开启心力衰竭治疗的新纪元——3类神经激素拮抗剂的应用

以往心力衰竭(心衰)神经激素拮抗治疗主要阻止交感神经系统(SNS)和肾素-血管紧张素-醛固酮系统(RAAS)两个系统的致病作用,降低心衰死亡风险。保护利钠肽系统(NPS)的血管紧张素受体脑啡肽酶抑制剂(ARNI)阻止利钠肽降解,进一步降低全因死亡风险16%,开启了3类系统神经激素拮抗剂治疗心衰的新时代。指南推荐射血分数下降的心衰(HFrEF)患者使用血管紧张素转化酶抑制剂(ACEI)或血管紧张素Ⅱ受体拮抗剂(ARB)或ARNI,联合β受体阻滞剂,部分患者合用醛固酮拮抗剂,减少心衰的发病率及病死率。     

《2022年美国心力衰竭管理指南》十大更新要点

2022-04-02,美国心脏协会(AHA)、美国心脏病学会(ACC)与美国心力衰竭学会(HFSA)联合颁布了《2022年美国心力衰竭管理指南》,现总结其更新要点如下。1对射血分数降低的心力衰竭(HFrEF)推荐的基础药物包括4类,除既往指南推荐的血管紧张素受体脑啡肽酶抑制剂(ARNI)/血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体阻滞剂(ARB)、β-受体阻滞剂(BB)和盐皮质激素受体拮抗剂(MRA)3大类药物外,对近年来经随机化临床研究证实有效的钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)也做出了重要推荐。     

慢性心力衰竭患者住院期间药物使用情况分析

目的分析慢性心力衰竭(CHF)患者住院期间利尿剂、β受体阻滞剂、血管紧张素转换酶抑制剂(ACEI)及/或血管紧张素Ⅱ受体拮抗剂(ARB)及洋地黄药物的使用情况。方法收集我院心内科2009年1月—2010年12月住院的223例CHF患者,将其分为收缩性心力衰竭(SHF)、舒张性心力衰竭(DHF)及混合性心力衰竭三类,并对三类患者住院期间药物使用情况进行回顾性分析。结果患者以接受利尿剂治疗居多,静脉制剂以呋塞米及托拉塞米为主,约占70%,螺内酯为主要的口服制剂。SHF、DHF及混合性心力衰竭患者中药物使用情况分别为:血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体拮抗剂(ARB)占70.6%、71.0%、71.2%;β受体阻滞剂占56.3%、58.1%、49.3%;洋地黄占68.9%、19.4%、61.6%;β受体阻滞剂以美托洛尔为主,占74%,平均剂量平片(10.9±5.4)mg,缓释片(18.1±6.8)mg。结论慢性心力衰竭患者住院期间ACEI、ARB、β受体阻滞剂、洋地黄四类药物使用广泛,总有效率达92.4%,需进一步加强β受体阻滞剂及ACEI/ARB的应用,有助于改善预后。     

ACEI与ARB联用治疗心衰的临床评价

血管紧张素转换酶抑制剂 (ACEI)已经成为治疗心力衰竭的基本用药 ,血管紧张素II受体阻滞剂(ARB)也已经应用于心力衰竭的治疗。两者作用机制的异同点促使人们思考联合应用ACEI与ARB的临床价值及可行性 ,近年来一些大型的临床试验试图给出明确的答案 ,却给人们提出了更多的问题     

心力衰竭病人β-受体阻滞剂、血管紧张素转化酶抑制剂的应用与血管紧张素Ⅱ水平

本研究旨在弄清心力衰竭应用血管紧张素转化酶抑制剂 (ＡＣＥＩ)的病人同时应用 β 受体阻滞剂是否可以降低病人血液血管紧张素Ⅱ水平。方法　研究对象为Ａｌｆｒｅｄ医院心脏中心的心力衰竭病人。心功能为Ⅱ～Ⅲ级 (ＮＹＨＡ标准 )。所有病人均接受最大耐受剂量ＡＣＥＩ治疗 ,测定病人用药治疗前、后血管紧张素水平。1 1例未用β 受体阻滞剂病人为Ａ组 ,1 1例应用最大耐受剂量β 受体阻滞剂病人为Ｂ组。于心导管检查时采集血样。Ａ组 1 0例、Ｂ组 9例应用襻利尿剂治疗。两组各有 3例应用了安体舒通治疗。Ａ组 7例应用卡托普利 2 5～1 0 0ｍ…     

倍他乐克对接受卡托普利治疗的充血性心衰病人血管紧张素Ⅱ的影响

目的探讨β受体阻滞剂对应用血管紧张素转换酶抑制剂(ACEI)治疗的充血性心力衰竭(CHF)病人血管紧张素Ⅱ的影响.方法对比应用卡托普利治疗组(A组)与卡托普利合用倍他乐克治疗组(B组)的血管紧张素Ⅱ水平.结果A组血管紧张素Ⅱ升高的发生率明显高于B组(P＜0.05).结论提示β受体阻滞剂降低CHF病人的血管紧张素Ⅱ升高的发生率,是其降低CHF病人死亡率的重要原因之一.     

培朵普利与卡维地洛联合应用治疗充血性心力衰竭

目的　观察血管紧张素转换酶抑制剂 (ACEI)培朵普利和非选择性 β 受体阻滞剂卡维地洛联合应用治疗慢性充血性心力衰竭 (CHF)患者的临床疗效。方法　采用培朵普利和卡维地洛联合治疗CHF患者 34例 ,并与单用培朵普利治疗 30例进行比较。结果　治疗组与对照组的有效率分别为 94 1%和 70 % (P <0 0 5 )。结论　ACEI及非选择性β 受体阻滞剂卡维地洛联合应用是治疗慢性充血性心力衰竭安全有效的方法     

β受体阻滞剂联合ARBs在老年重症心力衰竭患者中的治疗效果

目的探讨β受体阻滞剂联合血管紧张素Ⅱ受体拮抗剂(ARBs)在老年重症心力衰竭患者中的临床效果。方法回顾性分析80例老年重症心力衰竭患者的临床资料,按照治疗方法分为对照组和观察组各40例,观察两组心功能转归情况。结果观察组心功能等级评分(NYHA)和血清脑钠肽(BNP)及左室射血分数(LVEF)改善情况均显著优于对照组(均P<0. 05)。结论β受体阻滞剂联合ARBs治疗老年重症心力衰竭患者可以获得良好的临床效果,显著改善患者的心功能等。     

心力衰竭新临床试验的意义与评价

近年对心力衰竭(heart failure,HF)研究的重点是寻找血管紧张素受体拮抗剂(angiotensin receptor blocker,ARB)与血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitors,ACEI)的比较及联合应用、非选择性β受体阻滞剂与β1受体阻滞剂比较和新开发的选择性醛固酮受体拮抗剂的新证据.近年公布的几项具有重要影响意义的HF药物治疗临床试验,反映了HF药物治疗的进展,并回答了有关HF治疗中人们关注的问题.     

血管紧张素Ⅱ受体阻滞剂与神经保护

血管紧张素Ⅱ受体阻滞剂(ARB)通过阻滞1型血管紧张素Ⅱ受体(AT1受体)降低血压、逆转血管重构,激活2型血管紧张素Ⅱ受体(AT2受体)以提高血管紧张素Ⅱ(AngⅡ)水平扩张血管、抗增殖及调脂.进一步了解ARB在神经保护中的作用机制,可为临床治疗缺血性卒中提供新的思路.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.