复苏时需用钙剂吗?

心肌兴奋收缩偶联需有Ca~(++)参与,而Ca~(++)能增强心肌收缩力,心停搏时Ca~(++)能提高心室自律性,但心肺复苏时是否用钙争论较多。本文通过介绍钙对心肌的作用,心源性和败血症性休克时有关钙的研究以及心停搏时用钙的问题等方面对钙应用的利弊进行了讨论。     

左西孟旦在心脏外科手术的应用

心脏外科手术中体外循环后心功能障碍的病人常需要正性肌力药物的支持.传统的正性肌力药由于存在增加心肌氧耗和致心律失常的危险,临床应用受到一定限制.左西孟旦,一种新型强心剂-钙增敏剂,其强心作用机制是增加心肌收缩蛋白对钙离子的敏感性,并通过激活KATP发挥扩血管和抗缺血效应.现有的临床资料表明左西孟旦在治疗术中高危或合并左心功能不全的心脏手术病人以及帮助病人顺利脱离体外循环方面具有很好的应用前景.     

钙拮抗药在麻醉中作为降压药应用的进展

临床上虽有多种降压药,由于各种降压药的作用机理不同,与麻醉药之间的相互作用可给病人带来危险。而钙拮抗药的降压效果好,对心肌抑制少,在麻醉过程中作为降压药比较理想。一、降压作用机制钙拮抗药能特异性地抑制细胞外钙穿过细胞膜和钙离子从肌浆网的结合部位进入细胞浆,从而抑制平滑肌收缩,使心脏收缩降低,冠状动脉和体循环血管扩张。由于血管平滑肌松弛,末梢血管扩张,血压下降,并使去甲肾上腺素和血管紧张素Ⅱ等反应性减弱,从而起到降压效果。     

异氟醚对循环功能的影响

异氟醚是一种含卤素的新吸入麻醉药,与安氟醚和氟烷相比,对循环功能影响较轻,用于心脏代偿能力较差的患者,较安氟醚和氟烷为安全。一、异氟醚对心脏功能的影响 1.异氟醚对心肌收缩力的影响异氟醚抑制离体心肌的收缩力,其对心肌缩短的最大速率和平均最大上升力的抑制     

大鼠严重烧伤早期心肌局部肾素-血管紧张素系统的变化

心脏存在有独立的肾素一血管紧张素系统(RAS),心脏可自身合成、释放肾素、血管紧张素。与循环RAS不同,心脏局部RAS只作用于心脏局部,主要参与心肌局部血流量和血管紧张性的调节,也参与心肌收缩力的调节。心脏局部RAS在维持心血管正常功能活动及参与心血管疾病的发生、发展过程中起着不容忽视的作用。我们动态观察了大鼠烧伤后心肌局部RAS的变化,并对其病理生理意义进行了探讨。     

钙与心搏骤停

美国国家心肺复苏和心脏急症抢救联合会和美国心脏协会过去一直推荐心搏骤停时使用氯化钙。主要是钙能增强心肌收缩力和自动性。Ca~(++)释入胞液(Cytosol)即引起心肌收缩。手术时低温停跳再灌注后注CaCl_2能刺激心脏收缩。但是,有些情况下,心搏骤停用CaCl_2对心脏正常收缩功能的恢     

在心脏手术中异氟醚的应用

异氟醚是二次大战以后最近问世的氟化吸入麻醉药。经动物和临床验证结果提示它比其他药物为好。在需要保护心肌和心排出量(CO)的心脏手术病人中,应用低浓度异氟醚有特殊的优点。一、异氟醚的心血管效应1.心肌状态(myocardial performance):它的浓度一旦超过2％,则导致与剂量相关的极为严重的抑制,这种效应方式与氟烷、安氟醚等吸入麻醉相似。它对心肌收缩力的抑制可能是通过降低CGMP的水平和/或降低收缩蛋白的钙活性。与氟烷或安氟醚不同之     

氨联吡啶酮用于心脏术后低心排综合征的治疗

氨联吡啶酮作为磷酸二酯酶抑制药,可减少cAMP降解,提高心肌细胞内cAMP浓度。其结果为一方面增强心肌收缩力,另方面促使心肌舒张完全,增加心室充盈和心排血量,同时还扩张动静脉血管,减轻心脏前后负荷,降低心脏作功。临床应用证实其对CABG等心脏术后低心排综合征的疗效较儿茶酚胺类正性肌力药更为理想。     

缺氧过程中DADLE对心肌收缩力和收缩长度的影响

目的通过建立人心室肌缺氧模型，研究DADLE[delta opioid peptide（D—Ala2，D—Leu5）enkephalin]对心肌的保护作用。方法15例标本均来自体外循环心脏手术患者的心肌组织，将其随机分成两组：组1（6例），为单纯缺氧；组2（9例），为缺氧条件下加入DADLE。实验第一步：两组均给氧，将心肌条浸浴在连续充入氧气的Tyrode’s灌注液中；第二步：组1用氮气代替氧气、组2氮气加DADLE（10nmool）代替氧气。在相应的刺激频率下测量心肌收缩力和收缩长度的变化并衡量DADLE的心肌保护作用。结果缺氧条件下无论是否给予DADLE，不同刺激频率下的心肌收缩力和心肌收缩长度都明显低于给氧状态下相应值（P〈0．05）；给氧时，如果组1、组2在15、20、30、45、60、90和120次／分刺激频率下的心肌收缩力和收缩长度为100％，缺氧时组2在相对应刺激频率下心肌收缩力和收缩长度的百分比明显高于组1，差异有统计学意义（P〈0．05）。结论DADLE在缺氧过程中对心肌收缩力和收缩长度有明显的影响，对心肌有一定的保护作用。     

兔心肌缺血预处理对异丙酚心肌负性肌力作用的影响

异丙酚对心肌收缩力的影响主要涉及两个方面:降低心肌细胞内钙离子浓度([Ca2 ]i),增强肌丝对钙的敏感性,产生心肌负性肌力作用。缺血预处理后,心肌细胞发生一系列病理生理变化,包括蛋白激酶C(PKC)激活,[Ca2 ]i下降,肌丝对钙的敏感性增高等。但是心肌缺血预处理对异丙酚心肌负性肌力作用的影响尚未定论。本实验拟观察心肌缺血预处理对异丙酚心肌负性肌力作用的影响,为临床研究提供参考。     

Levosimendan, a new inotropic and vasodilator agent

Several clinical studies suggest substantial limitations of currently available positive inotropic substances, including beta1-adrenoceptor agonists and phosphodiesterase III inhibitors in the short- and long-term treatment of heart failure. The reasons for these detrimental effects are related to the mechanism of action of these drugs, including increases in intracellular Ca2+ with subsequent increases in myocardial oxygen demand and arrhythmogenesis. Levosimendan, a myofilament Ca2+ sensitizer with inotropic effects, increases myocardial performance without substantial changes in oxygen consumption and with neutral effects on heart rhythm. In addition, levosimendan has vasodilatory effects that are achieved by stimulation of adenosine triphosphate-dependent potassium channels. This action may be of specific interest in the setting of myocardial ischemia. To date, levosimendan is approved in 31 countries worldwide, and more patients with heart failure have participated in randomized controlled trials with levosimendan than with any other intravenous inotropic agent.     

新型正性肌力药——左西孟旦

左西孟旦是钙离子增敏剂,并对KATP通道产生作用。它增强心肌收缩力而不增加心肌耗氧量;它还引起冠状动脉和体血管扩张。其药代动力学特点在健康人和在充血性心衰病人中相似。左西孟旦主要用于失代偿性急性心力衰竭和心肌顿抑。现就其药理学和临床应用效果作一综述。     

Inoprotection: the perioperative role of levosimendan

Levosimendan is emerging as a novel cardioprotective inotrope. Levosimendan augments myocardial contractility by sensitising contractile myofilaments to calcium without increasing myosin adenosine triphosphatase activity or oxygen consumption. Levosimendan activates cellular adenosine triphosphate-dependent potassium channels, a mechanism which is postulated to protect cells from ischaemia in a manner similar to ischaemic preconditioning. Levosimendan may therefore protect the ischaemic myocardium during ischaemia-reperfusion as well as improve the contractile function of the heart. Adenosine triphosphate-dependent potassium channel activation by levosimendan may also be protective in other tissues, such as coronary vascular endothelium, kidney and brain. Clinical trials in patients with decompensated heart failure and myocardial ischaemia show levosimendan to improve haemodynamic performance and potentially improve survival. This paper reviews the known pharmacology of levosimendan, the clinical experience with the drug to date and the potential use of levosimendan as a cardioprotective agent during surgery.     

左西孟旦乌司他丁与其联合用药对幼兔离体心脏的保护作用

目的 通过幼兔离体心脏Langendorff模型,探讨左西孟旦、乌司他丁及二者联合应用对幼兔离体心脏缺血再灌注损伤的保护作用.方法 建立新西兰幼兔离体心Langendorff模型,经左心房、二尖瓣置入左室测压管.K-H液平衡灌注10 min,分别用K-H液(C组)、乌司他丁5万单位/kg(U组)、小剂量左西孟旦0.1 μmoL/L(L1组)、大剂量左西孟旦0.3 μmol/L(L2 组)、乌司他丁5万单位/kg和左西孟旦0.1 μmol/L(L+U组)灌注10 min.应用St.Thomas停跳液使心脏停跳,全心缺血30 min,然后分别以上述液体复灌30 min.于缺血前和复灌即刻、10 min、20 min、30 min记录心率(HR)、左室内压(LVP)、左室内压最大上升速率(LVdp/dt)、冠脉流量(CF);同时测定冠状静脉流出液中肌酸激酶(CK)、肌钙蛋白(cTnI)、肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)的浓度.结果 L1 组、L2组和L+U组复灌后LVP、LVdp/dt与对照组(C组)和U组差异有统计学意义,但L2组的心率明显高于其他组.与其他各组比较,左西孟旦和乌司他丁联合用药组复灌后冠脉流量(CF)升高(P<0.05);冠状静脉流出液CK、cTnI,TNF-α、IL-6的浓度明显低于其他组.结论 左西孟旦和乌司他丁通过不同机制均能较好地减轻幼兔心肌缺血再灌注损伤,其联合用药对未成熟心肌的保护作用强于单独应用.

Abstract：

Objective Levosimendan,a new calcium ion sensitizer,is currently used in the treatment of heart failure and as an option for patients with injury to the left heart or at high risk for surgery.The study tried to evaluate the effects of levosimendan and ulinastain for protecting myocardium from ischemia-reperfusion (I/R) injury to the isolated immature rabbit hearts and investigate the possible mechanism.Methods Fifty New Zealand long-ear white immature rabbits were anesthetized and heparinized.Their hearts were rapidly removed and mounted on modified Langendorff apparatus.A left ventricle pressure monitoring line was inserted through the left atrial and mitral valve.The hearts were equilibrated with oxygenated K-H solution at 37℃ for 10 minutes.The rabbit hearts were randomly divided into 5 groups with 10 hearts in each group.Hearts in group C were perfused with K-H solution,in group U were perfused with ulinastain (50000 U/kg),in group LI were perfused with Levosimendan 0.1 μmol/L,in group L2 were perfused with Levosimendan 0.3 μmol/L,and in group L + U were perfused with Ulinastain (50 000 U/kg) and Levosimendan 0.1μmol/L.The hearts were arrested with St-Thomas solution for 30 min.Hearts in each group underwent 30 min-reperfusion with the same solutions after 30 min-global myocardial ischemia.Heart rate ( HR) Jeft ventricular pressure ( LVP) and LVdp/dtMax were monitored.Effluent from coronary sinus was collected at time of ischemia /reperfusion for measuring the concentration of TNF-α,IL-6,CK and cTnI.Results LVP and LVdp/dt in group L1,L2 and L + U were better than those in group C and U.But the heart rates in group L2 were higher than in other groups.Concentrations of CK,cTnI,TNF-α and IL-6 in the effluent from coronary sinus at 0、10 and 30 min of reperfusion were significantly lower in group L + U than in the other groups.Conclusion Levosimendan may have the similar effects with ulinastain in reducing the reperfusion injury to the immature myocardium.The protective effect of levosimendan (0.1 μmol/L) in combination with ulinastain (50 000 U/kg) was better than that of levosimendan or ulinastain alone.     

Levosimendan in septic shock: a case series

Editor—Levosimendan, a novel calcium sensitizer and K-ATPchannel opener, has been used in a variety of clinical settings,including acute decompensated and low output heart failure,adult respiratory distress syndrome, ischaemic myocardial stunning,and cardiac     

Levosimendan compared with dobutamine in low output patients

There are 2 studies which have investigated the hemodynamic efficacy of levosimendan compared to dobutamine in congestive heart failure patients. The first is a dose finding comparative 24-h infusion trial which included 95 NYHA II-III patients to different doses of levosimendan and 20 patients to dobutamine administered as a continuous, open-label infusion of 6 microg/kg/min. Efficacy and safety of levosimendan in severe low-output heart failure a randomized, double-blind comparison to dobutamine study compared the short- and long-term efficacy and safety of a single 24-hour infusion of levosimendan (n=103) with dobutamine (n=100) in hospitalised patients in acute heart failure. This double-blind, parallel-group, randomised trial showed that, irrespective of the aetiology of the heart failure, levosimendan produced significantly greater improvement in major determinants of cardiac function in heart failure patients compared to dobutamine. Levosimendan produced significantly greater haemodynamic improvements than dobutamine by significantly reduced mortality at 31 days compared with dobutamine; this reduction was maintained at 180 days. Levosimendan significantly increased the number of days alive and out of hospital, compared with dobutamine. It was better tolerated than dobutamine and fewer patients receiving levosimendan experienced arrhythmias and myocardial ischaemia, compared with dobutamine. Levosimendan produced haemodynamic responses that were unaffected by concomitant use of beta blockers.     

Myocardial depression associated with pneumococcal septic shock reversed by levosimendan

Levosimendan is a myocardial calcium sensitiser and potassium-ATP channel opener Levosimendan has been used in critically ill patients in various conditions to support myocardial function as an inotrope, lusitrope and vasodilator. We report the use of levosimendan in a patient with invasive streptococcal septic shock.     

No beneficial effects of levosimendan in acute porcine endotoxaemia

Background: Levosimendan has been proposed as an attractive alternative to adrenergic agents for the treatment of sepsis‐induced heart failure and haemodynamic derangements. Its use in this setting is, however, still not well investigated. The aim of this study was to test the hypothesis that levosimendan is able to attenuate endotoxin‐induced pulmonary hypertension and improve myocardial function in a porcine model. The secondary aims were to investigate its effect on renal and liver function, and the plasma cytokine response. Methods: Endotoxaemia was induced in 18 pigs, randomized to placebo and Levosimendan groups. All pigs were fluid resuscitated and Noradrenalin infusion was given according to a predefined protocol. Systemic haemodynamics and myocardial function were measured using pulmonary artery catheterization and transthoracic echocardiography. Renal and liver function tests and cytokine concentrations were measured in plasma. Results: Levosimendan did not attenuate endotoxin‐induced pulmonary hypertension and did not improve myocardial function. There were no differences in renal or liver function. Increases in arterial lactate and decreases in base excess were observed in the Levosimendan group, as well as significant increases in plasma interleukin (IL)‐6 and IL‐8. Conclusions: Contrary to our hypothesis, levosimendan given in conjunction with a protocolized vasopressor and fluid resuscitation did not improve cardiac, renal or liver function in this model of acute porcine endotoxaemia. Hyperlactataemia, acidosis and increases in plasma pro‐inflammatory cytokines were observed, the mechanisms and implications of which remain unclear.     

Levosimendan: calcium sensitizer and inodilator

Levosimendan is a unique therapeutic agent that decreases mortality in acute episodes of decompensated heart failure by increasing myocardial contractility without increasing oxygen consumption or ATP demands, decreasing preload, or decreasing afterload. The mechanism for each accomplishment is novel. The drug is a calcium sensitizer, which increases myocyte contractility by stabilizing troponin C rather than by increasing intracellular calcium. The drug may have implications in numerous other common and chronic medical ailments, even in overdoses of drugs that stun and depress the myocardium.     

Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of K(ATP) channels

We tested the hypothesis that levosimendan, a new positive inotropic drug that activates adenosine triphosphate-regulated potassium (K(ATP)) channels in vitro, decreases myocardial infarct size in vivo. Myocardial infarct size was measured after a 60-min left anterior descending coronary artery occlusion and 3 h of reperfusion in dogs receiving either IV vehicle (0.9% saline) or levosimendan (24 microg/kg bolus followed by an infusion of 0.4 microg x kg(-1) x min(-1)) in the presence or absence of glyburide (a K(ATP) channel antagonist) pretreatment (100 microg/kg). Levosimendan increased (P < 0.05) the maximal rate of increase of left ventricular pressure and decreased myocardial infarct size from 24%+/-2% (control experiments) to 11%+/-2% of the left ventricular area at risk for infarction. Glyburide did not alter the hemodynamic effects of levosimendan but blocked levosimendan-induced reductions of infarct size. Subendocardial collateral blood flow was similar among groups. However, levosimendan increased subepicardial and midmyocardial collateral perfusion in the absence, but not in the presence, of glyburide. Levosimendan exerts cardioprotective effects via activation of K(ATP) channels at a dose that simultaneously enhances myocardial contractility. IMPLICATIONS: Levosimendan may be advantageous in patients requiring inotropic support who are also at risk of myocardial ischemia. Activation of adenosine triphosphate-regulated potassium channels during infusion of levosimendan may produce cardioprotective effects while simultaneously enhancing ventricular contractile function.