去氧肾上腺素防治剖宫产腰麻后低血压的效果观察

目的：观察持续输注去氧肾上腺素防治剖宫产腰麻后低血压的效果及安全性。方法：选择ASAⅠ～Ⅱ级,年龄20～32岁的剖宫产术患者60例,全部患者入室后输入复方乳酸钠注射液,输液速度为15～20ml/（kg·h）。将60例患者随机等分两组,A组为对照组,行腰硬联合麻醉,腰麻成功后调整患者体位为15°～20°的左倾斜位至切皮前;B组为观察组,腰麻成功后立即按100μg/ml的速率静脉输注去氧肾上腺素2min,然后按0.3～0.5μg/（kg·min）的速率持续输入至胎儿娩出,余方法同A组。观察两组患者麻醉前及麻醉后2、5、8、10、15、20、25min的SBP,记录低血压的发生率、恶心呕吐发生率及新生儿1min和5min的Apgar评分。结果：A组麻醉后SBP5min及20min下降剧烈,组内与麻醉前比较,P〈0.01,组间比较,P〈0.01;B组麻醉后血压平稳,组内与麻醉前比较,P〉0.05;低血压的发生率及恶心、呕吐发生率A组明显高于B组,P〈0.01;两组新生儿1min和5minApgar评分均在正常范围,组间比较,P〉0.05。结论：持续输注去氧肾上腺素防治剖宫产腰麻后低血压是一种安全有效的方法。     

苯肾上腺素预注射用于剖宫产术脊麻后低血压的剂量效应

目的 探讨苯肾上腺素对剖宫产术脊麻后低血压的合适预注射剂量。 方法 择期行剖宫产术产妇80例,ASAⅠ或Ⅱ级,随机分成4组(n=20):苯肾上腺素预注射50 μg(P1组)、100 μg(P2组)、150 μg(P3组)和对照组(C组,无预注射),快速输注羟乙基淀粉130/0.4氯化钠至胎儿取出前(控制总量≤500 mL,于L_3~4间隙鞘内注入布比卡因9 mg+吗啡0.2 mg,注药后随即产妇平卧位静脉注射上述不同剂量的苯肾上腺素,胎儿取出前若发生产妇低血压,给予适当(50 μg或100 μg)苯肾上腺素静脉注射。 结果 胎儿取出前低血压发生率组间差异无统计学意义(P>0.05),心动过缓发生率组间差异有统计学意义(P<0.05);所有产妇未发生反应性高血压;随着苯肾上腺素预注射剂量增加,各组产妇胎儿取出前平均最低收缩压(SBP)增加,但差异无统计学意义(P>0.05),并且随着鞘内苯肾上腺素预注射剂量的增加低血压出现时间延迟且低血压出现的次数及苯肾上腺素总干预剂量逐渐减小,组间差异均有统计学意义(P<0.05)。术中恶心呕吐发生率,新生儿Apgar评分和脐静脉血气组间差异无统计学意义(P>0.05)。 结论 苯肾上腺素预注射100 μg联合胶体快速输注有利于减少择期剖宫产脊麻后低血压发生次数,心动过缓发生率较低,能较好维持产妇血流动力学稳定。     

Cost of care for patients with age-related macular degeneration in Switzerland and cost-effectiveness of treatment with verteporfin therapy

The cost-effectiveness of photodynamic therapy with verteporfin in the treatment of patients with predominantly classic subfoveal choroidal neovascularization secondary to age-related macular degeneration was investigated by a Markov Model over a time horizon of three years in Switzerland. This model describes patients moving between three levels of visual acuity (e.g., good vision, impaired vision, highly impaired vision) and death in terms of transition probabilities. Transition probabilities as well as effectiveness values were derived from a randomized, controlled, double-masked clinical trial. Effectiveness for verteporfin therapy and for placebo was calculated in terms of vision years: 1.068 and 0.494, respectively. Cost per level of visual acuity was assessed in ascending order by expert panels from a societal perspective. Cost strongly increased parallel with vision loss on a patient-per-year basis from 4683 CHF at good vision to 8443 CHF at impaired vision, and was highest with 15231 CHF at highly impaired vision. The model-calculated cost per visionyear were 14907 CHF for patients in the verteporfin therapy group, versus 21047 CHF for patients in the placebo group. The incremental cost per vision-year additionally saved through verteporfin therapy was 9624 CHF. The study demonstrated that greater effectiveness of verteporfin therapy versus placebo compensated for the cost of the therapy so that verteporfin therapy was clearly costeffective. Therefore, for the indicated patients with AMD that causes severe vision loss, verteporfin therapy can be recommended as the therapy of choice, on both clinical and economic grounds.     

Intracerebroventricular norepinephrine potentiation of the perforant path-evoked potential in dentate gyrus of anesthetized and awake rats: A role for both α- and β-adrenoceptor activation

Norepinephrine (NE) applied iontophoretically to the dentate gyrus in vivo, and bath applied to hippocampal slices in vitro, produces potentiation of the perforant path-evoked potential. β-receptors mediate exogenous NE potentiation in vitro, while α-receptors are implicated in exogenous effects in vivo. The present study uses intracerebroventricular (i.c.v.) NE to mimic in vitro bath conditions in vivo. Short-term NE potentiation was reliably seen with 10 μg [±] NE in 2 μl of 0.9% saline i.c.v. Long-term potentiation occurred with higher doses of NE. The β-agonist isoproterenol and the α-agonist phenylephrine also produced potentiation. Long-term effects were common with isoproterenol. The β-antagonist metoprolol and the α-antagonist phentolamine attenuated NE potentiation. The results suggest that both α- and β-receptors could play a role in NE potentiation in dentate gyrus in vivo. In awake animals, 10 μg NE i.c.v. reproduced the potentiation pattern seen in anesthetized rats. NE potentiation in awake rats was independent of behavioral variation.     

Pharmacokinetic–pharmacodynamic modeling of the effect of propofol on α1-adrenoceptor-mediated positive inotropy in rat heart

Since it is unclear whether and how propofol affects the α₁-mediated inotropic response, we used a pharmacokinetic–pharmacodynamic modeling approach in isolated rat hearts to analyze the effect of propofol on receptor binding and signal transduction. In Langendorff rat hearts perfused with buffer containing 12.3 μM phenylephrine, 1.27 nmol doses of [³H]-prazosin were infused (over 1 min), in the absence and presence of propofol (28 μM). Simultaneous analysis of prazosin outflow concentration and inotropic response (left ventricular developed pressure) using an agonist–antagonist interaction model allowed to estimate receptor affinity, as well as the parameters of the operational model of agonism. Propofol significantly (P < 0.05) increased the negative inotropic effect of prazosin. Modeling suggested that propofol increased the Hill coefficient, which determines the steepness of the stimulus–response curve for the positive inotropic effect of phenylephrine, from 1 to 2.6 ± 0.1 and decreased the maximum achievable inotropic effect from 121.2 ± 12 to 91.8 ± 6 mmHg. Thus, propofol may attenuate the positive inotropic effect of α₁-agonists by decreasing the transduction efficiency of α₁-adrenergic receptor signaling primarily at lower receptor occupancy.     

Intracerebral microdialysis study of glutamate reuptake in awake, behaving rats

The central nervous system has high-affinity uptake systems for the clearance of amino acid transmitters. These systems are found in both neurons and astrocytes. Previous studies have shown that the uptake of amino acid transmitters by astrocytes in culture can be modulated by adrenergic agents. The objectives of this study were to develop a methodology that evaluates the brain's reuptake capacity for glutamate in awake, behaving animals and to determine whether glutamate reuptake is under α-adrenergic regulation in the intact central nervous system. Male Sprague–Dawley rats weighing 250–450 g were used in this study. The extraction fraction of -[³H]glutamate with [¹⁴C]mannitol as a reference was measured. The cortical extraction fraction of -[³H]glutamate corrected for [¹⁴C]mannitol (E _-glu) reaches steady state rapidly and is both stable and repeatable. E _-glu is a measure of -glutamate reuptake and not metabolism. E _-glu is decreased in a dose-dependent manner by the addition of the glutamate reuptake blocker , -threo-β-hydroxyaspartic acid or unlabeled - glutamate. In addition, E _-glu is increased in a dose-dependent manner by the α₁-adrenergic agonist phenylephrine, and this increase is blocked by the α-adrenergic antagonist phentolamine.     

Temporal impairment of microcirculatory perfusion following focal cerebral ischemia in the spontaneously hypertensive rat

Microcirculatory impairments have theoretically been proposed as a potential factor in the development of ischemic injury, but few attempts have been made to directly assess microvascular patency following stroke. To address this issue we investigated the temporal changes in microvascular perfusion induced by permanent focal ischemia. Halothane-anesthetized spontaneously hypertensive rats were subjected to middle cerebral artery occlusion (MCAO) of 5 min to 4 h duration. Two fluorescent tracers (FITC-dextran and Evans blue) were then sequentially administered i.v. and allowed to circulate for 10 and 5 s respectively. Tissue sections were examined by fluorescent microscopy, and the mean number of perfused microvessels/mm² calculated for cortical areas representing non-ischemic (Region A), perifocal/penumbral (Region B) and core ischemic (Region C) regions. For sham-operated controls, virtually all microvessels perfused with tracer within 5 s. In contrast MCAO induced significant reductions in the number of perfused microvessels in Regions B and C. The most marked impairments in perfusion were observed in core MCA territory (e.g. 2–10% of control values for 5 s circulation period) while, initially, the deficit was less severe in penumbral cortex. However, a secondary perfusion impairment developed over time in the perifocal/penumbral region, so that the deficit was greater 4 h after MCAO than at earlier time points (e.g. 72%, 71% and 22% of control value for 0.5, 1 and 4 h MCAO respectively; 10 s circulation period). In conclusion, MCAO induced severe impairments in microcirculatory perfusion within the core ischemic region, and to a lesser extent in the penumbra. However, the development of a more severe perfusion deficit in the penumbra within 4 h of MCAO supports the hypothesis that microcirculatory failure in this region contributes to its recruitment to the ischemic infarct.     

Is α1D-adrenoreptor protein detactable in rat tissues?

We have used the α_1D-adrenoceptor selective antagonist, BMY 7378, the α_1D-selective agonists, adrenaline and phenylephrine, the α_1A-selective antagonists, (+)-niguldipine, SB 216469 and WB4101, and the non-subtype-selective α₁-adrenoceptor antagonist, nemonapride, to investigate the presence of α_1D-adrenoceptors in rat tissues at the protein level. Radioligand binding studies using [³H]prazosin as the radioligand were performed in three tissues containing α_1D-adrenoceptor mRNA, spleen, cerebral cortex and kidney, and in comparison in one tissue not containing α_1D-adrenoceptor mRNA, liver. Cerebral cortex and kidney were also studied upon α_1B-adrenoceptor inactivation by chloroethylclonidine treatment (10 μM, 30 min, 37°C). Experiments with cloned rat α₁-adrenoceptor subtypes transiently expressed in COS cells confirmed the known selectivity of the investigated drugs for α₁-adrenoceptor subtypes or the lack thereof of nemonapride. Accordingly nemonapride had steep and monophasic competition curves in all native and chloroethylclonidine-treated tissues. BMY 7378 also had steep and monophasic competition curves and low affinity in all native tissues. In contrast, adrenaline and phenylephrine (in the presence of 100 μM GTP) had monophasic competition curves of low affinity in liver and spleen but biphasic competition curves in cerebral cortex and kidney. Following chloroethylclonidine treatment competition curves for adrenaline, phenylephrine, (+)-niguldipine, SB 216469 and WB 4101 remained biphasic in cerebral cortex and kidney while those for nemonapride remained monophasic. We conclude that α_1D-adrenoceptors are not readily detectable at the protein level in a variety of rat tissues where their mRNA is expressed. The biphasic competition curves of some agonists and antagonists in chloroethyl-clonidine-treated rat tissues do not represent α_1D-adrenoceptors and are not readily explained by the present α_1A/α_1B/α_1D-adrenoceptor classification. Received: 11 December 1996 / Accepted: 22 January 1997     

pD_2和pA_2的测定

本文采用大鼠肛尾肌分别介绍测定苯肾上腺素ｐＤ＿２和其拮抗剂哌唑嗪ｐＡ＿２的方法。同时讨论了ｐＤ＿２和ｐＡ＿２的意义和推导过程。     

苯肾上腺素对人前列腺上皮细胞增殖和凋亡的作用

目的　探讨交感神经递质对人前列腺上皮细胞增殖和凋亡的作用。方法　在不同浓度的苯肾上腺素下培养人良性前列腺增生 (BPH)上皮细胞系BPH1,观察苯肾上腺素对前列腺上皮细胞增殖和凋亡的影响及其能否被盐酸特拉唑嗪阻断。结果　苯肾上腺素能够刺激体外培养的人前列腺上皮细胞数量增加 ,r1=0 .82 1,P <0 .0 5 ) ;能够增加体外培养的人前列腺上皮细胞上清液A值的增加 ,r2 =0 .85 4,P <0 .0 5 ;能够增加体外培养的人前列腺上皮细胞S期细胞所占的比例(r3 =0 .85 0 ,P <0 .0 5 ) ,这种作用能被盐酸特拉唑嗪阻断。苯肾上腺素不能诱导或抑制体外培养的前列腺上皮细胞发生凋亡。结论　苯肾上腺素能通过α1受体途径刺激前列腺上皮细胞增殖。