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

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

doi:10.3390/biomedicines10051031

Cited by 5 publications

(2 citation statements)

References 47 publications

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“…Following approval of the state and institutional animal care committee (Landesuntersuchungsamt Rheinland-Pfalz, Koblenz, Germany; G16-1-015, G18-1-044, G20-1–135) eight male pigs ( Sus scrofa domesticus; weight 30 ± 2 kg, aged 8 to 12 weeks) were prospectively examined in the vehicle group in the past 2 years for one of the two used animal models and post-hoc compared in this study (G16-1-015 = 8 vehicle animals, ARDS induced with LPS; G18-1-044/G20-1-135 = 4 vehicle animals from each study, ARDS induced with the double-hit model). The results from one of the previous mentioned studies (G18-1-044) have already been published [ 8 ]. All the cited studies were prospectively performed in compliance with the ARRIVE guidelines [ 9 ].…”

Section: Methodsmentioning

confidence: 99%

Comparison of two porcine acute lung injury models: a post-hoc analysis

Rissel

Renz

Mohnke

et al. 2022

ICMx

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Background Acute respiratory distress syndrome (ARDS) is a common disease in intensive care medicine. Despite intensive research, mortality rates are high, not even in COVID-19 ARDS. Thereby, pigs offer some advantages to study the characteristics of ARDS. Many different ARDS models exist. Most of the articles published focused on histopathological and microscopic lung alterations to identify the most suitable animal ARDS model. “Macroscopic” observations and descriptions are often missing. Therefore, we performed a post-hoc comparison of two common ARDS models for pigs: lipopolysaccharide (LPS) vs. a double-hit model (bronchoalveolar lavage + oleic acid infusion). We investigated hemodynamic, spirometric and laboratory changes as another main clinical part of ARDS. Results The groups were compared by two-way analysis of variance (ANOVA) with a post-hoc Student–Newman–Keuls test. A p value lower than 0.05 was accepted as significant. All animals (n = 8 double-hit ARDS; n = 8 LPS ARDS) survived the observation period of 8 h. ARDS induction with reduced oxygen indices was successful performed in both models (76 ± 35/225 ± 54/212 ± 79 vs. 367 ± 64; T0/T4/T8 vs. BLH for double-hit; 238 ± 57/144 ± 59 vs. 509 ± 41; T4/T8 vs. BLH for LPS; p < 0.05). ARDS induced with LPS leads to more hemodynamic (mean arterial pulmonary pressure 35 ± 3/30 ± 3 vs. 28 ± 4/23 ± 4; T4/T8 LPS vs. double-hit; p < 0.05; doses of norepinephrine 1.18 ± 1.05 vs. 0.11 ± 0.16; LPS vs. double-hit for T8; p < 0.05) and inflammatory (pulmonary IL-6 expression: 2.41e−04 ± 1.08e−04 vs. 1.45e−05 ± 7.26e−06; LPS vs. double-hit; p < 0.05) alterations. ARDS induced by double-hit requires a more invasive ventilator strategy to maintain a sufficient oxygenation (PEEP at T4: 8 ± 3 vs. 6 ± 2; double-hit vs. LPS; p < 0.05). Conclusions Both animal ARDS models are feasible and are similar to human presentation of ARDS. If your respiratory research focus on hemodynamic/inflammation variables, the LPS-induced ARDS is a feasible model. Studying different ventilator strategies, the double-hit ARDS model offers a suitable approach.

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Section: Methodsmentioning

confidence: 99%

Comparison of two porcine acute lung injury models: a post-hoc analysis

Rissel

Renz

Mohnke

et al. 2022

ICMx

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“…Other studies [42,43] have suggested that levosimendan has an anti-inflammatory response that limits the production of chemokines and inflammatory cytokines. The anti-inflammatory effect prevents the activation and recruitment of immune cells during sepsis.…”

Section: E617mentioning

confidence: 99%

Meta-Analysis of the Efficacy of Levosimendan in the Treatment of Severe Sepsis Complicated with Septic Cardiomyopathy

Guan,

Zhang,

et al. 2023

HSF

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Introduction: Sepsis is a medical condition characterized by acute organ dysfunction and uncontrolled inflammation. Organ dysfunction in sepsis is the primary cause of mortality in patients with myocardial dysfunction. Levosimendan is a vasodilating and inotropic agent used in patients with acute heart failure and has resulted in decreased morbidity and mortality in these patients. Our main objective is to examine levosimendan's efficacy in treating severe sepsis complicated with septic cardiomyopathy. Methods: We systematically searched five databases, PubMed, Web of Science, Embase, Cochrane Library and BioMed Central, for articles and publications from their inception to 2023. Our study adopted the PICOS approach in identifying suitable publications during the systematic search. Inclusion criteria included randomized, controlled trials utilizing levosimendan in adult patients diagnosed with septic shock or severe sepsis. We excluded non-English publications and non-randomized controlled trials. The Newcastle-Ottawa scale (NOS) scale was used to assess the methodological quality, while the risk of bias was assessed through the Cochrane Risk of bias tool. All statistical analyses were performed using RevMan version 5.4. Results: Eight studies met the eligibility criteria and were included in the analysis. There was a statistically significant positive effect on cardiac input in patients treated with levosimendan compared to those treated with dobutamine (p < 0.001). Similarly, there were positive effects on left ventricular ejection fraction (LVEF) (p < 0.001) and left ventricular stroke work index (LVSWI) (p < 0.001). We observed a significant reduction in mortality (p < 0.01) and serum levels of lactic acid (p < 0.01). Discussion: Levosimendan is a calcium sensitizer associated with an influx of calcium ions and activation of ATP-dependent potassium channels that increases myocardial contractility contractions, enhances vasodilation and improves oxygen supply to the cells and tissues. Conclusion: Levosimendan is highly efficacious and safe in the management of sepsis and sepsis-induced cardiomyopathy.

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