Impact of early levosimendan administration in patients with decompensated chronic heart failure on oxidative stress parameters — the rationale and study design
Abstract
Oxidative stress plays a key role in the development of heart failure. The study is a phase III, single-centre,
randomized, double-blind, clinical trial that assesses the influence of early intravenous levosimendan
administration in patients with decompensated CHF on oxidative stress parameters and the function of
enzymatic antioxidative mechanisms. A total of 50 patients with diagnosed CHF with reduced ejection
fraction, LVEF ≤ 35% are randomized in a 1:1 ratio to receive either levosimendan or dobutamine. The
hypothesis is that levosimendan in patients with decompensated heart failure may reduce ROS production
and/or enhance antioxidant protection. MDA and LPO concentrations and the activity of antioxidant
enzymes SOD, GPX, GR, and CAT will be measured in plasma samples.
Keywords: oxidative stressdecompensated chronic heart failurelevosimendandobutamine
References
- Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012; 24(5): 981–990.
- Singal PK, Khaper N, Palace V, et al. The role of oxidative stress in the genesis of heart disease. Cardiovasc Res. 1998; 40(3): 426–432.
- Keith M, Geranmayegan A, Sole MJ, et al. Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol. 1998; 31(6): 1352–1356.
- Pall ML. The NO/ONOO-cycle as the central cause of heart failure. Int J Mol Sci. 2013; 14(11): 22274–22330.
- Krupa W, Rozwodowska M, Sielski S, et al. Influence of cardiac resynchronization therapy on oxidative stress markers in patients with chronic heart failure. Cardiol J. 2014; 21(5): 576–582.
- Moris D, Spartalis M, Spartalis E, et al. The role of reactive oxygen species in the pathophysiology of cardiovascular diseases and the clinical significance of myocardial redox. Ann Transl Med. 2017; 5(16): 326.
- Tsutsui H. Oxidative stress in heart failure: the role of mitochondria. Intern Med. 2001; 40(12): 1177–1182.
- Grieve DJ, Shah AM. Oxidative stress in heart failure. More than just damage. Eur Heart J. 2003; 24(24): 2161–2163.
- López Farré A, Casado S. Heart failure, redox alterations, and endothelial dysfunction. Hypertension. 2001; 38(6): 1400–1405.
- McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021; 42(36): 3599–3726.
- Nieminen MS, Akkila J, Hasenfuss G, et al. Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J Am Coll Cardiol. 2000; 36(6): 1903–1912.
- Follath F, Cleland JGF, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet. 2002; 360(9328): 196–202.
- Rodríguez-González R, Pollesello P, Baluja A, et al. Effects of levosimendan on inflammation and oxidative stress pathways in a lipopolysaccharide-stimulated human endothelial cell model. Biol Res Nurs. 2019; 21(5): 466–472.
- Kubica J, Pstrągowski K, Kubica A, et al. Early administration of LEvosimendan in Patients witH decompensAted chroNic hearT failure (ELEPHANT) study. Rationale and protocol of the study. Medical Research Journal. 2023; 8(2): 91–95.
- Kopustinskiene DM, Pollesello P, Saris NEL. Potassium-specific effects of levosimendan on heart mitochondria. Biochem Pharmacol. 2004; 68(5): 807–812.
- Grossini E, Molinari C, Pollesello P, et al. Levosimendan protection against kidney ischemia/reperfusion injuries in anesthetized pigs. J Pharmacol Exp Ther. 2012; 342(2): 376–388.
- Basel H, Kavak S, Demir H, et al. Effect of levosimendan injection on oxidative stress of rat myocardium. Toxicol Ind Health. 2013; 29(5): 435–440.
- Avgeropoulou C, Andreadou I, Markantonis-Kyroudis S, et al. The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine. Eur J Heart Fail. 2005; 7(5): 882–887.