决奈达隆治疗心房颤动的现状及展望

决奈达隆是治疗心房颤动的新药之一,该药与传统胺碘酮具有类似的药理作用,但它不含碘,故不会引起与碘相关的不良反应。对于决奈达隆治疗心房颤动的有效性和安全性已经进行了广泛的临床研究,现就决奈达隆的临床现状及临床新进展做一简述,为临床用药提供指导。     

决奈达隆的电生理与临床应用进展

决奈达隆是非碘化的苯并呋喃衍生物，其化学结构与胺碘酮类似。决奈达隆作为一种新型的抗心律失常药物，具有多通道阻滞的作用，它既保留了胺碘酮的疗效，又具有更高的安全性。其有效性和安全性经多个临床试验证实后，于2009年被FAD批准用于心房颤动患者复律后窦性心律的维持。本文就决奈达隆的电生理与临床应用进展作扼要介绍。     

盐酸决奈达龙口服对兔左室肌电生理特性的影响

目的探讨决奈达龙口服后对新西兰大白兔左室楔形心肌组织块电生理特性的影响。方法 20只兔随机分为对照组和决奈达龙组,对照组给予正常饮食,决奈达龙组给予正常饮食和决奈达龙100 mg·kg-1·d-1,连续4周。4周后建立冠状动脉灌注的兔左室楔形心肌组织块模型,应用浮置玻璃微电极和心电图同步记录技术,观察两组内外两层心肌细胞的动作电位时程(APD)、跨壁复极离散度(TDR)及心律失常发生情况。结果在不同的刺激频率下(1 000、2 000、3 000、4 000),1决奈达龙组心肌细胞的QT间期较对照组延长(P0.05)。2决奈达龙组内、外膜心肌细胞的APD较对照组均延长(P均0.05)。3决奈达龙组心肌细胞的TDR较对照组缩短(P0.05)。结论决奈达龙可延长兔内、外膜心肌细胞的APD,并可减小心肌细胞的TDR。     

决奈达隆的特性和应用进展

正决奈达隆(dronedarone)是新型Ⅲ类抗心律失常药,由法国赛诺菲·安万特公司开发,于2009年相继在美国和欧洲上市。其化学结构类似胺碘酮(乙胺碘呋酮胺碘酮)但不含碘,既有与胺碘酮相似的电生理作用,又摒除了碘相关不良反应,因而备受推崇。然而,随着临床试验结果的不断报告,曾为人们看好的决奈达隆治疗慢性心力衰竭(心衰)和急性心肌梗死的探索提前终止。其适应证仅限于心房颤动(房颤)转复之后窦性心律的维持。当下决奈达隆的路在何方仍     

文摘

决奈达隆治疗充血性心衰疗效评价 决奈达隆主要用于治疗房颤（AF）和诸种室上性或室性心律失常等。然而晚近报道称，至少在新发失代偿性充血性心衰（CHF）和左室功能不全者，该药可能将过度增高死亡风险。本文特就决奈达隆用于防治CHF并发AF者的死亡率和并发症等远期综合药效进行了大样本调查分析。     

新药决奈达隆

决奈达隆是一种多通道阻滞剂,与胺碘酮一样,兼具Ⅰ～Ⅳ类抗心律失常药物(Vaughan-Williams分类)的特性。药理学研究中,决奈达隆的电生理学和血液动力学特性与胺碘酮相似。动物模型研究显示,     

如何看待关于决奈达隆的不同信息

近来,有关新的抗心律失常药决奈达隆( dronedarone)信息引起了许多关注,其临床疗效与安全性、适应证与禁忌证已经陆续有报道,但也有上市后发现副作用和有关其临床试验(PALLAS研究)被提前终止的消息.该药品尚未在我国上市,如何看待这一新药却已经成为一个较为热门的话题.盐酸决奈达隆是苯并呋喃的一种衍生物,结构类似于胺碘酮,但不含有碘,且增加了一个甲基磺胺基团.因此,决奈达隆的组织内蓄积减少,理论上对器官的毒性降低.其细胞电生理研究显示,该药的作用类似胺碘酮.     

导管消融术后早期使用决奈达隆对房颤及房扑复发的预防效果

目的:研究导管消融术后早期使用决奈达隆对房颤及房扑复发的预防效果.方法:于我院行导管消融术进行肺静脉隔离术的256例阵发性房颤/房扑患者被随机均分为胺碘酮组(在常规治疗基础上加用胺碘酮口服200mg,1次/d)与决奈达隆组(在常规治疗基础上加用决奈达隆口服400mg,2次/d),两组出院后均治疗3个月,停药后再随访9个...     

决奈达隆用于心房颤动导管消融术后空白期疗效的临床研究

目的:探讨决奈达隆与胺碘酮对心房颤动导管消融术后空白期维持窦性心律的疗效与安全性。方法:收集2019年5月至2020年10月我科收治的98例接受导管射频消融术治疗的阵发性和持续性心房颤动患者。按照术后使用抗心律失常药物的类型,患者被随机分为决奈达隆组(52例)和胺碘酮组(46例)。比较两组术后3月内房颤复发发生率、术后1月、3月QTc变化,以及不良反应发生率。结果:术后随访3个月内,决奈达隆组房颤复发率显著高于胺碘酮组(26.9%比10.9%),P=0.045。与术前比较,两组术后1个月、3个月的QTc均显著延长[决奈达隆组:(423.9±40.0)ms比(439.6±37.7)ms比(441.6±38.7)ms,胺碘酮组:(422.2±29.8)ms比(447.5±30.2)ms比(447.6±23.1)ms],P均<0.01;该不同时间点,两组间QTc均无显著差异,P均>0.05。决奈达隆组总的不良反应发生率显著低于胺碘酮组(26.9%比47.9%),P=0.032。结论:房颤导管消融术后3个月空白期内,决奈达隆维持窦律疗效不如胺碘酮,而总的不良反应率显著低于胺碘酮。     

决奈达隆与胺碘酮维持房颤者窦律疗效比较

决奈达隆系不含碘的胺碘酮衍生物之一，据报道其维持房颤（AF）者窦律药效较佳。然而既往关于决奈达隆与胺碘酮两者在维持复发AF者AF复发及窦律中的有效性和安全性尚无直接两相比较对照研究，本文就此进行了汇总分析。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.