Myocardial Response to Milrinone in Single Right Ventricle Heart Disease
Myocardial Response to Milrinone in Single Right Ventricle Heart Disease
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DOI：
10.1016/j.jpeds.2016.04.009
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发表时间：
2016-07-01
影响因子：
5.1
通讯作者：
Miyamoto, Shelley D.
中科院分区：
文献类型：
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作者：
Nakano, Stephanie J.;Nelson, Penny;Miyamoto, Shelley D.
目的米力农是一种磷酸二酯酶（PDE）3抑制剂，经验性治疗右心室（RV）形态（SRV）的单心室心脏病已越来越普遍;我们的目的是描述患有SRV的儿童群体中对PDE 3抑制（PDE 3 i）的心肌反应。研究设计环磷酸腺苷水平，PDE活性，和磷酸化受磷蛋白（PLN）的测定，从非衰竭的儿童供体（n = 10）和儿童患者移植继发于SRV的人心室肌。根据PDE 3 i治疗对SRV患者进行进一步分类（n = 13，PDE 3 i组，n = 12，非PDE 3 i组）。结果与非衰竭RV心肌（n = 8）相比，用PDE 3 i治疗的SRV患者环磷酸腺苷水平较低（n = 12，P = 0.021）。慢性PDE 3 i不改变SRV心肌中的总PDE或PDE 3活性。与非衰竭的RV心肌相比，SRV心肌（无论有和没有PDE 3 i）表现出等效的磷酸化PLN在蛋白激酶A磷酸化site.Conclusions作为证据，保存磷酸化PLN，与SRV相关的分子适应显着不同，因为在小儿心脏衰竭，因为扩张型心肌病。这些改变支持了SRV儿科患者心力衰竭的病理生理学独特机制，这对该人群中PDE 3 i治疗的假定应答有直接影响。
Objectives Empiric treatment with milrinone, a phosphodiesterase (PDE) 3 inhibitor, has become increasingly common in patients with single ventricle heart disease of right ventricular (RV) morphology (SRV); our objective was to characterize the myocardial response to PDE3 inhibition (PDE3i) in the pediatric population with SRV.Study design Cyclic adenosine monophosphate levels, PDE activity, and phosphorylated phospholamban (PLN) were determined in explanted human ventricular myocardium from nonfailing pediatric donors (n = 10) and pediatric patients transplanted secondary to SRV. Subjects with SRV were further classified by PDE3i treatment (n = 13 with PDE3i and n = 12 without PDE3i).Results In comparison with nonfailing RV myocardium (n = 8), cyclic adenosine monophosphate levels are lower in patients with SRV treated with PDE3i (n = 12, P = .021). Chronic PDE3i does not alter total PDE or PDE3 activity in SRV myocardium. Compared with nonfailing RV myocardium, SRV myocardium (both with and without PDE3i) demonstrates equivalent phosphorylated PLN at the protein kinase A phosphorylation site.Conclusions As evidenced by preserved phosphorylated PLN, the molecular adaptation associated with SRV differs significantly from that demonstrated in pediatric heart failure because of dilated cardiomyopathy. These alterations support a pathophysiologically distinct mechanism of heart failure in pediatric patients with SRV, which has direct implications regarding the presumed response to PDE3i treatment in this population.