BACKGROUND & AIMS: :To compare the early postarrest inflammatory cytokine response between animals administered amiodarone (AMIO) and lidocaine (LIDO) intra-arrest during resuscitation from ventricular fibrillation (VF). Domestic swine (n=32) were placed under general anesthesia and instrumented before spontaneous VF was induced by balloon occlusion of the left anterior descending coronary artery. After 7 min of VF, standard ACLS resuscitation was performed and animals were randomized to either bolus AMIO (5 mg/kg, n=13) or LIDO (1 mg/kg, n=14) for recurrent or refractory VF. A non-antiarrhythmic (n=5) was also used for comparison. Following return of spontaneous circulation (ROSC), tumor necrosis factor (TNF)-α levels were drawn at 30 and 60 min. Groups were comparable with respect to prearrest hemodynamics and resuscitation variables. In the postarrest period, the LIDO and non-antiarrhythmic group demonstrated virtually identical TNF-α response trajectories. However, TNF-α levels were significantly higher in AMIO- than LIDO-treated animals at 30 min (geometric mean 539 versus 240 pg/mL, 2.2-fold higher, 95% confidence interval [CI] 1.3-3.8-fold higher, P=0.003) and at 60 min (geometric mean 570 versus 204 pg/mL, 2.8-fold higher, 95% CI 1.1-7.0-fold higher, P=0.03). Significant differences in the postarrest TNF-α levels were observed between animals treated with AMIO as compared to those treated with LIDO. Improved rates of ROSC seen with AMIO may come at the expense of a heightened proinflammatory state in the postcardiac arrest period.

背景与目标： : 比较在室颤 (VF) 复苏期间给予胺碘酮 (AMIO) 和利多卡因 (LIDO) 的动物之间的早期后炎症细胞因子反应。将家养猪 (n = 32) 置于全身麻醉下，并在左前降支冠状动脉球囊闭塞诱发自发性VF之前进行器械治疗。VF 7  min后，进行标准ACLS复苏，并将动物随机分配给反复发作或难治性VF的AMIO (5  mg/kg，n = 13) 或LIDO (1  mg/kg，n = 14)。还使用非抗心律失常药 (n = 5) 进行比较。自发循环 (ROSC) 后，在30和60  min时测定肿瘤坏死因子 (TNF)-α 水平。两组在预停血流动力学和复苏变量方面具有可比性。在最后期，LIDO和非抗心律失常组表现出几乎相同的TNF-α 反应轨迹。然而，在30  min时，AMIO-的TNF-α 水平明显高于LIDO处理的动物 (几何平均539与240  pg/mL相比，高2.2倍，95% 置信区间 [CI] 高1.3-3.8倍，P = 0.003) 和60分钟时 (几何平均570与204  pg/mL相比，高2.8倍，95% CI高1.1-7.0倍，P = 0.03)。与用LIDO治疗的动物相比，用AMIO治疗的动物之间的starrest TNF-α 水平存在显着差异。用AMIO观察到的ROSC率提高可能是以心脏骤停后炎症状态增强为代价的。

BACKGROUND & AIMS: BACKGROUND:Lidocaine and amiodarone are both included in the pediatric cardiac arrest guidelines as treatments of shock-refractory ventricular fibrillation or pulseless ventricular tachycardia, although there is limited evidence to support this recommendation. METHODS:In this cohort study from the Get With The Guidelines - Resuscitation registry, we included pediatric patients (≤18 years) with an in-hospital cardiac arrest between 2000 and 2018, who presented with an initial or subsequent shockable rhythm (ventricular fibrillation and pulseless ventricular tachycardia). Patients receiving amiodarone were matched to patients receiving lidocaine based on a propensity score, calculated from multiple patient, event, and hospital characteristics. RESULTS:A total of 365 patients were available for the analysis, of which 180 (49%) patients were matched on the propensity score. The median age in the raw cohort was 6 (quartiles, 0.5-14) years, 164 (45%) patients were female, and 238 (65%) patients received an antiarrhythmic for an initial shockable rhythm. In the matched cohort, there were no statistically significant differences between patients receiving lidocaine compared to amiodarone in return of spontaneous circulation (RR, 0.99 [95%CI, 0.82-1.19]; p = 0.88), survival to 24 h (RR, 1.02 [95%CI, 0.76-1.38]; p = 0.88), survival to hospital discharge (RR, 1.01 [95%CI, 0.63-1.63]; p = 0.96), and favorable neurological outcome (RR, 0.65 [95%CI, 0.35-1.21]; p = 0.17). The results remained consistent in multiple sensitivity analyses. CONCLUSIONS:In children with cardiac arrest receiving antiarrhythmics for a shockable rhythm, there was no significant difference in clinical outcomes between those receiving lidocaine compared to amiodarone.

背景与目标：

BACKGROUND & AIMS: :The antiadrenergic actions of amiodarone (Am) are well known but its effect and that of its metabolite, desethylamiodarone (DAm), on beta-receptor density (Bmax) and affinity (KD) are poorly defined. Thus, the acute and chronic effects of Am and DAm on myocardial beta-receptors in rabbits were determined relative to changes in thyroid hormones and serum and tissue drug concentrations. Bmax and KD were measured by radio-ligand binding, thyroid hormones by RIA, and drug levels by HPLC. Compared with controls, intravenous Am (20 mg/kg) reduced Bmax by 23% (p less than 0.05) and DAm (20 mg/kg) by 32% (p less than 0.05). After 3 weeks of chronic drug, the corresponding value for Am was 24% (p less than 0.05) versus 45% (p less than 0.05) for DAm. The effect of DAm was significantly greater (p less than 0.05) than that of Am, being comparable to that of Am (-44%) after 6 weeks. In the case of Am, doubling the dose (and myocardial level) led to no further decrease in Bmax. DAm also reduced Bmax more following chronic treatment than after acute administration (-45 versus -32%), a difference of borderline significance. Following 3 weeks of p.o. Am, T3 decreased 3% (NS) and reverse T3 (rT3) increased 90% (p less than 0.05); after 6 weeks, the corresponding values were 25% (p less than 0.05) and 181% (p less than 0.01). After 1 week of p.o. DAm, T3 did not change but rT3 increased by 34% (p less than 0.05); after 3 weeks the corresponding values were 21% (p less than 0.01) and 64% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 胺碘酮 (Am) 的抗肾上腺素作用是众所周知的，但其作用及其代谢物去乙基胺碘酮 (DAm) 对 β 受体密度 (Bmax) 和亲和力 (KD) 的作用尚不明确。因此，相对于甲状腺激素以及血清和组织药物浓度的变化，确定了Am和DAm对兔心肌 β 受体的急性和慢性影响。通过放射配体结合测量Bmax和KD，通过RIA测量甲状腺激素，通过HPLC测量药物水平。与对照组相比，静脉内Am (20 mg/kg) 将Bmax降低23% (p小于0.05)，将DAm (20 mg/kg) 降低32% (p小于0.05)。慢性用药3周后，Am的相应值为24% (p小于0.05)，而DAm的相应值为45% (p小于0.05)。大坝的效果明显大于Am (p小于0.05)，6周后与Am (-44%) 相当。在Am的情况下，剂量 (和心肌水平) 加倍导致Bmax没有进一步降低。与急性给药 (-45对-32%) 相比，长期治疗后DAm还降低了Bmax，这具有临界意义。经过3周的p.o.Am、T3下降3% (NS) 和反向T3 (rT3) 上升90% (p小于0.05); 6周后，相应值分别为25% (p小于0.05) 和181% (p小于0.01)。一周后的p.o.DAm，T3没有变化，但rT3增加了34% (p小于0.05); 3周后相应的值分别为21% (p小于0.01) 和64% (p小于0.01)。(摘要截断在250个单词处)

BACKGROUND & AIMS: :A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the administration of amiodarone or lidocaine in patients with refractory VT/VF after cardiac surgery results in successful cardioversion. Altogether more than 434 papers were found using the reported search, from which 23 articles were used to answer the clinical question. No randomized trials have been found in which amiodarone was studied in patients with refractory VF/VT after cardiac surgery. Recommendations on the use of amiodarone in patients with refractory VF/VT in both European and American 2005 Guidelines on Resuscitation are mainly based on expert consensus and are supported by a few randomized trials in patients with out-of-hospital cardiac arrest. We would therefore recommend that amiodarone is the first line drug that should be used in patients with refractory ventricular arrhythmias after cardiac surgery that persist after three failed attempts at cardioversion. Lidocaine should only be used if amiodarone is not available or if its use is contraindicated. Amiodarone should be administered as an intravenous bolus of 300 mg after the third unsuccessful shock.

背景与目标： : 根据结构化协议编写了心脏外科手术的最佳证据主题。解决的问题是，在心脏手术后难治性VT/VF患者中使用胺碘酮或利多卡因是否可以成功进行复律。使用报告的搜索总共发现了434多篇论文，其中23篇文章用于回答临床问题。尚未发现在心脏手术后难治性VF/VT患者中研究胺碘酮的随机试验。欧洲和美国2005复苏指南中关于难治性VF/VT患者使用胺碘酮的建议主要基于专家共识，并得到了一些针对院外心脏骤停患者的随机试验的支持。因此，我们建议胺碘酮是一线药物，应用于心脏手术后难治性室性心律失常的患者，在三次心脏复律失败后持续存在。利多卡因仅应在胺碘酮不可用或禁忌使用的情况下使用。在第三次不成功的休克后，胺碘酮应静脉推注300 mg。

BACKGROUND & AIMS: :Probe-based confocal laser endomicroscopy (pCLE) allows microscopic imaging of the alveoli during bronchoscopy. The objective of the study was to assess the diagnostic accuracy of pCLE for amiodarone-related pneumonia (AMR-IP). Alveolar pCLE was performed in 36 nonsmoking patients, including 33 consecutive patients with acute or subacute interstitial lung disease (ILD), of which 17 were undergoing treatment with amiodarone, and three were amiodarone-treated patients without ILD. Nine out of 17 patients were diagnosed with high-probability AMR-IP (HP-AMR-IP) by four experts, and three separate observers. Bronchoalveolar lavage findings did not differ between HP-AMR-IP and low-probability AMR-IP (LP-AMR-IP) patients. In HP-AMR-IP patients, pCLE showed large (>20 μm) and strongly fluorescent cells in 32 out of 38 alveolar areas. In contrast, these cells were observed in only two out of 39 areas from LP-AMR-IP patients, in one out of 59 areas from ILD patients not receiving amiodarone and in none of the 10 areas from amiodarone-treated patients without ILD (p<0.001; HP-AMR-IP versus other groups). The presence of at least one alveolar area with large and fluorescent cells had a sensitivity, specificity, negative predictive value and positive predictive value for the diagnosis of AMR-IP of 100%, 88%, 100% and 90%, respectively. In conclusion, pCLE appears to be a valuable tool for the in vivo diagnosis of AMR-IP in subacute ILD patients.

背景与目标： : 基于探针的共聚焦激光显微镜 (pCLE) 允许在支气管镜检查期间对肺泡进行显微成像。该研究的目的是评估pCLE对胺碘酮相关性肺炎 (amr-ip) 的诊断准确性。对36例非吸烟患者进行了肺泡pCLE，其中包括33例连续的急性或亚急性间质性肺病 (ILD) 患者，其中17例接受胺碘酮治疗，3例接受胺碘酮治疗，无ILD。17名患者中有9名被4名专家和3名独立的观察员诊断为高概率amr-ip (hp-amr-ip)。Hp-amr-ip和低概率amr-ip (lp-amr-ip) 患者的支气管肺泡灌洗发现没有差异。在hp-amr-ip患者中，pCLE在38个肺泡区域中的32个显示大 (> 20μm) 和强荧光细胞。相比之下，这些细胞仅在来自lp-amr-ip患者的39个区域中的两个区域中观察到，在来自未接受胺碘酮的ILD患者的59个区域中的一个区域中，在未接受胺碘酮治疗的ILD患者的10个区域中没有一个区域中观察到 (p<0.001; hp-amr-ip与其他组)。至少一个具有大细胞和荧光细胞的肺泡区域的存在对100% 、88% 、100% 和90% 的amr-ip的诊断分别具有敏感性、特异性、阴性预测值和阳性预测值。总之，pCLE似乎是亚急性ILD患者体内诊断amr-ip的有价值的工具。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: BACKGROUND:Intravenous (IV) amiodarone has multiple indications including treatment of hemodynamically unstable patients and the prevention of atrial or ventricular arrhythmias after thoracic surgery. Inflammation of the vein, or phlebitis, is the most common adverse event associated with peripherally administered amiodarone. In 2017, a rise in reported phlebitis incidents was occurring at one large academic medical center. AIM:This evidence-based quality improvement initiative aimed to decrease and enhance early detection of phlebitis in patients receiving amiodarone. METHODS:Due to the variation in assessment and management standards, evidence-based practice (EBP) methodology was utilized to establish a process for quality improvement. A thorough literature search was completed, identifying evidence-based interventions to decrease phlebitis and enhance early detection. Thorough critiques of the literature and synthesis of the evidence were completed. Multidisciplinary guidelines based on the literature were created. The guidelines included interventions such as an increase in IV assessment frequency, vein selection criteria, and the utilization of a standardized grading tool for assessment. RESULTS:Phlebitis was reduced by 30%-88%. In the first 6 months post-intervention, there was a 48% reduction in phlebitis cases. In addition, the severity of phlebitis and the quality of reporting also improved dramatically. LINKING EVIDENCE TO ACTION:This evidence-based quality improvement process led to identifying relevant knowledge gaps in care that could be streamlined into everyday nursing practice to decrease patient harm. This paper describes an in-depth process of how EBP helped to quickly take a clinical inquiry and adapt change based on findings from the evidence. Other organizations can utilize EBP to solve patient safety concerns using similar processes.

背景与目标：

BACKGROUND & AIMS: It has been shown that thyroid hormone has a significant effect on the heart and that suppression of thyroid function may contribute to the antiarrhythmic effect of amiodarone. The study was aimed at investigating the effects of hypothyroidism, compared with those of amiodarone, on vulnerability to ventricular fibrillation in dogs. In this study, 25 adult dogs were randomly divided into three groupsa hypothyroid group following total thyroidectomy (n = 9), an amiodarone group (n = 8, 400 mg per day, 4 weeks), and a control group (n = 8). Both amiodarone and control groups were subjected to sham surgery. Five to 8 weeks after surgery, ventricular fibrillation threshold and other electrophysiological parameters were determined. Right ventricular effective refractory period, monophasic action potential duration, and ventricular fibrillation threshold were significantly increased in both the thyroidectomized and amiodarone-treated animals. There was no significant change in monophasic action potential duration dispersion. The incidence of ventricular fibrillation during ischemia and reperfusion was significantly reduced in both treated groups compared with the sham-operated euthyroid controls. These observations suggest that hypothyroidism has a significant antifibrillatory effect in dogs. Homogeneous prolongation of repolarization and refractoriness may contribute to the antifibrillatory action of hypothyroidism.

背景与目标： 研究表明，甲状腺激素对心脏有重要作用，甲状腺功能的抑制可能有助于胺碘酮的抗心律失常作用。该研究旨在研究甲状腺功能减退症与胺碘酮相比对犬心室颤动的影响。在这项研究中，将25只成年犬随机分为三组，即全甲状腺切除术后甲状腺功能减退组 (n = 9)，胺碘酮组 (n = 8，每天400 mg，4周) 和对照组 (n = 8)。胺碘酮和对照组均接受假手术。术后5 ~ 8周，测定心室颤动阈值及其他电生理参数。在甲状腺切除和胺碘酮治疗的动物中，右心室有效不应期，单相动作电位持续时间和心室颤阈值均显着增加。单相动作电位持续时间离散度无明显变化。与假手术的甲状腺功能正常对照组相比，两个治疗组在缺血和再灌注期间心室纤颤的发生率均显着降低。这些观察结果表明，甲状腺功能减退症对狗具有明显的抗纤颤作用。复极化和难治性的均匀延长可能有助于甲状腺功能减退的抗纤作用。

BACKGROUND & AIMS: :The rapidly developing resistance of fungi to antifungal drugs is a serious health problem. Today's drugs mainly target cell membrane composition and synthesis. Moreover, some of them have serious side effects. New antifungal drugs targeting different molecular pathways are necessary. Amiodarone, an FDA approved antiarrhythmic drug displays antifungal activity. It targets calcium and pH homeostasis. In concentrations above 25 μM, it inhibits the growth of the filamentous fungi Aspergillus niger. It triggers a biphasic calcium response accompanied by a high [Ca(2+)](c) resting level and an intracellular acidification from 7.5 to 6.0, both of which are concentration dependent. Both extracellular calcium and calcium from intracellular organelles are sources of the transient second cytosolic calcium peak, whose amplitude is 0.12 μM for cells treated with 0.1mM amiodarone. In P-type ATPase deficient A. niger strains pmrAΔ and pmcAΔ, the [Ca(2+)](c) resting level after amiodarone treatment is at least twice as high as that of the wild type, which correlates with fungal viability and hypersensitivity to amiodarone. A combination of amiodarone and amphotericin B is additive in terms of cell viability and cytosolic calcium influx. In contrast, a combination of azole drugs and amiodarone has a synergistic effect on the viability of fungi.

背景与目标： : 真菌对抗真菌药物的耐药性迅速发展，是一个严重的健康问题。当今的药物主要是靶向细胞膜的组成和合成。此外，其中一些有严重的副作用。针对不同分子途径的新型抗真菌药物是必要的。胺碘酮是FDA批准的抗心律失常药物，具有抗真菌活性。它的目标是钙和pH稳态。在25μm以上的浓度下，它会抑制丝状真菌黑曲霉的生长。它触发双相钙反应，伴随着高 [Ca(2)](c) 静息水平和从7.5到6.0的细胞内酸化，两者均取决于浓度。细胞外钙和来自细胞内细胞器的钙都是瞬时第二个胞质钙峰的来源，对于用0.1毫米胺碘酮处理的细胞，其振幅为0.12 μ m。在P型atp酶缺陷型黑曲霉菌株pmrAΔ 和pmca Δ 中，胺碘酮处理后的 [Ca(2)](c) 静息水平至少是野生型的两倍，这与真菌活力和对胺碘酮的超敏反应有关。胺碘酮和两性霉素b的组合在细胞活力和胞质钙内流方面是累加的。相反，唑类药物和胺碘酮的组合对真菌的生存能力具有协同作用。

BACKGROUND & AIMS: :The potent and efficacious anti-dysrhythmic agent amiodarone (AM) can cause potentially life-threatening lung damage (amiodarone-induced pulmonary toxicity; AIPT), which is characterized by cell death in the lungs, followed by inflammation and fibrosis. AM's major metabolite, desethylamiodarone (DEA), has a greater toxic potency than AM and it has been suggested that DEA may act synergistically with AM to cause lung toxicity. The objective of this study was to determine the type of cytotoxic interaction between AM and DEA in HPL1A human peripheral lung epithelial cells. Cytotoxicity was measured by lactate dehydrogenase release. AM and DEA caused concentration-dependent cytotoxicity in HPL1A cells. The concentration of drug causing 50% cell death (LC50) and the Hill slope factor, which represents steepness of the concentration-cell death curve, were significantly different between AM and DEA (12.4μM and 1.98; 5.07μM and 5.43, for AM and DEA, respectively) indicating that they may induce cytotoxicity through different mechanisms. A combined concentration of 7.13μM AM plus DEA, equivalent to 41% of each compound's individual LC50 value, resulted in 50% cell death. Isobolographic analysis revealed this effect to be additive, although the combined concentrations were only slightly higher than the concentrations that defined the threshold of synergy (threshold of synergy=4.21±1.98μM AM plus 1.73±1.05μM DEA; experimental data point=5.06±0.47μM AM plus 2.07±0.47μM DEA). The cytotoxic interaction between AM and DEA may be clinically relevant in the development of AIPT.

背景与目标： : 有效且有效的抗心律不齐剂胺碘酮 (AM) 可引起潜在的威胁生命的肺损伤 (胺碘酮诱导的肺毒性; AIPT)，其特征是肺中的细胞死亡，随后是炎症和纤维化。AM的主要代谢产物去乙基胺碘酮 (DEA) 比AM具有更大的毒性，并且有人建议DEA可能与AM协同作用以引起肺毒性。这项研究的目的是确定HPL1A人周围肺上皮细胞中AM和DEA之间的细胞毒性相互作用的类型。通过乳酸脱氢酶释放来测量细胞毒性。AM和DEA在HPL1A细胞中引起浓度依赖性的细胞毒性。引起50% 细胞死亡的药物浓度 (LC50) 和代表浓度-细胞死亡曲线陡度的希尔斜率因子在AM和DEA之间存在显着差异 (12.4 μ m和1.98; 5.07 μ m和5.43，对于AM和DEA，分别) 表明它们可能通过不同的机制诱导细胞毒性。7.13 μ m AM加上DEA的组合浓度，相当于每种化合物的单独LC50值的41%，导致50% 细胞死亡。等射线照相分析显示这种效应是累加的，尽管组合浓度仅略高于定义协同作用阈值的浓度 (协同作用阈值 = 4.21 ± 1.98 μ m AM加1.73 ± 1.05 μ m DEA; 实验数据点 = 5.06 ± 0.47 μ m AM加2.07 ± 0.47 μ m DEA)。AM和DEA之间的细胞毒性相互作用可能与AIPT的发展有关。

BACKGROUND & AIMS: AIM:To investigate the interactions at a metabolic level between lovastatin, amiodarone and carbon tetrachloride in isolated rat hepatocytes. METHODS:For cell isolation two-step collagenase liver perfusion was performed. Lovastatin was administered alone in increasing concentrations (1 mumol/L, 3 mumol/L, 5 mumol/L and 10 mumol/L) and in combination with CCl(4) (86 mumol/L). The cells were also pretreated with 14 mumol/L amiodarone and then the other two compounds were added. RESULTS:Lovastatin promoted concentration-dependent significant toxicity estimated by decrease in cell viability and GSH level by 45% and 84%, respectively. LDH-activity increased by 114% and TBARS content by 90%. CCl(4)induced the expected severe damage on the examined parameters. CCl(4) induced toxicity was attenuated after lovastatin pretreatment, which was expressed in less increased values of LDH activity and TBARS levels, as well as in less decreased cell viability and GSH concentrations. However, the pretreatment of hepatocytes with amiodarone abolished the protective effect of lovastatin. CONCLUSION:We suggest that the observed cytoprotective effect was due to interactions between lovastatin, CCl(4) and amiodarone at a metabolic level.

背景与目标：

BACKGROUND & AIMS: :Junctional ectopic tachycardia (JET) occurs most frequently after operative repair of congenital heart defects. The mechanism is thought to involve direct trauma to the atrioventricular node and His bundle resulting in an ectopic focus. Several therapeutic methods have been described in the pediatric literature with varying degrees of success and complication rates. Because heart rates may exceed 200 to 300 beats per minute, there may be inadequate time for ventricular filling. Ventricular filling can be further compromised because of the asynchrony between the atria and the ventricles. These factors can lead to significant compromise of cardiovascular function in the postoperative patient. We describe our experience with amiodarone in two patients who developed postoperative JET after repair of congenital heart defects. Dosing regimens and previous experience with amiodarone in patients with JET are reviewed.

背景与目标： : 先天性心脏缺损的手术修复后，交界性异位心动过速 (JET) 最常见。该机制被认为涉及对房室结及其束的直接创伤，导致异位灶。儿科文献中已经描述了几种治疗方法，其成功率和并发症发生率不同。因为心率可能超过每分钟200到300次，所以心室充盈的时间可能不足。由于心房和心室之间的不同步，可以进一步损害心室充盈。这些因素可能会导致术后患者的心血管功能显着受损。我们描述了两名在先天性心脏缺损修复后出现术后喷射的患者中使用胺碘酮的经验。回顾了JET患者的给药方案和以前使用胺碘酮的经验。

BACKGROUND & AIMS: :The binding of [3H]digoxin to purified canine cardiac sarcolemmal vesicles was characterized. Scatchard analysis of saturation isotherms yielded linear plots with a maximal binding capacity of 174 +/- 31.9 pmol/mg, a dissociation constant of 31.7 +/- 4.59 nM, and a Hill coefficient of 0.947 +/- 0.02 (mean +/- SEM), suggesting that [3H]digoxin bound to a single class of sites. In contrast to their marked effect on steady-state serum digoxin levels when administered in combination, quinidine, verapamil, and amiodarone were without effect on equilibrium binding of [3H]digoxin. Thus, increased steady-state serum concentrations of digoxin resulting from combination therapy with these particular drugs probably will have cardiac effects that may increase the risk of digitoxicity to the patient.

背景与目标： : 表征了 [3H] 地高辛与纯化的犬心脏肌膜囊泡的结合。饱和等温线的Scatchard分析得出线性曲线，最大结合能力为174/- 31.9 pmol/mg，解离常数为31.7/- 4.59 nM，和0.947 +/- 0.02的希尔系数 (平均值 +/- SEM)，表明 [3H] 地高辛结合到单一类别的位点。与联合给药时它们对稳态血清地高辛水平的显著影响相反，奎尼丁，维拉帕米，胺碘酮对 [3H] 地高辛的平衡结合没有影响。因此，与这些特定药物联合治疗导致地高辛的稳态血清浓度增加可能会产生心脏效应，这可能会增加患者的数字化风险。

BACKGROUND & AIMS: OBJECTIVE:To examine the efficacy of bolus dose intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained monomorphic ventricular tachycardia (VT). DESIGN, SETTING AND PARTICIPANTS:Retrospective case series of consecutive emergency admissions with haemodynamically-tolerated sustained monomorphic VT administered bolus dose intravenous amiodarone 300 mg, according to current UK advanced life support practice guidelines. MAIN OUTCOME MEASURES:Pharmacological termination rates within 20 min and 1 h and incidence of hypotension requiring emergency direct current cardioversion (DCCV) during this period. RESULTS:41 patients (35 men) of mean (SD) age 68 (10) years, the majority (85%) with ischaemic heart disease and impaired left ventricular function (mean (SD) ejection fraction 0.31 (0.11)), were enrolled in the study. The median VT duration was 70 min (range 15-6000), mean heart rate was 174 (34) bpm and systolic and diastolic blood pressures were 112 (22) and 73 (19) mm Hg, respectively. Pharmacological VT termination occurred within 20 min in 6/41 patients (15%; 95% CI 7% to 29%) and within 1 h in 12/41 patients (29%; 95% CI 18% to 45%). Haemodynamic deterioration requiring emergency DCCV occurred in 7/41 patients (17%; 95% CI 8% to 32%). CONCLUSIONS:Although advocated by advanced life support guidelines, bolus dose intravenous amiodarone was relatively ineffective for acutely terminating haemodynamically-tolerated sustained monomorphic VT with a significant incidence of haemodynamic destabilisation requiring emergency DCCV. Previous studies in the identical clinical setting suggest that alternative antiarrhythmic agents, particularly intravenous procainamide and sotalol, may be superior. A prospective randomised trial is required to determine the optimal drug treatment for stable sustained monomorphic VT in the emergency setting.

背景与目标：

BACKGROUND & AIMS: A woman who had been taking amiodarone--400 mg/day--for over nine years, developed cirrhosis. Electron microscopy showed phospholipid-laden lysosomal lamellar bodies containing myelin figures. A review is made about the reported cases of amiodarone-induced cirrhosis, including detailed histological findings. We conclude that periodical clinical and biochemical monitoring must be made in patients receiving treatment with amiodarone, and that the pathophysiologic mechanism responsible for the amiodarone toxicity still remains unclear.

背景与目标： 一名服用胺碘酮 (400毫克/天) 超过9年的妇女发展为肝硬化。电子显微镜显示载有磷脂的溶酶体层状体含有髓鞘图。对胺碘酮引起的肝硬化的报道病例进行了综述，包括详细的组织学发现。我们得出的结论是，必须对接受胺碘酮治疗的患者进行定期的临床和生化监测，并且导致胺碘酮毒性的病理生理机制仍不清楚。