Levosimendan Ameliorates Cardiopulmonary Function but Not Inflammatory Response in a Dual Model of Experimental ARDS

Q: What are the key findings of this study?

Intravenous levosimendan significantly improved hemodynamics and lung function (PaO2/FiO2 ratio) in a porcine model of early ARDS compared to milrinone and vehicle, though it did not conclusively reduce inflammatory response or lung injury.

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Acute respiratory distress syndrome (experimental porcine model) (n=20). Intervention: Levosimendan vs. Milrinone and Vehicle (Glucose 5%). Primary outcome: Hemodynamics and lung function (PaO2/FiO2 ratio and mean pulmonary arterial pressure) (p=<0.05).

Q: What question did this study set out to answer?

To examine whether intravenous levosimendan improves cardiopulmonary performance and reduces systemic and pulmonary inflammation in a porcine model of acute respiratory distress syndrome.

René Rissel; Moritz Gosling; Jens Kamuf; Miriam Renz; Robert Ruemmler; Alexander Ziebart; Erik K. Hartmann

doi:10.3390/biomedicines10051031

April 29, 2022BiomedicinesOpen Access

Levosimendan Ameliorates Cardiopulmonary Function but Not Inflammatory Response in a Dual Model of Experimental ARDS

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Key result

Levosimendan improves hemodynamics and oxygenation over milrinone in early ARDS without altering inflammation.

P<0.05
n=20

Figures

Why the study?

Levosimendan may exhibit anti-inflammatory properties, but whether it improves cardiopulmonary function and benefits the inflammatory response in ARDS required investigation.

Does intravenous levosimendan improve cardiopulmonary function and inflammatory response in a porcine model of ARDS compared to milrinone?

Key Points

To examine whether intravenous levosimendan improves cardiopulmonary performance and reduces systemic and pulmonary inflammation in a porcine model of acute respiratory distress syndrome.
Evaluated 20 swine (weight: 31.2 ± 1.2 kg) subjected to a dual-hit ARDS protocol combining oleic acid infusion and bronchoalveolar lavage.
Assigned animals to receive intravenous levosimendan (n = 8), milrinone (n = 8), or vehicle control (n = 4) over an 8-hour monitoring period.
Vehicle-treated animals required significantly higher minute ventilation at T8 compared to those receiving levosimendan (p < 0.031).
Plasma sRAGE and IL-6 levels showed only a trend toward suppression with levosimendan (p = 0.055), and lung wet-to-dry ratios showed no significant differences among levosimendan (6.3 ± 1.7), milrinone (7.5 ± 1.4), and vehicle (6.7 ± 1.3; p > 0.05).

Study Design

Type

RCT (n=20)

Blinding

Blinded observers

Randomization

Random generator

Multicenter

No

Structured PICO

Does intravenous levosimendan improve cardiopulmonary function and inflammatory response in a porcine model of ARDS compared to milrinone?

P

Population

20 healthy male pigs subjected to a double-hit experimental ARDS model and monitored for 8 hours.

I

Intervention

Levosimendan administered intravenously

C

Comparator

Milrinone

O

Outcome

Cardiopulmonary function (hemodynamics and lung function) and inflammatory responsesurrogate

Main Result

p-value: p=<0.05

Limitations

Difficulty determining whether lung injury was predominantly caused by lavage, oleic acid, or both.
Unclear translational significance of changes in pro- and anti-inflammatory cytokines from animals to humans.
Short experiment duration (8 hours) captures only early-stage ARDS, missing late pathological changes.
Lack of measurement of plasma concentrations of levosimendan and its active metabolite OR-1896 to distinguish their respective effects.

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Implication

Intravenous levosimendan improves cardiopulmonary hemodynamics but lacks significant anti-inflammatory effects in a porcine model of ARDS.

Abstract

The calcium sensitiser levosimendan, which is used as an inodilator to treat decompensated heart failure, may also exhibit anti-inflammatory properties. We examined whether treatment with levosimendan improves cardiopulmonary function and is substantially beneficial to the inflammatory response in acute respiratory response syndrome (ARDS). Levosimendan was administered intravenously in a new experimental porcine model of ARDS. For comparison, we used milrinone, another well-known inotropic agent. Our results demonstrated that levosimendan intravenously improved hemodynamics and lung function in a porcine ARDS model. Significant beneficial alterations in the inflammatory response and lung injury were not detected.

Discussion

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Cite This Study

Rissel et al. (2022) conducted an RCT in Acute respiratory distress syndrome (experimental porcine model) (n=20). Levosimendan vs. Milrinone and Vehicle (Glucose 5%) was evaluated on Hemodynamics and lung function (PaO2/FiO2 ratio and mean pulmonary arterial pressure) (p=<0.05). Intravenous levosimendan significantly improved hemodynamics and lung function (PaO2/FiO2 ratio) in a porcine model of early ARDS compared to milrinone and vehicle, though it did not conclusively reduce inflammatory response or lung injury.

synapsesocial.com/papers/6a2296d15954412fd5d2a78e https://doi.org/10.3390/biomedicines10051031

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Levosimendan Ameliorates Cardiopulmonary Function but Not Inflammatory Response in a Dual Model of Experimental ARDS

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Levosimendan Ameliorates Cardiopulmonary Function but Not Inflammatory Response in a Dual Model of Experimental ARDS

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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