ArticlePloS one2015
A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Ventriculo-arterial coupling for predicting cardiac index increase in infants after heart surgery.Interdisciplinary cardiovascular and thoracic surgery · 2023Article
- The role of landiolol in the management of atrial tachyarrhythmias in patients with acute heart failure and cardiogenic shock: case reports and review of literature.European heart journal supplements : journal of the European Society of Cardiology · 2022Article
- Negative inotropic mechanisms of β-cardiotoxin in cardiomyocytes by depression of myofilament ATPase activity without activation of the classical β-adrenergic pathway.Scientific reports · 2021Article
- Peculiar Aspects of Patients with Inherited Arrhythmias during the COVID-19 Pandemic.Arquivos brasileiros de cardiologia · 2021Review
- SARS-CoV-2, COVID-19, and inherited arrhythmia syndromes.Heart rhythm · 2020Review
- Suppression of cardiac memory-related severe form of torsades de pointes by landiolol in a patient with congenital long QT syndrome type 2.HeartRhythm case reports · 2020Article
- Evaluating the Therapeutic Efficacy and Safety of Landiolol Hydrochloride for Management of Arrhythmia in Critical Settings: Review of the Literature.Vascular health and risk management · 2020Review
- LncRNACirculation research · 2018Article
- Landiolol suppression of electrical storm of torsades de pointes in patients with congenital long-QT syndrome type 2 and myocardial ischemia.Journal of arrhythmia · 2017Article
- Practical applicability of landiolol, an ultra-short-acting β1-selective blocker, for rapid atrial and ventricular tachyarrhythmias with left ventricular dysfunction.Journal of arrhythmia · 2016Article
- Article
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Authors and funding
18 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
objectivesThe purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism.
backgroundThe molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+) handling in heart failure remains unclear.
methodsWe investigated the effect of milrinone plus landiolol on intracellular Ca(2+) transient (CaT), cell shortening (CS), the frequency of diastolic Ca(2+) sparks (CaSF), and sarcoplasmic reticulum Ca(2+) concentration ({Ca(2+)}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB).
resultsIn failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+)}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+)}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes.
conclusionA low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+) leak.
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