Hemodynamic Effects of Calcium-Sensitizing Agents

Végh, Ágnes; Papp, Julius Gy.; Udvary, Éva; Kaszala, Károly

doi:10.1097/00005344-199506261-00004

Cited by 27 publications

(13 citation statements)

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“…On the basis of animal studies [10] , we would have expected levosimendan to have more potent coronary vasodilating activity. A tendency towards an increase in coronary blood flow and a statistically significant decrease in coronary vascular resistance after the higher dose of levosimendan was observed.…”

Section: Findings and Implicationsmentioning

confidence: 99%

“…In addition, levosimendan has selective phosphodiesterase III inhibitory properties, but no increase of cyclic adenosine monophosphate at therapeutic concentrations contributes to the inotropic effect of levosimendan [8,9] . Végh et al [10] have shown in anaesthetized dogs after experimental acute heart failure induced by ligation of the left anterior descending artery and critical constriction of the left circumflex artery that levosimendan increased coronary blood flow and myocardial contractility depressed by ischaemia. We have previously demonstrated that levosimendan has combined inotropic and systemic vasodilatory effects in both healthy volunteers and patients with left ventricular dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting

Lilleberg

Nieminen²,

Akkila³

et al. 1998

European Heart Journal

227

118

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AimsThe aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocardial substrate utilization of a new calcium sensitizer, levosimendan, after coronary artery bypass grafting. Methods and ResultsTwenty-three low-risk patients were included in this randomized and double-blind study. They received placebo (n=8), 8 (n=8) or 24 (n=7) g . kg 1 of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats . min 1 after the higher dose (P<0·05). Cardiac output increased by 0·7 and 1·6 l . min 1 (P<0·05 for both) after 8 and 24 g . kg 1 of levosimendan, respectively. Systemic and pulmonary vascular resistance decreased significantly after both doses. Coronary sinus blood flow increased by 28 and 42 ml/(P=0·054 for the combined effect) after the lower and higher dose, respectively. Myocardial oxygen consumption or substrate extractions did not change statistically significantly.Conclusion Despite improved cardiac performance, levosimendan did not increase myocardial oxygen consumption or change myocardial substrate utilization. Thus levosimendan has the potential to treat low cardiac output states after cardiopulmonary bypass surgery.

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Section: Findings and Implicationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting

Lilleberg

Nieminen²,

Akkila³

et al. 1998

European Heart Journal

227

118

View full text Add to dashboard Cite

show abstract

“…Levosimendan (0.3 mol/kg intravenously) reduced coronary vascular resistance and increased coronary blood flow by about 30% in anesthetized dogs with acute heart failure secondary to coronary artery ligation [13]. Improved blood flow was observed even through the experimentally stenosed artery.…”

Section: Preclinical Pharmacology Of Levosimendanmentioning

confidence: 97%

Levosimendan: A promising agent for the treatment of hospitalized patients with decompensated heart failure

Lehtonen

2000

Curr Cardiol Rep

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Levosimendan is a new inodilator, whose mechanism of action includes calcium sensitization of contractile proteins and the opening of ATP-dependent potassium channels. The combination of positive inotropy with anti-ischemic effects of K-channel opening offers many potential benefits in comparison to currently available intravenous inotropes, that are more or less contraindicated in patients with ongoing myocardial ischemia. Levosimendan has been extensively studied in various animal models of heart failure, in which the drug has increased contractility without adverse effects on diastolic function. These results have been repeated in patients with heart failure, by whom levosimendan dose-dependently increases cardiac output and reduces pulmonary capillary wedge pressure. On higher doses, the drug can induce tachycardia and hypotension. In clinical trials, drug-induced ventricular arrhythmia have been rare. Recently, trials in patients with decompensated heart failure have suggested that short-term intravenous treatment with levosimendan might improve the survival of these critical patients. These results highlight the importance of adequate treatment of the acute heart failure patients for their long-term outcome.

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“…Levosimendan (0.3 µmol/kg) reduced coronary vascular resistance and increased coronary blood flow by approximately 30% in anesthetized dogs with acute heart failure secondary to coronary artery ligation [14]. Improved blood flow was observed even through the constricted artery.…”

Section: Pharmacology Of Levosimendanmentioning

confidence: 98%

Levosimendan: A calcium-sensitizing agent for the treatment of patients with decompensated heart failure

Lehtonen

2004

Curr Heart Fail Rep

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Levosimendan is a new inodilator. Its mechanism of action includes calcium sensitization of contractile proteins and the opening of adenosine triphosphate-dependent K channels. The combination of positive inotropy with anti-ischemic effects of K-channel opening offers potential benefits in comparison with currently available intravenous inotropes, which are contraindicated in patients with ongoing myocardial ischemia. Levosimendan has been extensively studied in various animal models of heart failure, in which the drug has increased contractility without adverse effects on diastolic function. These results have been repeated in patients with heart failure, in whom levosimendan dose-dependently increases cardiac output and reduces pulmonary capillary wedge pressure. The active metabolite of levosimendan (OR-1896) significantly prolongs the duration of the hemodynamic effects of the therapeutic 24-hour levosimendan infusion. Levosimendan has been studied in two major trials with decompensated patients (LIDO and RUSSLAN), in which it showed outcome benefits in comparison with dobutamine and placebo, respectively. A third comparative study (CASINO) recently suggested mortality benefits with levosimendan over placebo and dobutamine. Currently, two large prospective trials (SURVIVE and REVIVE) in patients who are hospitalized because of worsening heart failure are underway. These trials will conclusively prove whether levosimendan should be added to the standard treatment in patients who are hospitalized because of cardiac decompensation.

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Hemodynamic Effects of Calcium-Sensitizing Agents

Cited by 27 publications

References 0 publications

Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting

Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting

Levosimendan: A promising agent for the treatment of hospitalized patients with decompensated heart failure

Levosimendan: A calcium-sensitizing agent for the treatment of patients with decompensated heart failure

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