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At least 73 records · Page 4Linked to original sources
PubMed2006

Effect of levosimendan on ventricular arrhythmias and prognostic autonomic indexes in patients with decompensated advanced heart failure secondary to ischemic or dilated cardiomyopathy.

Positive inotropes used for the treatment of heart failure have been arrhythmogenic. Levosimendan is a novel calcium sensitizer with vasodilating properties and a complex mechanism of action. Its effect on ventricular arrhythmias and 24-hour Holter electrocardiographically derived prognostic autonomic nervous system-related markers, because it occurs in parallel with changes in cardiac function and neurohormonal response, has not been systematically assessed. Forty-five patients (mean age 65 +/- 1.3 years) with heart failure refractory to conventional therapy and a mean ejection fraction of 23 +/- 1.2%, randomized to levosimendan or placebo, were studied. After Holter electrocardiographic recording, 1 drug was infused for 24 hours (levosimendan at a dose of 0.1 mug/kg/min). During this period, another Holter recording was performed to assess changes in ventricular arrhythmogenesis, 24-hour heart rate variability indexes, QTc, QT variability, and QT/RR slope. Clinical evaluation, echocardiography, and B-type natriuretic peptide measurements were performed at baseline and after treatment. After levosimendan, clinical and echocardiographic improvement was observed, associated with beneficial neurohormonal modulation (mean B-type natriuretic peptide level after levosimendan 668 +/- 108 vs 1,009 +/- 122 pg/ml at baseline, p <0.05). Episodes of nonsustained ventricular tachycardia increased with levosimendan (21.9 +/- 9.6 vs 3.0 +/- 1.2, p <0.05). Levosimendan and placebo exerted a neutral effect on all autonomic markers assessed. In conclusion, levosimendan at low doses increases nonsustained ventricular arrhythmias, without affecting Holter-derived, prognostically significant autonomic markers. At the same time, it is associated with improvements in cardiac function and neurohormonal response. These findings may have important clinical and prognostic implications.

Aged↗
PubMed2006

Levosimendan in cardiac surgery: current best available evidence.

Recent upsurge in referral of patients with high perioperative risk or compromised left ventricular function for cardiac surgery has lead to an increasing use of pharmacologic support in the form of vasodilator and inotropic therapy to achieve improvement of tissue perfusion in the perioperative period or to support weaning from cardiopulmonary bypass. Traditionally, perioperatively used inotropic agents, epinephrine, dobutamine, and milrinone, are limited by significant increases in myocardial oxygen consumption, proarrhythmia, or neurohormonal activation. Levosimendan, a new inodilator for the treatment of decompensated heart failure, has also shown promise in elective therapy of cardiac surgical patients with high perioperative risk or compromised left ventricular function, as well as in rescue therapy of patients with difficult weaning from cardiopulmonary bypass. This review article briefly discusses the pharmacology of levosimendan and evaluates current best available evidence to assess the safety and efficacy of levosimendan usage in cardiac surgery.

Adult↗
PubMed2006

Potassium channel-related relaxation by levosimendan in the human internal mammary artery.

BACKGROUND: Levosimendan is a potent inotropic and vasodilator drug used in the treatment of decompensated heart failure. There is no study on in vitro effects of levosimendan in human isolated arteries. METHODS: We investigated the effect of levosimendan on contractile tone of human isolated internal mammary artery (IMA). The responses in IMA were recorded isometrically by a force-displacement transducer in isolated organ baths. Levosimendan was added to organ baths either at rest or after precontraction with phenylephrine (1 micromol/L). Levosimendan-induced relaxations were tested in the presence of cyclooxygenase inhibitor indomethacin (10 micromol/L), nitric oxide synthase inhibitor N122-nitro-L-arginine methyl ester (100 micromol/L), large-conductance calcium-activated potassium-channel inhibitor tetraethylammonium (1 mmol/L), adenosine triphosphate-sensitive potassium-channel inhibitor glibenclamide (10 micromol/L), and voltage-sensitive potassium-channel inhibitor 4-aminopyridine (1 mmol/L). RESULTS: Levosimendan (10 nmol/L to 3 micromol/L) produced potent relaxation in human IMA (maximal effect, 75.3% +/- 4.9% of phenylephrine maximum contraction, 6.8 +/- 0.1, n = 15; -log10 of 50% effective concentration). Vehicle had no significant relaxant effect. The relaxation to levosimendan is not affected by either potassium-channel inhibitors (tetraethylammonium and 4-aminopyridine) or cyclooxygenase and nitric oxide synthase inhibitors. Glibenclamide (10 micromol/L) inhibited levosimendan-induced relaxation significantly (p < 0.01). CONCLUSIONS: Levosimendan effectively and directly decreases the tone of IMA. The mechanism of levosimendan-induced relaxation in IMA appears in part to be adenosine triphosphate-sensitive potassium-channel opening action. Levosimendan may be a cardiovascular protective agent by its relaxing action on the major arterial graft, IMA.

Aged↗
PubMed2006

Levosimendan reversing low output syndrome after heart transplantation.

After heart transplantation primary graft failure is a major cause of early mortality. Treatment options include inotropes and mechanical assist devices. Developing better methods would impact on patients' short- and long-term survival. We present a case of primary graft failure manifested as cardiogenic shock unresponsive to catecholamines and a phosphodiesterase inhibitor. Reversal of low output syndrome was achieved with a new type of inotropic agent, levosimendan, leading to the later complete recovery.

Cardiotonic Agents↗
PubMed2006

Intracoronary infusion of levosimendan to treat postpericardiotomy heart failure.

Systemic hypotension limits the intravenous use of levosimendan, particularly in coronary disease. Published reports show that the intracoronary administration of levosimendan in animal models causes an increase of coronary blood flow without systemic hypotension. In this case report, the intracoronary administration of levosimendan bolus in a 74-year-old man with postpericardiotomy heart failure elicited beneficial cardiac effects, increasing both systolic and diastolic functions and blood flow in all of the grafts. No changes of heart rate and systemic arterial blood pressure were observed.

Aged↗
PubMed2004

Potassium-specific effects of levosimendan on heart mitochondria.

In this study, we evaluated levosimendan, a new drug developed for the treatment of acute and decompensated heart failure, as a potential activator of ATP-sensitive potassium flux to the matrix of cardiac mitochondria. We estimated the KATP channel openers-induced increase in mitochondrial inner membrane permeability for potassium by registering changes in membrane potential of heart mitochondria, oxidizing endogenous substrates. We compared the effect of levosimendan with the effects of the known KATP channel openers diazoxide and pinacidil. Levosimendan (1 microM) accelerated potassium-specific DeltaPsi decrease by 0.15%/s, whereas 50 microM diazoxide by 0.10%/s, and 50 microM pinacidil by 0.08%/s, respectively. These results were confirmed by swelling experiments of non-respiring mitochondria in potassium nitrate medium. We found that levosimendan with an EC50 of 0.83 +/- 0.24 microM activates potassium flux to the mitochondrial matrix. This effect is discussed as a possible explanation of the anti-ischemic action of levosimendan.

Animals↗
PubMed2006

Effects of levosimendan on left ventricular diastolic function after primary angioplasty for acute anterior myocardial infarction: a Doppler echocardiographic study.

BACKGROUND: Levosimendan is a new Ca-sensitizing drug with combined positive inotropic and vasodilatory effects that offers new therapeutic possibilities in patients with severe heart failure. Compared with other inotropic agents, animal studies demonstrated that levosimendan does not impair left ventricular diastolic function. OBJECTIVE: We sought to evaluate the effects of levosimendan on left ventricular diastolic function, using conventional transmitral Doppler and Doppler tissue imaging parameters, in patients with anterior acute myocardial infarction undergoing primary angioplasty. METHODS: After a successful primary angioplasty, we randomized 52 consecutive patients with anterior acute myocardial infarction to levosimendan or placebo infusion and analyzed the diastolic function using conventional transmitral Doppler flow and Doppler tissue imaging at mitral annulus. RESULTS: At 24 hours after the index intervention, patients treated with levosimendan (n = 26) showed a significant reduction of the isovolumetric relaxation time (114.6 +/- 15.1-69.2 +/- 5.6 milliseconds; P = .001) and the ratio between the early diastolic flow and early tissue velocity (E/E') (21.4 +/- 10.7-12.8 +/- 7.3; P = .04), and a significant increase of the ratio between the early and late diastolic flow (E/A) (0.86 +/- 0.33-1.52 +/- 0.88; P = .03) and E' (6.4-7.9 cm/s; P = .001). On the other hand, only a significant increase in E/A ratio (0.97 +/- 0.32-1.64 +/- 0.51; P = .002) was observed in the placebo group (n = 26). CONCLUSIONS: Levosimendan, after primary angioplasty in patients with anterior acute myocardial infarction, appears to improve the Doppler echocardiographic parameters of left ventricular diastolic function.

Angioplasty, Balloon↗
PubMed2004

Treatment of acute heart failure in an infant after cardiac surgery using levosimendan.

An infant, 2 months old, underwent cardiac surgery because of congenital heart defects and pulmonary hypertension. Surgery was performed in hypothermia and cardiac standstill. On the second day after surgery the infant had to be resuscitated due to a combination of acute left-ventricular failure, pulmonary vascular hypertension and a slight right-to-left-shunt. A breakthrough in the treatment was achieved by using levosimendan to improve left-ventricular function and to decrease vascular resistance.

Cardiotonic Agents↗
PubMed2006

The role of potassium channels in the vasodilatory effect of levosimendan in human internal thoracic arteries.

OBJECTIVE: We investigated the role of potassium channels in vasodilatory effect of levosimendan in human internal thoracic arteries. METHODS: Samples of redundant internal thoracic arteries obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. RESULTS: Levosimendan (10(-8)-10(-5) M) or cromakalim (10(-8)-10(-5) M) produced concentration-dependent relaxation responses in human internal thoracic arteries precontracted by 10(-6) M phenylephrine. The relaxant responses to levosimendan did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human internal thoracic artery rings with adenosine 3',5'-triphosphate (ATP)-dependent potassium channel blocker glibenclamide (10(-6) M) for 30 min significantly inhibited the relaxant responses to both levosimendan and cromakalim. The Ca2+-activated potassium channel blocker iberiotoxin (10(-7) M) also caused a significant but smaller inhibition on relaxant responses to levosimendan. Incubation of the rings with the voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) for 10 min did not cause significant alterations in relaxant responses to levosimendan. CONCLUSIONS: The findings of this study suggested that levosimendan-induced relaxation responses in human internal thoracic arteries were depended on the activation of ATP-dependent and Ca2+-activated potassium channels.

Aged↗
PubMed2005

The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine.

AIM: To investigate the effect of a new inotropic drug, levosimendan compared with dobutamine on levels of brain natriuretic peptide (BNP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and malondialdehyde (MDA) in patients with severe decompensated heart failure. METHODS AND RESULTS: Twenty-nine consecutive patients (22 males and 7 females), mean age 70.5+/-9.9 years, with decompensated heart failure on standard medical therapy, were randomised to receive either a 24 h infusion of levosimendan (n=15) or dobutamine (n=14). Blood samples were drawn at baseline, 48 h and 5 days post infusion. Levosimendan produced a significant reduction in BNP compared to baseline, at both 48 h (744.1+/-100 vs 1136.3+/-93.7 pg/ml, p=0.04) and 5 days (446+/-119.3 vs 1136.3+/-93.7 pg/ml, p=0.03), while IL-6 values decreased after 5 days (4.8+/-1.3 vs 8.6+/-1.5 pg/ml, p=0.01). MDA levels were significantly lower 5 days after levosimendan compared to baseline (2.3+/-0.2 vs 3+/-0.3 microM, p=0.01). TNF-alpha levels did not differ between the groups. The comparison of percentage alteration compared to baseline showed that BNP (-44.5+/-7.6% vs 4.8+/-18.7%, p=0.025), MDA (-21.8+/-5.1% vs 14.9+/-8.5%, p=0.001) and IL-6 (-38.8+/-12.5% vs 70.2+/-24%, p=0.001) levels were significantly lower in the levosimendan group 5 days after treatment compared to the dobutamine group. CONCLUSIONS: Treatment with levosimendan in advanced decompensated heart failure exerts a beneficial hemodynamic, anti-inflammatory and antioxidant effect. These findings may give an insight into the favourable impact on mortality that levosimendan appears to have in published multicenter trials.

Adrenergic beta-Agonists↗
PubMed2005

Short-term effects of levosimendan and prostaglandin E1 on hemodynamic parameters and B-type natriuretic peptide levels in patients with decompensated chronic heart failure.

BACKGROUND: Both levosimendan and prostaglandin E1 (PGE1) have beneficial effects on hemodynamic parameters and outcome compared to dobutamine in decompensated chronic heart failure (CHF). AIMS: We compared short-term effects of levosimendan versus PGE1 on hemodynamic parameters and B-type natriuretic peptide levels (BNP) in patients with decompensated CHF. METHODS AND RESULTS: 73 patients (cardiac index < 2.5 L/min/m2, pulmonary capillary wedge pressure (PCP) >15 mmHg) with decompensated CHF were randomised to treatment with either a 24 h-infusion of levosimendan (n=38) or a chronic infusion of PGE1 (n = 35). Hemodynamic parameters and BNP were measured at baseline, 24 and 48 h, BNP levels were also measured after 1 week. Baseline characteristics including concomitant medication were similar in both groups. Levosimendan and PGE1 increased cardiac output (CO) after 24 and 48 h. Levosimendan increased CO twice as much as PGE1 (24 h: Levosimendan +1.1 +/- 0.1 L/min, PGE1 +0.6 +/- 0.1 L/min, p < 0.001). Both drugs produced a comparable reduction in PCP and pulmonary artery pressure after 24 and 48 h. Levosimendan decreased BNP by 28% after 24 h and 22% after 48 h, but effects disappeared after 1 week. In contrast, PGE1 decreased BNP by 15% after 48 h (no change at 24 h), but a decrease of 20% was sustained at 1 week. CONCLUSIONS: The differential beneficial effects of levosimendan (greater increase in CO) and PGE1 (sustained decrease in BNP) may have a potential impact on clinical outcome.

Adolescent↗
PubMed2006

Cardiogenic shock after primary percutaneous coronary intervention: Effects of levosimendan compared with dobutamine on haemodynamics.

BACKGROUND: Levosimendan is a new calcium sensitizer with positive inotropic properties. Cardiac power output (CPO) has been shown to be instrumental in the diagnosis of cardiogenic shock (CS) and is an important determinant of outcomes. AIMS: To evaluate the haemodynamic effects of levosimendan compared to dobutamine in acute myocardial infarction (AMI) patients revascularised by primary percutaneous coronary intervention (PCI), who developed CS. METHODS AND RESULTS: Twenty two consecutive AMI patients revascularised by PCI, who developed CS, were randomly assigned to levosimendan (24 microg kg(-1) bolus plus 24-h continuous infusion 0,1 microg kg(-1) min(-1)) or dobutamine (initial dose 5 microg kg(-1) min(-1), with a maximum dose adjustment in order to reach the desired haemodynamic effect). Evaluations were performed from baseline to 30 h. The primary end-point was an increase > or =30% in CPO, after 24 h of therapy. The baseline clinical and haemodynamic characteristics were similar in both groups. Levosimendan had a consistently better effect on CPO than dobutamine, while the decrease in PCWP was similar. CONCLUSION: The primary objective of our study was achieved better by the end of the 24 h infusion of levosimendan than by dobutamine.

Aged↗
PubMed2006

Long-term effects of levosimendan infusion on inflammatory processes and sFas in patients with severe heart failure.

BACKGROUND: The calcium sensitizer levosimendan improves myocardial contractility in patients with heart failure, although its effects on inflammation and apoptosis are unknown. AIM: To examine the effects of levosimendan on markers of inflammation and apoptosis, over a period of 30 d following a 24 h infusion, in patients with heart failure. METHODS: Thirty four patients with severe heart failure were randomised to receive a 24 h infusion of levosimendan or placebo, in a double-blind trial. Haemodynamic evaluation and blood sampling were performed at baseline, 24 h, 30 h, 48 h, 7 d and 30 d after the end of the infusion. RESULTS: Seven patients (1 levosimendan, 6 placebo), were excluded during follow-up. In the remaining 27 patients, levosimendan decreased serum IL-6 and sFAS, 24 h after the infusion (p<0.01 and p<0.05 vs baseline), an effect sustained for 7-30 d. Serum TNF-alpha and sTNF-R1 were decreased between 48 h (p<0.01 vs baseline for both) and 7 d (p<0.05 vs baseline for sTNF-R1) after infusion. Serum sTNF-R2 was decreased at 24 h (p<0.05 vs baseline) and remained lower than baseline for at least 7 d (p<0.05). CONCLUSIONS: These findings indicate that levosimendan decreases the expression of proinflammatory cytokines, TNF-alpha receptors and sFAS, immediately after infusion, an effect which persists for 7-30 d.

Aged↗
PubMed2006

Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure.

AIMS: To determine the duration of haemodynamic and neurohormonal action of a 24-h infusion of levosimendan in heart failure. METHODS AND RESULTS: This was a double-blind, parallel group study in patients with New York Heart Association class II to IV heart failure. Twenty-two patients, with left ventricular ejection fraction <35% and pulmonary capillary wedge pressure (PCWP) above 12 mmHg, were randomised to receive either levosimendan (12 microg/kg followed by a continuous infusion of 0.1-0.2 microg/min) or placebo. Invasively measured cardiac output (CO) increased from 4.3 l/min to 5.4 l/min in the levosimendan group at 6 h. PCWP decreased from 20 mmHg to 15 mmHg in response to levosimendan. Echocardiographically measured maximal effect on PCWP occurred after 6 h, whereas CO reached its highest value at 24 h. The estimated duration of the decrease in PCWP was 7-9 days, and in CO was 12-13 days. Plasma NT-proANP and NT-proBNP levels reached their lowest values at days 3 and 2, and the treatment effect was estimated to last 16 and 12 days, respectively. The long-acting haemodynamic responses reflect levels of the active metabolites OR-1896 and OR-1855, maximal metabolite levels occurred at day 3. CONCLUSIONS: Levosimendan infusion achieved a rapid improvement in haemodynamic parameters in patients with congestive heart failure with maximal effects occurring 1-3 days after starting the infusion, effects were sustained for up to at least a week.

Atrial Natriuretic Factor↗