P5695Inhibition of PDE3 but not PDE4 phosphodiesterases stimulate ryanodine receptor phosphorylation at Ser2808

Jiménez-Sábado, Verónica; Herraiz‐Martínez, Adela; Nolla‐Colomer, Carme; Tarifa, Carmen; Vallmitjana, Alexander; Montiel, José; Benítez, Raúl; Cinca, Juan; Hove‐Madsen, Leif

doi:10.1093/eurheartj/ehy566.p5695

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“…A possible explanation of the detrimental effects of milrinone as it relates to ventricular arrhythmias in adults may be hyperphosphorylation of the ryanodine receptor, even when milrinone concentrations are reportedly within the 'therapeutic range'. 21 Furthermore, at higher milrinone dosing, there may be an 'offtarget' effect with inhibition of some phosphodiesterase type 4 isoforms that may promote heart failure and arrhythmias. 22,23 Arrhythmias after paediatric cardiac surgery are common, and…”

Section: Discussionmentioning

confidence: 99%

Circulating cyclic adenosine monophosphate concentrations in milrinone treated paediatric patients after congenital heart surgery

et al. 2021

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Background: Milrinone is a phosphodiesterase type 3 inhibitor that results in a positive inotropic effect in the heart through an increase in cyclic adenosine monophosphate. The purpose of this study was to evaluate circulating cyclic adenosine monophosphate and milrinone concentrations in milrinone treated paediatric patients undergoing congenital heart surgery. Methods: Single-centre prospective observational pilot study from January 2015 to December 2017 including children aged birth to 18 years. Milrinone and circulating cyclic adenosine monophosphate concentrations were measured at four time points through the first post-operative day and compared between patients with and without low cardiac output syndrome, defined using clinical and laboratory criteria. Results: Fifty patients were included. Nine (18%) developed low cardiac output syndrome. For all patients, 22% had single ventricle heart disease. The density and distribution of cyclic adenosine monophosphate concentrations varied between those with and without low cardiac output syndrome but were not significantly different. Milrinone concentrations increased in all patients. Paired t-tests demonstrated an increase in circulating cyclic adenosine monophosphate concentrations during the post-operative period among patients without low cardiac output syndrome. Conclusions: In this prospective observational study, circulating cyclic adenosine monophosphate concentrations increased in those without low cardiac output syndrome during the first 24 post-operative hours and milrinone concentrations increased in all patients. Further study of the utility of cyclic adenosine monophosphate concentrations in milrinone treated patients is necessary.

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Section: Discussionmentioning

confidence: 99%