BACKGROUND: The hemodynamic status of newborns with intracranial arteriovenous shunts (AVSs) may be extremely complex. Mini-invasive hemodynamic monitoring through innovative techniques such as Near-Infrared Spectroscopy (NIRS) and Pressure Recording Analytical Method (PRAM) may help in understanding hemodynamics in newborns with AVSs. Levosimendan is a calcium sensitizer and inodilator, and it is known to improve ventricular function, but its use in newborns is limited. In our cases, we evaluated the effect of levosimendan on hemodynamics through NIRS and PRAM.
METHODS: Herein, we report the cases of two neonates with intracranial arteriovenous shunts, in whom we used levosimendan to manage cardiac failure refractory to conventional treatment. Levosimendan was used at a dosage of 0.1 mcg/kg/min for 72 h. Combined use of NIRS and PRAM helped in real-time monitoring of hemodynamic effects; in particular, levosimendan determined significant improvement in myocardium contractility as well as a reduction of heart rate.
CONCLUSIONS: In two neonatal cases of AVSs, levosimendan led to an overall hemodynamic stabilization, documented by the combination of NIRS and PRAM. Our results suggest introducing levosimendan as a second-line treatment in cases of severe cardiac dysfunction due to AVSs without improvement using standard treatment strategies. Future prospective and larger studies are highly warranted.

Metal ions (Ag+, Cd2+, Eu3+, Sm3+) and protons can, through coordination and protonation, modulate in three specific ways the structural information contained in the pyrazine-based heterocyclic strand L (obtained from 2,5-bis(methylhydrazino)pyrazine and 2 equivalents of 2-pyridinecarboxaldehyde), thus generating two linear rod-like conformations and a bent one. This conformational diversity is associated with a structural one that consists of two diprotonated forms (H2L(PF6)2 and H2L(CF3SO3)2), a polymeric architecture [AgL]n(CF3SO3)n, two rack-like complexes ([Eu2H2L3(CF3SO3)6](PF6)2 and [Sm2H2L3(CF3SO3)6](PF6)2) and a grid-like structure ([Cd4L4](CF3SO3)8).

The oxidation activity of multicopper-oxidases overlaps with different substrates of laccases and bilirubin oxidases, thus in the present study an integrated approach of bioinformatics using homology modeling, docking, and experimental validation was used to confirm the type of multicopper-oxidase in Myrothecium verrucaria ITCC-8447. The result of peptide sequence of M. verrucaria ITCC-8447 enabled to predict the 3 D-structure of multicopper-oxidase. It was overlapped with the structure of laccase and root mean square deviation (RMSD) was 1.53 Å for 533 and, 171 residues. The low binding energy with azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (-5.64) as compared to bilirubin (-4.39) suggested that M. verrucaria ITCC-8447 have laccase-like activity. The experimental analysis confirmed high activity with laccase specific substrates, phenol (18.3 U/L), ampyrone (172.4 U/L) and, ampyrone phenol coupling (50 U/L) as compared to bilirubin oxidase substrate bilirubin (16.6 U/L). In addition, lowest binding energy with ABTS (-5.64), syringaldazine SYZ (-4.83), guaiacol GCL (-4.42), and 2,6-dimethoxyphenol DMP (-4.41) confirmed the presence of laccase. Further, complete remediation of two hazardous model pollutants i.e., phenol and resorcinol (1.5 mM) after 12 h of incubation and low binding energy of -4.32 and, -4.85 respectively confirmed its removal by laccase. The results confirmed the presence of laccase in M. verrucaria ITCC-8447 and its effective bioremediation potential.

Despite the progress in the management of cerebral arterial aneurysms, subarachnoid hemorrhage (SAH) remains the major cause of neurological disability. While SAH-related deaths usually occur as a result of brain impairment due to hemorrhage, permanent neurological deficits are caused by cerebral ischemia due to edema and spasm of cerebral arteries. Additionally, ~20%-30% of patients with SAH develop secondary cardiomyopathy; this phenomenon is known as neurogenic stress cardiomyopathy (NSC), which is associated with increased mortality and poor long-term prognosis. Levosimendan is a new inotropic drug that causes calcium sensitization of troponin C, thus increasing contraction force of myofilaments. The drug also causes opening of ATP-dependent potassium channels in vascular smooth muscles, which results in dilatation of veins and arteries, including cerebral arteries. To date, there have been several reports of levosimendan application in patients with SAH and neurogenic stress cardiomyopathy, and the effect of the drug on vasospasm has been previously advocated. This paper presents a case report of a 57-year-old patient with massive SAH, where levosimendan was used for reducing vasospasm.

Anthracycline-induced cardiomyopathy is a serious side effect that ranges from mild left ventricular systolic impairment to congestive heart failure and cardiogenic shock. Currently, there is no evidence indicating the effective use of levosimendan in these cases.
We aim to present a case of life-threatening doxorubicin-induced cardiomyopathy that was successfully managed with levosimendan.
A 48-year-old female with formerly normal heart function, who had been treated with doxorubicin-based regimens for dedifferentiated chondrosarcoma, presented with cardiomyopathy with low left ventricular ejection fraction eight months after the last infusion. As treatment with ramipril, carvedilol, and furosemide followed by dopamine and noradrenaline was not sufficient, levosimendan was administered. Left ventricular ejection fraction increased from 15% to 45% and her clinical condition improved.
Although anthracycline-induced cardiomyopathy may have a poor prognosis, levosimendan was shown to be effective in this patient. Therefore, levosimendan may represent a possible therapeutic option in such cases.

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We demonstrate the use of tethered bilayer lipid membranes (tBLMs) as an experimental platform for functional and structural studies of membrane associated proteins by electrochemical techniques. The reconstitution of the cholesterol-dependent cytolysin (CDC) pyolysin (PLO) from Trueperella pyogenes into tBLMs was followed in real-time by electrochemical impedance spectroscopy (EIS). Changes of the EIS parameters of the tBLMs upon exposure to PLO solutions were consistent with the dielectric barrier damage occurring through the formation of water-filled pores in membranes. Parallel experiments involving a mutant version of PLO, which is able to bind to the membranes but does not form oligomer pores, strengthen the reliability of this methodology, since no change in the electrochemical impedance was observed. Complementary atomic force microscopy (AFM) and neutron reflectometry (NR) measurements revealed structural details of the membrane bound PLO, consistent with the structural transformations of the membrane bound toxins found for other cholesterol dependent cytolysins. In this work, using the tBLMs platform we also observed a protective effect of the dynamin inhibitor Dynasore against pyolysin as well as pneumolysin. An effect of Dynasore in tBLMs, which was earlier observed in experiments with live cells, confirms the biological relevance of the tBLMs models, as well as demonstrates the potential of the electrochemical impedance spectroscopy to quantify membrane damage by the pore forming toxins. In conclusion, tBLMs are a reliable and complementary method to explore the activity of CDCs in eukaryotic cells and to develop strategies to limit the toxic effects of CDCs.

OBJECTIVE: To evaluate the cost-benefit of using levosimendan compared with dobutamine, in the perioperative treatment of patients undergoing cardiac surgery who require inotropic support.
METHODS: A two-part Markov model was designed to simulate health-state transitions of patients undergoing cardiac surgery, and estimate the short- and long-term health benefits of treatment. Hospital length of stay (LOS), mortality, medication, and adverse events were key clinical- and cost-inputs. Cost-benefits were evaluated in terms of costs and bed stays within the German healthcare system. Drug prices were calculated from the German Drug Directory (€/2014) and published literature, with a 3% annual discount rate applied. The base case analysis was for a 1-year time horizon.
RESULTS: The use of levosimendan vs dobutamine was associated with cost savings of €4787 per patient from the German hospital perspective due to reduced adverse events and shorter hospital LOS, leading to increased bed capacity and hospital revenue.
CONCLUSIONS: A pharmacoeconomic calculation for the specific situation of the German healthcare system that is based on international clinical trial carries a substantial risk of disregarding potentially relevant but unknown confounding factors (i.e., ICU-staffing, co-medications, standard-ICU care vs fast-tracking, etc.) that may either attenuate or increase the outcome pharmacoeconomic effects of a drug; however, since these conditions would also apply for patients treated with comparators, their net effects may not necessarily influence the conclusions.
CONCLUSIONS: The use of levosimendan in patients undergoing cardiac surgery who require inotropic support appears to be cost-saving. The results of the analysis provide a strong rationale to run local clinical studies with pharmacoeconomic end-points which would allow a much more precise computation of the benefits of levosimendan.

BACKGROUND: Levosimendan is a noncatecholamine inotrope that does not increase oxygen consumption, utilized for the treatment for acute heart failure with left ventricular (LV) systolic dysfunction. Its use in takotsubo cardiomyopathy (TTC), a disease that contraindicates the use of catecholamine inotropes, is not well known.
METHODS: We prospectively analyzed 13 consecutive patients with TTC, low ejection fraction (EF) (<35%), and additional Mayo Clinic risk factors who were treated with i.v. infusion of levosimendan. Clinical course of patients, electrocardiogram presentation, LV function, and adverse events at follow-up were recorded.
RESULTS: All patients showed an impaired LV function (LVEF at admission 28 ± 5%), which significantly improved at discharge (51 ± 8%, P < 0.001). Mean hospital stay was 10 ± 4 days. Troponin levels at admission were directly related to length of hospitalization (r = 0.6, P < 0.001). Male gender (relative risk (RR) 1.85, P < 0.05), physical stress (RR 1.90, P < 0.05), ST elevation at ECG (RR 1.87, P < 0.05), and absence of chest pain (RR 2.23, P < 0.01) were found to be the predictors of longer hospital stay. Only 15% of subjects had adverse events during hospital stay; two patients incurred noncardiovascular death at follow-up. Age was the only predictor of adverse event at follow-up (RR 2.13, P < 0.05).
CONCLUSIONS: The use of levosimendan may be safe and feasible in patients with TTC. Randomized studies are warranted to further confirm these preliminary results.

OBJECTIVE: The purpose of this study is to describe the effect of levosimendan (without loading dose) on hemodynamics, inotropes/vasopressors, and mortality in acute heart failure (AHF).
METHODS: Patients who received levosimendan for AHF were analyzed. Levosimendan dose, hemodynamic data, inotrope/vasopressor requirements, and fluid balance before commencement, at conclusion of, and 24 hours after levosimendan were collected. Mortality is also reported.
RESULTS: Eighty-seven patients were analyzed. The mean levosimendan dose (without loading) was 0.096 μg/kg per minute (±0.014), and mean duration, 26 (±7.2) hours. There was no change in heart rate (start, post, and 24 hours post) (92 [±19], 92 [±26], and 92 [±15]) or mean arterial pressure (69 [±10], 72 [±8], and 72 [±10] mm Hg, respectively). There was a significant reduction in median dobutamine from 7.27 to 0 μg/kg per minute and noradrenaline from 0.20 to 0.1 μg/kg per minute before and 24 hours after. There was a significant increase in both mean cardiac index from 2.38 ± 0.0.72 to 2.98 ± 0.0.77 L/min per square meter and in markers of perfusion: base excess from -2.77 to 0.39 mmol/L, and lactate from 2.1 to 1.4 mmol/L before and 24 hours after infusion. Survival was 53%.
CONCLUSIONS: Levosimendan, without a loading dose, improved cardiac index and perfusion while allowing a reduction in inotropic/vasopressor requirements in patients with AHF.