1 b-adrenoceptors are important modulators of cardiac function. The present study investigated b 3 -adrenergic eNOS activation in human myocardium. 2 We measured nitric oxide (NO) liberation (diaminofluorescence) and signal transduction (immunohistochemistry, phosphorylation of eNOS Ser1177 , eNOS Thr495 , eNOS Ser114 , Akt/protein kinase B (Akt/PKB), and eNOS translocation) in human right atrial (RA, aortocoronary-bypass OP) and left ventricular nonfailing (LV, rejected donor hearts) myocardium after application of BRL 37344 (BRL), a preferential b 3 -adrenoceptor agonist. 3 In both RA and LV, BRL (10 ml) induced a liberation of NO. An eNOS activation via translocation was only observed in RA after application of BRL (10 mM). Yet, the NO liberation in both LV and RA was accompanied by phosphorylation of eNOS Ser1177 and Akt/PKB. BRL-induced eNOS phosphorylation was abolished by LY292004, a blocker of PI-3 kinase. eNOS-Ser 114 phosphorylation was unchanged in RA, but decreased in LV after b 3 -adrenergic stimulation. BRL did not alter phosphorylation of eNOS Thr495 . 4 In conclusion, receptor-dependent eNOS activation is differentially regulated in the human heart. In the left ventricle, eNOS activation via phosphorylation seems to be of major importance, whereas in human atrial myocardium eNOS translocation is the predominant mechanism induced by b 3 -adrenergic activation.
IntroductionPeripartum cardiomyopathy (PPCM) is a rare cardiomyopathy characterized by an acute reduction in left ventricular ejection fraction (LVEF). Sudden deaths during the course of PPCM are reported to be elevated, the underlying mechanisms remains unknown. The aim of the present multi-centre study was to evaluate the arrhythmia burden in a multi-centre approach in patients with PPCM using a wearable cardioverter/defibrillator (WCD).Methods and resultsForty-nine patients from 16 German centres with newly diagnosed PPCM and LVEF ≤35% receiving a WCD were included in this retrospective analysis. Mean follow-up was 15 ± 10 months. At diagnosis, mean age was 33 ± 5 years, parity was 2.1 ± 1.6, LVEF was 21 ± 7%, NYHA functional class was 3.4 ± 0.7. Mean wear time was 120 ± 106 days, mean wear time per day was 21.4 ± 3.3 h. Six (12%) patients presented eight ventricular tachyarrhythmias during WCD period: five episodes of VF, two sustained ventricular tachycardia (VT) and one non-sustained VT occurred.ConclusionThis multicentre study underpins the elevated risk for ventricular tachyarrhythmias in patients with newly diagnosed PPCM and reduced LVEF. A WCD should be considered for 3–6 months in these patients to prevent sudden cardiac death from ventricular tachyarrhythmias.
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