Sex-related differences in plasma amino acids of patients with ST-elevation myocardial infarction and glycine as risk marker of acute heart failure with preserved ejection fraction

Nowadays, the problem of preventing acute heart failure (AHF) in patients with ST-elevation myocardial infarction (STEMI) and preserved left-ventricular ejection fraction (pLVEF) is still not completely resolved, especially in late-presented patients. The purpose of study was: (1) assessment of free plasma amino acid (PAA) alterations in STEMI patients [not receiving reperfusion therapy (RT)], depending on sex and LVEF; (2) analysis of development of late/persistent AHF more than 48 h after admission (pAHF) in STEMI patients with pLVEF depending on PAA levels. This prospective cohort study included 92 STEMI patients (33 women and 59 men), not receiving RT. The free PAA were investigated by ion-exchange liquid-column chromatography. The women had significantly higher PAA levels than men in general cohort and cohort with pLVEF (n?=?69). There were associations between female sex and pAHF in general cohort (OR 3.7, p?=?0.004) and cohort with pLVEF (OR 11.4, p?=?0.0001) by logistic regression. The association between pAHF and glycine level [OR 2.5, p?<?0.0001; AUC 0.84, p?<?0.0001; 86.7% sensitivity and 77.8% specificity for?>?2.6 mg/dL] was revealed in cohort with pLVEF (including female and male). Glycine remained a predictor of pAHF with pLVEF by multivariable logistic regression adjusting for comorbidities, demographic and clinical variables. Higher rate of pAHF in female than in male STEMI patients with pLVEF is associated with higher plasma glycine in women. The glycine level may be genetically determinated by female sex. The plasma glycine?>?2.6 mg/dL is a predictor of pAHF in STEMI with pLVEF (including female and male).

     

Repeated Immobilization Stress Increases the Binding of c-Fos-Like Proteins to a Rat Dopamine β-Hydroxylase Promoter Enhancer Sequence

Abstract: The present study addressed the possibility that disinhibition of serotonin (5-HT) autoreceptor-mediated negative feedback might potentiate the elevation of nerve terminal 5-HT output induced by selective 5-HT reuptake blockade. To this end, rats were given citalopram and the 5-HT autoreceptor-blocking agents ( S )-UH-301 (5-HT_1A) and (−)-penbutolol (5-HT_1A/1B), and the effect on extracellular 5-HT in the ventral hippocampus was monitored by means of in vivo microdialysis. Citalopram (5 mg/kg, s.c.) approximately doubled the 5-HT output, a response that was markedly augmented by ( S )-UH-301 (3 mg/kg, s.c.) and (−)-penbutolol (8 mg/kg, s.c.) and by combined treatment with ( S )-UH-301 (3 mg/kg, s.c.) plus (−)-penbutolol (1 μ M ; via the dialysis perfusion medium), but not by (−)-penbutolol (1 μ M ) alone. These findings provide evidence that 5-HT, in particular 5-HT_1A, autoreceptor-mediated negative feedback mechanisms are pivotal in determining the nerve terminal 5-HT output level after 5-HT reuptake inhibition. These findings have important implications for the interplay between different processes controlling 5-HT transmission in vivo and might possibly offer a lead toward novel, therapeutically exploitable principles.