普罗帕酮对麻醉兔左心室后负荷变化引起的电生理改变的影响

目的：探讨普罗帕酮（Ｐｒｏ）对兔左心室后负荷变化引起的心室电生理改变的作用．方法：Ｐｒｏ３ｍｇ·ｋｇ－１ｉｖ前后，改变左心室后负荷，观察室性心律失常发生情况；并测定左心室舒张阈值（ＶＤＴ），相对不应期（ＲＲＰ），有效不应期（ＥＲＰ）及其不应期离散和心室纤颤阈（ＶＦＴ）．结果：增加左心室后负荷（Ｂ级），可使左室ＲＲＰ和ＥＲＰ时间离散增加，ＶＦＴ降低，并出现室性心律失常．Ｐｒｏｉｖ后，ＶＤＴ，ＲＲＰ，ＥＲＰ，ＶＦＴ均较用药前显著延长或升高（Ｐ＜００１）；改变左室后负荷，心室电生理参数无显著改变（Ｐ＞００５）．结论：Ｐｒｏ可抑制左室后负荷增加引起的不应期离散增大和ＶＦＴ降低，起到抗室性心律失常的作用．     

Nitric oxide induces neurotransmitter release from hippocampal slices

Hydroxylamine (1–300 μM), a nitric oxide generator, stimulated the release of [³H]norepinephrine ([³H]NE) and [¹⁴C]acetylchoIine ([¹⁴C]ACh) from rat hippocampal slices in a concentration-dependent manner (EC₅₀ = 30 μM). A maximally effective concentration of hydroxylamine (300 μM) produced a 24-fold increase in the basal [³H]NE and 3.6-fold increase in the in the basal [¹⁴C]ACh efflux. Sodium nitroprusside (SNP), also stimulated the release of [³H]NE, but only at high concentrations (10–30 mM). Calcium-free experimental buffer (1 mM EGTA) abolished the response. Hemoglobin (0.3 μM) inhibited the effect of 100 μM hydroxylamine in a manner which was specific for nitric oxide. In addition, 100 μM hydroxyiarnine increased the efflux of endogenous GABA and glutamate by 3- and 6-fold, respectively.     

Does sodium nitroprusside reduce lung injury under cardiopulmonary bypass?

Objective: We hypothesized that direct pulmonary arterial infusion of sodium nitroprusside (SNP) would ameliorate lung injury under cardiopulmonary bypass. Methods: Experiments were performed on 12 adult mongrel dogs of both sexes weighing 20–28 kg. The animals were randomly divided into two groups of six animals each. All animals were subjected to total cardiopulmonary bypass (CPB) and moderate hypothermia (28°C core temperature). During total CPB, the aorta was clamped together with the pulmonary artery to prevent any antegrade flow to the lungs. After cardioplegic arrest for 120 min, the animals were rewarmed, weaned from CPB, and their condition stabilized for another 90 min. After the release of the aortic cross-clamp, the dogs received either a 5% glucose solution as a placebo (group I) or SNP (0.5 μg/kg per min) (group II), both infused into the pulmonary arterial line. The infusion was stopped after 60 min. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes count, lung tissue samples were taken before CPB and after weaning from CPB. In addition, alveolar-arterial oxygen difference (AaDO₂) for tissue oxygenation was calculated by obtaining arterial blood gas samples. Results: Values of MDA before CPB of 42.0±5.3 nmol/g of tissue rose to 67.6±5.7 nmol/g of tissue after weaning from CPB in group I (P=0.028). In group II MDA values also increased from 43.1±4.3 to 52.4±5.7 nmol MDA/g of tissue after weaning from CPB (P=0.046). The MDA increase in group II after CPB was found to be significantly lower than that for group I (P=0.004). The wet-to-dry lung weight ratio in the sodium nitroprusside group was 5.1±0.2, significantly lower than in the control group (6.8±0.4), (P=0.01). AaDO₂ increased significantly in group I (P=0.028). There was no statistically significant difference (P=0.065) between groups I and II. During histopathological examination it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups. The increase in group I was significantly larger than that in group II (P<0.001). Conclusions: The results represented in our study indicate that pulmonary arterial infusion of sodium nitroprusside during reperfusion can reduce lung injury under cardiopulmonary bypass.     

Heterogeneity in epithelium-dependent responses

The airway epithelium exerts a profound influence on the responsiveness of bronchial smooth muscle to both contracting and relaxing agents. This may be due to the release of an epithelium-derived factor or factors. There is a considerable heterogeneity in the effects of the epithelium between orders of bronchi, between species, and between pharmacologic agents. Such heterogeneity may reflect variations in the release and/or effect of the epithelium-derived relaxing factor(s). This report demonstrates that: (1) there is a basal and a stimulated release of the factor, (2) the prominence of different types of release varies between species, (3) the effect of the epithelium on relaxation of bronchial smooth muscle is greatest in the presence of high degrees of cholinergic tone, (4) the effects of the epithelium are not mediated via cyclic GMP, and (5) the epithelium-derived relaxing factor is not nitric oxide.     

一氧化氮供体诱导HL-60细胞凋亡过程中活性氧自由基和抗氧化能力的变化

为了研究外源性一氧化氮（NO）供体硝普钠（SNP）诱导HL-60细胞凋亡过程中活性氧自由基和抗氧化能力的变化，将HL-60细胞与SNP在体外培养，用MTT法观察NO对细胞的抑制作用；用透射电子显微镜和光学显微镜观察细胞结构的变化；用DNA凝胶电泳、细胞DNA含量、Annexin-V／PI法等分析细胞凋亡；用双氢罗丹明123（DHR）标记、流式细胞仪检测细胞内活性氧（ROS），并同时测定细胞内谷胱甘肽（GSH）和3种抗氧化酶的活性。结果表明：SNP能抑制HL-60细胞生长，典型的细胞形态改变、DNA片段化、亚二倍体峰比例增加、DNA末端标记和Annexin-V^＋／PI^-表达增加等证实NO能诱导白血病细胞凋亡，且两者之间有明显的量效和时效关系。在此过程中，细胞内ROS水平增加，细胞内谷胱甘肽和过氧化氢酶（CAT）、谷胱甘肽S转移酶（GST）、谷胱甘肽过氧化物酶（GPX）活性降低。ROS含量和CAT、GST、GPX活性与SNP之间也有明显的量效关系。结论：细胞内活性氧自由基增加和抗氧化能力下降在外源性一氧化氮供体诱导HL-60细胞凋亡中发挥了重要作用。     

Nitric Oxide and Superoxide Anion in Low-Grade Esophagitis Induced by Acid and Pepsin in Rabbits

It has been suggested that free radicals are involved in esophagitis. To study the role and potential interaction of superoxide anion and nitric oxide (NO) in low-grade esophagitis, we perfused acidified pepsin (30 min every 12 hr) for seven days in rabbits treated with different agents to modulate the generation of these radicals. Measurements included macroscopic and microscopic damage, superoxide anion generation, mucosal nitric oxide synthase activity, and peroxynitrite formation. Low-grade esophagitis was associated with increased nitric oxide synthase mucosal activity and mucosal damage was dose-dependently increased by treatment with the NO synthase inhibitor N ^G-nitro-l-arginine. Superoxide anion was scarcely generated in the mucosa, but this was not accompanied by any change in the activity of mucosal superoxide dismutase. Treatment with superoxide dismutase did not improve mucosal damage. Generation of peroxynitrites was not detected. In conclusion, nitric oxide is involved in the mucosal defense of the esophagus against acid- and pepsin-induced damage. Superoxide anion generation seems irrelevant in the induction of low-grade esophagitis and not sufficient to interact with nitric oxide to generate measurable mucosal peroxynitrite radicals.     

Pharmacological MRI of the choroid and retina: Blood flow and BOLD responses during nitroprusside infusion

Nitroprusside, a vasodilatory nitric oxide donor, is clinically used during vascular surgery and to lower blood pressure in acute hypertension. This article reports a novel application of blood flow (BF) and blood oxygenation level dependent (BOLD) MRI on an 11.7T scanner to image the rat chorioretinal BF and BOLD changes associated with graded nitroprusside infusion. At low doses (1 or 2 μg/kg/min), nitroprusside increased BF as expected but decreased BOLD signals, showing an intriguing BF–BOLD uncoupling. At high doses (3?5 μg/kg/min), nitroprusside decreased BF and markedly decreased BOLD signals. To our knowledge, this is the first pharmacological MRI application of the retina. This approach has potential to open up new avenues to study the drug‐related hemodynamic functions and to evaluate the effects of novel therapeutic interventions on BOLD and BF in the normal and diseased retinas. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Impaired Sympathetic Baroreflexes in Prehypertensive Dahl Hypertension-Sensitive Rats

Baroreflex responsiveness was assessed in Dahl rats that had been fed a low-salt diet to retard subsequent development of hypertension. After five weeks there were no differences in baseline pressures, but all responses elicited reflexly by elevating blood pressure with phenylephrine were less pronounced in hypertension-sensitive (DS) than in hypertension-resistant (DR) rats. Diminished responses included the following: acceleration in afferent aortic nerve activity, bradycardia, and inhibition of splanchnic and renal sympathetic nerve activity. By contrast, opposite responses elicited by lowering blood pressure with sodium nitroprusside did not differ significantly. Selective baroreflex attenuation (i.e. which was demonstrable only when blood pressure was elevated but not when it was lowered) in DS rats may have been due to differences either in pharmacology of the two drugs, or in sinoaortic vessel wall geommetry. The baroreflex impairment shown here could represent a genetic predisposition that eventually elevates blood pressure in DS rats by increasing sympathetic vasomotor tone in the renal and splanchnic vascular beds.     

Clevidipine in the treatment of perioperative hypertension: assessing safety events in the ECLIPSE trials

Interview with Professor Chris Packard, MD, PhD by Tanya Stezhka (Commissioning Editor)

The IMPROVE-IT trial, launched 9 years ago, has finally provided physicians with long-term efficacy and safety evidence for ezetimibe. The large-scale study in acute-coronary-syndrome patients showed a clear benefit in reducing cardiovascular events when added to simvastatin in this population. The size of the benefit was proportionate to the reduction in LDL cholesterol.

We spoke to Professor Chris Packard (University of Glasgow, UK) about his interest in the trial, and the importance of lowering LDL and research in the wider clinical context.     

硝普钠控制性降压用于脊柱手术的临床研究

目的:探讨硝普钠控制性降压在脊柱手术中的临床应用。方法:72例拟在全麻下行脊柱手术患者随机分成两组:观察组(硝普钠组,n=36)与对照组(n=36)。所有患者均静脉注射咪唑安定0.1mg.kg-1、丙泊酚2mg.kg-1、芬太尼2μg.kg-1和采用预注给药的阿曲库铵进行气管内插管,以异氟醚或氨氟醚、阿曲库铵和芬太尼维持麻醉。观察组在手术进入椎体前3～5min由输液泵输入0.01%硝普钠,控制速度使收缩压维持于60～80mmHg的范围。记录两组出血量、输血量、输液量、手术时间,术后1h血红蛋白与术前血红蛋白等。结果:两组患者基本情况、手术类型、晶体液、胶体液输入量无统计学差异;观察组术中失血量和输血量均明显少于对照组,且手术时间明显缩短;两组术后1h血红蛋白与术前比较均有所下降,但差异无显著性。结论:脊柱手术中采用硝普钠控制性降压效果安全、可靠,可明显减少术中出血量及输血量,缩短手术时间。