了大鼠胰腺移植后缺血再灌注损伤,IPC保护作用与HSP70的诱导生成有关.     

3/4肾切除并异丙肾皮下注射致慢性心衰合并肾衰模型的制备

目的:研究大鼠3/4肾切除并异丙肾上腺素(ISO)皮下注射致慢性心衰合并肾衰模型的制备.方法:雄性SD大鼠经“两次手术切除法”行3/4肾切除,1周后分成2组,分别皮下注射ISO(70 mg/kg或100 mg/kg,分2次,间隔24 h),对照组给予假手术并注射生理盐水,4周后比较各组大鼠存活率、心衰及肾衰情况.试剂盒法测定血清肌酐、尿素氮,Bradford法测定24 h尿蛋白量,左心室插管术测定左室收缩压(LVSP)、左室舒张压(LVDP)、左室舒张末压(LVEDP)及左室压力最大上升及下降速率(±dp/dtmax).称重法测定心脏重量参数.切片HE染色观测心肌病理情况.结果:对照组大鼠无死亡,大小剂量模型存活率分别为73％、87％,与对照组相比,大小剂量模型组大鼠血清各项指标、尿蛋白明显升高,LVSP下降,LVDP和LVEDP均上升,心脏重量参数比升高,提示左室舒张和收缩功能损伤,发生左室心衰和左室心肌肥厚重构.且大剂量组与小剂量组比较心肾功能差异有统计学意义.结论:3/4肾切除并ISO(100 mg/kg)皮下注射较ISO(70 mg/kg)皮下注射,更易同时诱发大鼠左室心衰及肾衰.     

Differential effects of estradiol on drinking by ovariectomized rats in response to hypertonic NaCl or isoproterenol: Implications for hyper- vs. hypo-osmotic stimuli for water intake

We examined the effects of estradiol on behavioral responses to osmotic challenges in ovariectomized (OVX) rats to test the hypothesis that estradiol enhances sensitivity to gradual changes in plasma osmolality (pOsm) in stimulating water intake. Despite comparably elevated pOsm after a slow infusion of 2 M NaCl, the latency to begin water intake was significantly less in estradiol-treated OVX rats compared to that in oil vehicle-treated rats. Other groups of OVX rats were injected with isoproterenol, which increases circulating angiotensin II. These rats then were given 0.15 M NaCl to drink instead of water, to prevent decreased pOsm associated with water ingestion. Isoproterenol stimulated 0.15 M NaCl intake by both groups; however, estradiol-treated rats consumed less 0.15 M NaCl than did oil-treated rats, findings that are similar to those reported when estradiol-treated rats consumed water. The estradiol enhancement of sensitivity to increased, but not to decreased, pOsm suggests that estradiol has directionally-specific effects on osmoregulatory drinking. Moreover, the estradiol attenuation of 0.15 M NaCl intake after isoproterenol suggests that estradiol effects on osmoregulatory drinking are independent of those on volume regulatory drinking.     

Intercalated duct cells in the rat parotid gland may behave as tissue stem cells

This study was conducted to determine whether intercalated duct cells in the rat parotid gland have the properties of tissue stem cells. After induction of cellular proliferation by repeated administration of isoproterenol (IPR), a β-adrenergic agonist, proliferation activity in acinar, intralobular, and intercalated ductal cells was quantified using Ki-67 immunohistochemistry. The total number of each type of component cell in a gland was also estimated in the course of IPR treatment. IPR was found to induce proliferation of acinar and intercalated duct cells, but not intralobular duct cells. The total number of acinar cells in a gland on day 5 of IPR treatment was 1.6 times of that at day 0 (baseline). In contrast, the total numbers of intercalated and intralobular duct cells did not change from baseline, indicating a high possibility that the proliferated intercalated duct cells differentiated into acinar cells. On days 2 to 3 of IPR treatment, intercalated duct cells with amylase-positive secretory granules were recognized in a region very close to the acini, and were suspected of being transitional cells from intercalated duct to acinar cells. This quantitative study indicates that intercalated duct cells may have the properties of tissue stem cells upon IPR stimulation.