Levosimendan
Also known as: Simdax
Levosimendan is a calcium sensitizer and inodilator that enhances cardiac contractility without increasing myocardial oxygen consumption. This compound opens ATP-sensitive potassium channels and inhibits phosphodiesterase III, making it valuable for heart failure research.
Levosimendan is a 280.28 g/mol research peptide. Levosimendan is a calcium sensitizer and inodilator that enhances cardiac contractility without increasing myocardial oxygen consumption. This compound opens ATP-sensitive potassium channels and inhibits phosphodiesterase III, making it valuable for heart failure research.
Also called: Simdax
280.28 g/mol
Molecular Weight
Daltons
4
Strong Evidence
benefits
4
Studies Cited
peer-reviewed
0.05-0.2
Typical Dose
mcg/kg/min
Overview
Levosimendan represents a unique class of cardiovascular agents that combines positive inotropic effects with vasodilation through dual mechanisms. The compound binds to cardiac troponin C in a calcium-dependent manner, stabilizing the calcium-induced conformational change that exposes myosin-binding sites on actin filaments. This mechanism increases contractile force without raising intracellular calcium levels, distinguishing it from traditional inotropes. Additionally, levosimendan activates ATP-sensitive potassium channels in vascular smooth muscle and cardiomyocytes, producing vasodilation and potential cardioprotective effects. Its active metabolite OR-1896 provides sustained hemodynamic benefits lasting days beyond the parent compound's elimination. Research applications focus on acute heart failure, cardiogenic shock, and perioperative cardiac protection studies.
Key Takeaways: Levosimendan
- Strongest evidence supports Levosimendan for enhanced cardiac contractility and vasodilation and preload reduction
- Research doses typically range from 0.05 to 0.2 mcg/kg/min via iv infusion
- 4 benefits with strong evidence, 2 moderate, 1 preliminary
- Half-life: 1-1.4 hours (parent compound), 75-80 hours (active metabolite OR-1896)
- 4 cited research studies in this guide
Mechanism of Action
Levosimendan enhances cardiac contractility through calcium sensitization of troponin C, increasing the calcium binding affinity without affecting intracellular calcium concentrations. Simultaneously, it opens ATP-sensitive potassium channels in vascular smooth muscle and myocardium, producing vasodilation and potential preconditioning effects. The compound also exhibits mild phosphodiesterase III inhibition, contributing to its inotropic and vasodilatory properties. Its active metabolite OR-1896 maintains similar mechanisms with extended duration.
Research Benefits
Levosimendan at a Glance
Levosimendan enhances cardiac contractility through calcium sensitization of troponin C, increasing the calcium binding affinity without affecting intracellular calcium concentrations.
Enhanced Cardiac Contractility
Strong EvidenceIncreases myocardial contractile force through troponin C calcium sensitization without raising oxygen consumption, improving stroke volume and cardiac output in failing hearts.
Vasodilation and Preload Reduction
Strong EvidenceOpens ATP-sensitive potassium channels in vascular smooth muscle, reducing systemic vascular resistance and venous return while maintaining coronary perfusion.
Improved Hemodynamic Parameters
Strong EvidenceReduces pulmonary capillary wedge pressure, increases cardiac index, and improves mixed venous oxygen saturation in acute heart failure models.
Sustained Hemodynamic Benefits
Strong EvidenceActive metabolite OR-1896 maintains cardiovascular improvements for 7-9 days after single infusion, extending therapeutic window beyond parent compound elimination.
Cardioprotective Effects
Moderate EvidenceProvides myocardial protection through KATP channel opening, potentially reducing ischemia-reperfusion injury and improving post-ischemic recovery.
Reduced Myocardial Oxygen Demand
Moderate EvidenceUnlike traditional inotropes, maintains or reduces myocardial oxygen consumption despite increased contractility, favorable for ischemic conditions.
Anti-Stunning Properties
PreliminaryMay accelerate recovery of myocardial function following stunning episodes through calcium sensitization and metabolic effects on cardiomyocytes.
Research Dosing Protocols
Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
| Research Protocol | Dose Range | Route |
|---|---|---|
| Acute heart failure studies | 0.05–0.2 mcg/kg/min | IV infusion |
| Cardiogenic shock research | 0.1–0.2 mcg/kg/min | IV infusion |
| Perioperative cardioprotection | 0.05–0.1 mcg/kg/min | IV infusion |
| Preconditioning studies | 6–12 mcg/kg | IV bolus |
Frequency
Continuous infusion for 24-72 hours or single bolus
Timing
Initiated at symptom onset or pre-procedure
Cycle Length
Single treatment cycle, effects sustained by active metabolite
Research Notes
- 1Loading dose of 6-24 mcg/kg over 10 minutes often precedes maintenance infusion
- 2Dose adjustment required in severe hepatic impairment
- 3Monitor blood pressure closely during infusion initiation
- 4Effects persist 7-9 days due to active metabolite formation
Reconstitution Guide
Standard Reconstitution
Vial Size
5 mg
Bacteriostatic Water
5 mL
Concentration
10 mcg
per 0.1 mL (10 units)
Step-by-Step Guide
Gather Materials
Levosimendan vial, bacteriostatic water, alcohol swabs, insulin syringes.
Equilibrate Temperature
Remove the vial from storage and allow it to reach room temperature (5-10 minutes).
Sanitize
Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.
Draw Water
Draw 5 mL of bacteriostatic water into a syringe.
Add Water to Vial
Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.
Mix Gently
Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.
Store Properly
Refrigerate at 2-8°C (refrigerated). 24 hours after dilution.
Storage Temperature
2-8°C (refrigerated)
Shelf Life
24 hours after dilution
Important Notes
- •Supplied as 2.5mg/ml concentrate for infusion
- •Dilute with 5% dextrose or normal saline to 0.025-0.05mg/ml
- •Protect from light during storage and administration
- •Do not mix with alkaline solutions
Levosimendan Dosing Calculator
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Levosimendan Reconstitution Calculator
Calculate concentration, syringe units, and doses per vial with auto-filled values →
Safety & Side Effects
Reported Side Effects
- !Hypotension (dose-dependent)
- !Tachycardia
- !Headache
- !Hypokalemia
- !Atrial fibrillation
- !Ventricular arrhythmias
- !Nausea and vomiting
- !Dizziness
- !Myocardial ischemia (in severe hypotension)
- !Insomnia
Potential Interactions
- ⚡Antihypertensive medications (enhanced hypotensive effects)
- ⚡Beta-blockers (may reduce inotropic response)
- ⚡Digoxin (potential for additive inotropic effects)
- ⚡Warfarin (possible anticoagulation enhancement)
- ⚡Diuretics (increased risk of hypokalemia)
Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.
Research Studies
The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.
Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE randomized trial
Randomized trial of 1327 patients showing levosimendan improved hemodynamics but did not reduce mortality compared to dobutamine in acute heart failure.
Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled trials
Meta-analysis of 45 trials with 5480 patients demonstrating reduced mortality with levosimendan compared to control treatments.
Cardioprotective effects of levosimendan pretreatment in patients undergoing coronary artery bypass surgery
Study of 102 patients showing levosimendan pretreatment reduced troponin release and improved postoperative cardiac function.
Levosimendan in cardiogenic shock complicating acute myocardial infarction
Clinical study demonstrating improved hemodynamics and survival in cardiogenic shock patients treated with levosimendan.
Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.
Frequently Asked Questions
Levosimendan enhances contractility through calcium sensitization rather than increasing intracellular calcium, avoiding the increased oxygen consumption and arrhythmogenic potential of traditional inotropes like dobutamine or milrinone.
While the parent compound has a half-life of 1-1.4 hours, its active metabolite OR-1896 provides sustained effects for 7-9 days after a single infusion, extending therapeutic benefits beyond the infusion period.
Levosimendan causes vasodilation and can lower blood pressure further. Careful monitoring is required, and loading doses may need to be reduced or omitted in hypotensive patients to minimize this risk.
Continuous cardiac monitoring, frequent blood pressure checks, electrolyte monitoring (especially potassium), and assessment of cardiac output parameters are essential during levosimendan administration.
Levosimendan may provide cardioprotective effects in ischemic conditions due to its ability to enhance contractility without increasing oxygen demand, but careful hemodynamic monitoring is required to prevent excessive hypotension.
Store concentrate at 2-8°C, protect from light, and dilute with compatible solutions to appropriate concentrations. Once diluted, use within 24 hours and maintain light protection during administration.
Severe hypotension, severe aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy, and severe renal or hepatic impairment are major contraindications due to the drug's hemodynamic effects.
Combinations require careful consideration due to potential additive effects. Beta-blockers may reduce inotropic response, while vasodilators can enhance hypotensive effects requiring dose adjustments.
Research & Educational Use Only
All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.