胺碘酮诱发甲状腺功能亢进症32例临床分析

目的:探讨胺碘酮诱发的甲状腺功能亢进症(AIT)的临床进程和预后因素.方法:回顾性分析我院32例有完整资料的胺碘酮诱发的甲状腺功能亢进症患者,对其,临床特征、实验室参数、治疗方法和随访过程中的事件发生率进行评估,以和AIT相关的并发症如:死亡、心衰住院、中风、心律失常等作为观察终点.结果:32例病人中有1l例接受强的松治疗,但血清游离甲状腺素恢复正常的时间和非强的松治疗组比较没有差异,长期随访结果显示强的松治疗组具有较高的事件发生率.结论:胺碘酮诱发甲状腺亢进症具有较高的事件发生率,强的松治疗不能缩短血清甲状腺素恢复正常时间,反而增加不良事件发生率.     

胺碘酮联合厄贝沙坦对慢性心功能不全合并阵发性房颤的临床效果观察

目的:评价胺碘酮联合厄贝沙坦治疗慢性心功能不全合并阵发性房颤的临床疗效及安全性.方法:选择我院收治的慢性心衰合并阵发性房颤患者167例,均使用胺碘酮维持窦性心律,根据患者是否加用厄贝沙坦分为治疗组及对照组.治疗一年后,观察和比较两组患者的心衰住院率、左室射血分数、左房内径、心功能分级情况,通过动态心电图评估窦性心律维持率、房颤复发率.结果:治疗后,治疗组房颤的复发率、慢性房颤的发生率均明显低于对照组,窦性心律维持率明显高于对照组,左房内径较对照组明显减小,心衰住院率明显低于对照组,差异均有统计学意义(P＜0.05);对照组左房内径较治疗前明显扩大(P＜0.05),两组患者在心功能分级方面较治疗前均有明显改善(P＜0.05),但两组之间心功能分级比较无统计学差异(P＞0.05).两组不良反应(甲状腺功能异常、肝功能异常、肺纤维化、低血压)的发生率比较无统计学差异(P＞0.05).结论:胺碘酮联合厄贝沙坦治疗慢性心功能不全伴阵发性房颤的患者,能较好的维持窦性心律,降低心衰住院率,对心脏重构有较好的改善作用,且具有良好的安全性.     

胺碘酮与普罗帕酮在快速性心律失常患者院前急救效果中的对比研究

摘要 目的：对比胺碘酮与普罗帕酮在快速性心律失常患者院前急救中的临床效果。方法：将石家庄市急救中心 2019年 4月~2021年 2月期间院前急救时现场治疗的快速性心律失常患者（n=108）按照随机数字表法分为对照组（n=54）和观察组（n=54）。对照组接受普罗帕酮治疗,观察组接受胺碘酮治疗,比较两组心功能、血压、心率（HR）、炎症因子指标、心肌损伤指标及不良反应发生率。结果：治疗结束后,观察组左心室射血分数（LVEF）、心输血量（CO）、二尖瓣舒张早期 /晚期峰值流速（E/A）均高于对照组（P<0.05）。治疗结束后,观察组收缩压（SBP）、舒张压（DBP）、HR均低于对照组（P<0.05）。治疗结束后,观察组肿瘤坏死因子 -α（TNF-α）和白介素 -6（IL-6）水平均低于对照组（P<0.05）。治疗结束后,观察组心肌肌钙蛋白Ⅰ（cTnI）、脑钠肽（BNP）、肌酸激酶同工酶（CK-MB）水平均低于对照组（P<0.05）。两组不良反应发生率组间对比无统计学差异（P>0.05）。结论：在快速性心律失常患者院前急救中,相比于普罗帕酮,胺碘酮可有效改善患者心功能,减少心肌损伤,恢复血压并改善 HR,减轻炎症反应。     

Use of an antiarrhythmic drug against acute selenium toxicity

ObjectiveSelenium is an essential trace element. But, selenium may have toxic effects in high doses. There are no proven antidotes or curative treatments for acut selenium toxicity. Treatment involves stopping the exposure and providing supportive care for symptoms. Therefore, it is necessary to find more effective substances in the treatment of selenium toxicity. The aim of this study was to increase the survival rate of animals by supporting the heart with amiodarone and to determine the effect of amiodarone on the pathological, hematological and biochemical parameters in acute selenium intoxication.Methods64 Wistar-Albino rats were divided into four groups. Group I was given only distilled water, Group II was given 18 mg/kg dose of amiodarone, Group III was given 18 mg/kg amiodarone and 10 mg/kg sodium selenite and Group IV was given sodium selenite 10 mg/kg (LD₅₀ dose)orally.Results11 of the 16 animals in Group IV died within the first 48 h of drug administration. However, no deaths were observed in the rats in Group III. No hematological changes were observed. Biochemically, CK, CK-MB and LDH levels of Group IV were higher than the other groups on both the 2nd and 10th days. In Groups II and III, this serum level decreased, and vitamin B12 levels increased. In macroscopic inspections of the organs of Groups III and IV, slight paleness was detected. Histopathologically, degenerative changes in tissue were observed, especially in Group IV.ConclusionThis study shows that amiodarone application has a reducing effect on selenium toxicity. This was because amiodarone protected the heart by reducing CK and CK-MB levels and increased vitamin B12 levels, which play a role in the synthesis of S-adenosyl methionine that converts selenium into a nontoxic form.     

68例服胺碘酮的75岁以上老年心律失常患者甲功变化分析

目的:探讨口服小剂量胺碘酮对老年心律失常患者甲状腺功能的作用和影响。方法:回顾性分析老年器质性心脏病心律失常患者68例,记录胺碘酮治疗方案与疗效、甲状腺变化及随访干预措施情况。结果:老年人服用胺碘酮引起甲状腺疾病发生率为31.8%(22/68),以甲状腺功能减退25.7%(18/68)为主,大致为甲状腺功能亢进(6.1%,4/68)的4倍。采用小剂量胺碘酮方案出现的甲状腺功能紊乱多数经过减量或停药逆转或恢复。结论:老年人服用胺碘酮甲状腺功能紊乱发生率高,但临床表现不典型,应更密切地监测甲状腺功能;甲状腺功能紊乱经胺碘酮及时减量或停药等措施多能逆转或恢复。     

胺碘酮致甲状腺功能异常的诊治进展

胺碘酮是治疗心律失常的常用药物。但由于其富含碘及自身固有的特性,可导致一系列甲状腺功能的紊乱,甚至引发明显的甲状腺功能减退（甲减）或甲状腺功能亢进（甲亢）。对于胺碘酮所致甲减（AIH）的诊断和治疗目前比较清晰,但对胺碘酮所致甲亢（AIT）的诊断、鉴别其亚型及治疗有一定的难度。     

68例服胺碘酮的75岁以上老年心律失常患者甲功变化分析

目的：探讨口服小剂量胺碘酮对老年心律失常患者甲状腺功能的作用和影响。方法：回顾性分析老年器质性心脏病心律失常患者68例,记录胺碘酮治疗方案与疗效、甲状腺变化及随访干预措施情况。结果：老年人服用胺碘酮引起甲状腺疾病发生率为31．8％（22／68）,以甲状腺功能减退25．7％（18／68）为主,大致为甲状腺功能亢进（6．1％,4／68）的4倍。采用小剂量胺碘酮方案出现的甲状腺功能紊乱多数经过减量或停药逆转或恢复。结论：老年人服用胺碘酮甲状腺功能紊乱发生率高,但临床表现不典型,应更密切地监测甲状腺功能;甲状腺功能紊乱经胺碘酮及时减量或停药等措施多能逆转或恢复。     

Late-onset thyrotoxicosis after the cessation of amiodarone

IntroductionAmiodarone is a highly effective antiarrhythmic-drug with well recognized toxic side-effects. The effects of the drug late in patients with atrial fibrillation (AF) is not well described.Methods and resultsWe present a single centre prospectively collected series of patients with thyrotoxicosis occurring late after the cessation of amiodarone. Between 2006 and 2018, 8 patients were identified with amiodarone induced thyrotoxicosis (AIT). Amiodarone was prescribed for AF in 7 patients and ventricular tachycardia in 1 patient. Mean duration of therapy was 329 [42–1092] days, mean dose of 200 ± 103.5 mg/day. Amiodarone use was short term (<140 days) in 4 of the 8 cases, with one treated for 42 days. Patients presented with symptoms including weight loss, tremors, palpitations, AF, sweats all indicative of AIT at a median of 347 [60–967] days post cessation. Thyroid function testing confirmed suppressed thyroid stimulating hormone and elevated T levels in all patients. Nuclear thyroid imaging in all cases demonstrated low uptake of iodine indicative of Type II AIT. All patients recovered following pharmaceutical treatment with Carbimazole and Prednisolone.ConclusionsWe describe a series of patients with late thyrotoxicosis after exposure to amiodarone. Our findings highlight the need for a high-index of clinical suspicion for AIT regardless of treatment duration or time after cessation of amiodarone.     

Group XV phospholipase A₂, a lysosomal phospholipase A₂

A phospholipase A₂ was identified from MDCK cell homogenates with broad specificity toward glycerophospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. The phospholipase has the unique ability to transacylate short chain ceramides. This phospholipase is calcium-independent, localized to lysosomes, and has an acidic pH optimum. The enzyme was purified from bovine brain and found to be a water-soluble glycoprotein consisting of a single peptide chain with a molecular weight of 45 kDa. The primary structure deduced from the DNA sequences is highly conserved between chordates. The enzyme was named lysosomal phospholipase A₂ (LPLA₂) and subsequently designated group XV phospholipase A₂. LPLA₂ has 49% of amino acid sequence identity to lecithin-cholesterol acyltransferase and is a member of the αβ-hydrolase superfamily. LPLA₂ is highly expressed in alveolar macrophages. A marked accumulation of glycerophospholipids and extensive lamellar inclusion bodies, a hallmark of cellular phospholipidosis, is observed in alveolar macrophages in LPLA₂^−/− mice. This defect can also be reproduced in macrophages that are exposed to cationic amphiphilic drugs such as amiodarone. In addition, older LPLA₂^−/− mice develop a phenotype similar to human autoimmune disease. These observations indicate that LPLA₂ may play a primary role in phospholipid homeostasis, drug toxicity, and host defense.     

High affinity HERG K(+) channel blockade by the antiarrhythmic agent dronedarone: resistance to mutations of the S6 residues Y652 and F656

Pharmacological inhibition of human-ether-a-go-go-related gene (HERG) K(+) channels by structurally and therapeutically diverse drugs is associated with the 'acquired' form of long QT syndrome and with potentially lethal cardiac arrhythmias. Two aromatic amino-acid residues (Y652 and F656) on the inner (S6) helices are considered to be key constituents of a high affinity drug binding site within the HERG channel pore cavity. Using wild-type (WT) and mutant HERG channels expressed in mammalian cell lines, we have investigated HERG channel current (I(HERG)) blockade at 37+/-1 degrees C by dronedarone (DRONED), a non-iodinated analogue of the Class III antiarrhythmic agent amiodarone (AMIOD). Under our conditions WT I(HERG) tails, measured at -40 mV following activating pulses to +30 mV, were blocked with IC(50) values of approximately 59 and 70 nM for DRONED and AMIOD, respectively. I(HERG) inhibition by DRONED was contingent upon channel gating, with block developing rapidly on membrane depolarization, but with no preference for activated over inactivated channels. High external [K(+)] (94 mM) reduced the potency of I(HERG) inhibition by both DRONED and AMIOD. Strikingly, mutagenesis to alanine of the S6 residue F656 (F656A) failed to eliminate blockade by both DRONED and AMIOD, whilst Y652A had comparatively little effect on DRONED but some effect on AMIOD. These findings demonstrate that high affinity drug blockade of I(HERG) can occur without a strong dependence on the Y652 and F656 aromatic amino-acid residues.