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41.
42.
Akar F Manavbasi Y Parlar AI Ulus AT Katircioglu SF 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2007,21(5):331-338
Purpose The mechanism of the vasorelaxation to levosimendan varies depending on the vascular bed and species studied. Here, we examined
the vasorelaxation to levosimendan as well as its modification by various potassium channel antagonists in human internal
mammary artery (IMA) obtained from male and female patients.
Methods IMA grafts were supplied from 27 male and 19 age-matched female patients undergoing coronary bypass operation. The contraction
to noradrenaline and relaxation to levosimendan were studied in IMA rings obtained from both gender. The relaxations to levosimendan
were also assessed in the presence of glibenclamide (10 μM), an adenosine triphosphate-sensitive potassium channel (KATP) blocker, or charybdotoxin (100 nM), a calcium-activated potassium channel (KCa) blocker, or 4-aminopyridine(1 mM), a voltage-sensitive potassium channel (Kv) inhibitor.
Results Concentration–response curves to noradrenaline were not different in IMA rings from either gender. Pretreatment with levosimendan
(3 × 10−7 M) slightly modified the contractions to noradrenaline in both gender. Levosimendan (10−9–10−5 M) produced concentration-dependent relaxation in IMA rings, contracted by noradrenaline (5 × 10−6 M), from males and females. The vasodilatory effects of levosimendan were more pronounced in the arteries from males (83%)
than females (69%), in term of the maximal relaxation (E
max). Charybdotoxin and glibenclamide significantly inhibited the relaxation to levosimendan in the arteries from males but not
in those of females.
Conclusions The vasodilating efficacy of levosimendan and its relaxation mechanism differs between the arteries from males and females,
which may have clinical consequences in the treatment of heart failure. 相似文献
43.
Koudouna E Xanthos T Bassiakou E Goulas S Lelovas P Papadimitriou D Tsirikos N Papadimitriou L 《Acta anaesthesiologica Scandinavica》2007,51(8):1123-1129
BACKGROUND: Cardiac arrest remains the leading cause of death in Western societies. Advanced Life Support guidelines propose epinephrine (adrenaline) for its treatment. The aim of this study was to assess whether a calcium sensitizer agent, such as levosimendan, administered in combination with epinephrine during cardiopulmonary resuscitation, would improve the initial resuscitation success. METHODS: Ventricular fibrillation was induced in 20 Landrace/Large-White piglets, and left untreated for 8 min. Resuscitation was then attempted with precordial compressions, mechanical ventilation and electrical defibrillation. The animals were randomized into two groups (10 animals each): animals in Group A received saline as placebo (10 ml dilution, bolus) + epinephrine (0.02 mg/kg), and animals in Group B received levosimendan (0.012 mg/kg/10 ml dilution, bolus) + epinephrine (0.02 mg/kg) during cardiopulmonary resuscitation. Electrical defibrillation was attempted after 10 min of ventricular fibrillation. RESULTS: Four animals in Group A showed restoration of spontaneous circulation and 10 in Group B (P = 0.011). The coronary perfusion pressure, saturation of peripheral oxygenation and brain regional oxygen saturation were significantly higher during cardiopulmonary resuscitation in Group B. CONCLUSIONS: A calcium sensitizer agent, when administered during cardiopulmonary resuscitation, significantly improves initial resuscitation success and increases coronary perfusion pressure during cardiopulmonary resuscitation. 相似文献
44.
Ozdem SS Yalcin O Meiselman HJ Baskurt OK Usta C 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2006,20(2):123-127
Summary We investigated both the effect of levosimendan and the role of various potassium channels in KCl-precontracted rat small mesenteric arteries. Levosimendan (10−6−10−3 M) or cromakalim (CRO, 10−7−10−4 M) produced concentration-dependent relaxation responses in small mesenteric arteries precontracted by 30 mM KCl. The relaxant
responses to levosimendan in KCl-precontracted arteries did not differ significantly between endothelium-intact and endothelium-denuded preparations.
Incubation of rat small mesenteric arterial segments with ATP-dependent potassium channel (KATP) blocker glibenclamide (GLI,
10−6 M) for 30 min significantly inhibited the relaxant responses to both levosimendan and CRO. Neither the Ca2+-activated potassium channel (KCa) blocker iberiotoxin (10−7 M) nor the voltage-dependent potassium channel (KV) blocker 4-aminopyridine (5 mM) incubation for 30 min caused significant
alterations in relaxant responses to levosimendan in KCl-precontracted small mesenteric arteries. These findings suggested that levosimendan-induced relaxation responses in isolated rat small mesenteric arteries were neither depended on endothelium nor inhibited
by the blockers of KV or KCa but, they rather seem to depend on the activation of KATP. 相似文献
45.
46.
左西孟旦是一种新型正性肌力药--钙增敏剂,可通过钙敏作用增强心肌收缩力,激活K+通道使血管扩张,且并不增加心肌氧耗和心率,因而具有改善心功能和心肌保护等作用.可应用于治疗急性失代偿心力衰竭、心肌缺血后心脏收缩力异常、心肌顿抑以及用于心脏手术期间循环的调控等方面. 相似文献
47.
48.
Cleland JG Takala A Apajasalo M Zethraeus N Kobelt G 《European journal of heart failure》2003,5(1):101-108
BACKGROUND: Levosimendan, a novel calcium sensitiser, improves cardiac performance and symptoms without increasing oxygen consumption, and decreases the mortality of patients with low-output heart failure. AIMS: To estimate the cost-effectiveness of intravenous treatment with levosimendan compared with dobutamine in patients with severe low-output heart failure. METHODS: This economic evaluation was based on a European clinical trial (LIDO), in which 203 patients with severe heart failure randomly received a 24 h infusion with either levosimendan or dobutamine. Survival and resource utilisation data were collected for 6 months; survival was extrapolated assuming a mean additional lifetime of 3 years based on data from the Cooperative North Scandinavian Enalapril Survival Study trial. Costs were based on study drug usage and hospitalisation in the 6-month follow-up. A sensitivity analysis on dosage of drug and duration of survival was performed. RESULTS: The mean survival over 6 months was 157+/-52 days in the levosimendan group and 139+/-64 days in the dobutamine group (P<0.01). When extrapolated up to 3 years, the gain in life expectancy was estimated at 0.35 years (discounted at 3%). Levosimendan increased the mean cost per patient by 1108, which was entirely due to the cost of the study drug. The incremental cost per life-year saved (LYS) was 3205 at the European level; in the individual countries the cost per LYS ranged between 3091 and 3331. The result was robust in the sensitivity analysis. CONCLUSIONS: Although the patients in the levosimendan group were alive for more days and thus at risk of hospitalisation for longer, there was no increase in hospitalisation or hospitalisation costs with levosimendan treatment. The cost per LYS using levosimendan compares favourably with other cost-effectiveness analyses in cardiology. 相似文献
49.
Jonsson EN Antila S McFadyen L Lehtonen L Karlsson MO 《British journal of clinical pharmacology》2003,55(6):544-551
AIMS: The aim of this study was to characterize the population pharmacokinetics of levosimendan in patients with heart failure (NYHA grades III and IV) and its relationship to demographic factors, disease severity and concomitant use of digoxin and beta-blocking agents. METHODS: Data from two efficacy studies with levosimendan administered by intravenous infusion were combined (190 patients in total). The data were analysed using a nonlinear mixed-effects modelling approach as implemented in the NONMEM program. The model development was done in three sequential steps. First the best structural model was determined (e.g. a one-, two- or three-compartment pharmacokinetic model). This was followed by the identification and incorporation of important covariates into the model. Lastly the stochastic part of the model was refined. RESULTS: A two-compartment model best described levosimendan pharmacokinetics. Clearance and the central volume of distribution were found to increase linearly with bodyweight. No other covariates, including concomitant use of digoxin and beta-blocking agents, influenced the pharmacokinetics. In the final model, a 76-kg patient was estimated to have a clearance +/- s.e. of 13.3 +/- 0.4 l h-1 and a central volume of distribution of 16.8 +/- 0.79 l. The interindividual variability was estimated to be 39% and 60% for clearance and central volume of distribution, respectively. Weight changed clearance by 1.5% [95% confidence interval (CI) 0.9%, 2.1%] and the central volume of distribution by 0.9% (95% CI 0.5%, 1.3%) per kg. CONCLUSIONS: The population pharmacokinetics parameters of levosimendan in this patient group were comparable to those obtained by traditional methods in healthy volunteers and patients with mild heart failure. Bodyweight influenced the clearance and the central volume of distribution, which in practice is accounted for by weight adjusting doses. None of the other covariates, including digoxin and beta-blocking agents, significantly influenced the pharmacokinetics of levosimendan. 相似文献
50.
Brixius K Hoyer HK Schwinger RH 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2005,19(6):423-428
Summary Because the number of transplants is still fewer than the number of patients waiting for a donor organ, new concepts of therapy
are needed that allow patients to bridge the time gap until heart transplantation or even to improve symptoms while on treatment.
Ca2+-sensitisers are agents that directly influence myofilaments and/or the cross-bridge-cycle. Depending on the molecular mechanisms
underlying their action, Ca2+-sensitisers have been divided into three classes. While, a number of Ca2+-sensitising drugs have been described, currently only the Ca2+-sensitisers pimobendan and levosimendan are in clinical use. This review provides a survey on the molecular mechanisms and
the therapeutic effectiveness of Ca2+-sensitisers for the treatment of human heart failure. 相似文献