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- Title
009 LEVOSIMENDAN IMPAIRS ATP PRODUCTION BY LIMITATION OF ELECTRON TRANSPORT CHAIN FUNCTION FOLLOWED BY LOSS OF CA2+ RETENTION CAPACITY IN HEALTHY MYOCARDIAL MITOCHONDRIA AND DURING ISCHAEMIA REPERFUSION INJURY.
- Authors
Sommer, S.; Leistner, M.; Aleksic, I.; Schimmer, C.; Alhussini, K.; Leyh, R.G.
- Abstract
Objectives: Levosimendan (LS) mitigates myocardial insufficiency. The impact of LS on myocardial-mitochondrial function is unknown. Hence, we analysed for subsarcolemmal mitochondrial (SSM) function dependent from LS of rat hearts undergoing Langendorff perfusion with or without global ischaemia.Methods: Rat hearts divided into 4 study-groups were subjected to 30 min of reperfusion without (IR0/30) or with application of 8 mg LS over 20 min (LS-IR0/30). Experiments were repeated with hearts being subjected to 40 min of warm global ischaemia without (IR40/30) or with application of LS (LS-IR40/30). Myocardial function was determined by left-ventricular pressure (mean, max, dP/dT max), contractility and coronary flow. SSM were isolated and analysed regarding electron transport chain (ETC) function, ATP production, Ca2+-induced swelling and Ca2+ fluxes.Results: Ischaemia significantly suppressed (P < 0.04) and LS insignificantly improved myocardial function (LVPmax). Both ischaemia (P < 0.03) and LS (P < 0.02) inhibited ETC function at complexes I–V, II–V and IV resulting in a reduced ATP content and production (P < 0.003) (see Fig. 1). SSM demonstrated an increased susceptibility towards Ca2+-induced swelling after ischaemia (P < 0.005), an effect insignificantly ameliorated by LS. Interestingly, SSM Ca2+-retention capacity declined after ischaemia (P < 0.002) and LS (P <0.008). Ca2+ flux demonstrated delayed Ca2+uptake and increased Ca2+-induced Ca2+ liberation in presence of ischaemia but predominantly after LS and IR (P < 0.004).Conclusion: LS improved myocardial function at the expense of ETC function and ATP production. Loss of ATP might explain limited Ca2+-retention capacity and increased Ca2+-liberation of SSM. However, limitation of Ca2+-induced SSM swelling in presence of LS suggests cardioprotection due to reduction of IR-dependent cell death.
- Publication
Interactive Cardiovascular & Thoracic Surgery, 2014, Vol 19, Issue suppl_1, pS3
- ISSN
1569-9293
- Publication type
Article
- DOI
10.1093/icvts/ivu276.9