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      Role of sympathetic cotransmitter galanin on autonomic balance in heart failure: an active player or a bystander?

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          Abstract

          Objective:

          Galanin, a cotransmitter similar to neuropeptide Y (NPY), aggravates autonomic imbalance in systolic heart failure (HF) by attenuating vagal tonus after burst sympathetic activity. In animal HF models, galanin antagonists have improved cardiac function. To determine whether galanin is a promising therapeutic target in HF, we studied its concentrations in HF patients and evaluated its correlation with NPY, markers of humoral activity such as pro-BNP and copeptin, and echocardiographic parameters of HF severity.

          Methods:

          After recording demographic and echocardiographic characteristics of 87 individuals (57 HF patients and 30 control subjects), fasting serum concentrations of galanin, NPY, copeptin, and pro-BNP were determined.

          Results:

          Unlike pro-BNP, copeptin, and NPY, which were significantly elevated in HF patients (p<0.001, p<0.001, and p=0.001, respectively), galanin was similar in HF patients and control subjects (p=0.9). NPY correlated with the echocardiographic parameters of HF severity (r=–0.22, p=0.03 for EF; r=0.3, p=0.005 for Tei index of RV; r=–0.23, p=0.03 for TAPSE; and r=0.24, p=0.024 for E/e¢) and pro-BNP (r=0.22, p=0.046). NPY levels were also associated with beta blocker (BB) use, wherein BB significantly decreased NPY in both HF patients and control subjects. Galanin correlated with humoral biomarkers, pro-BNP and copeptin (r=0.39, p<0.001 and r=0.41, p<0.001, respectively). Although current smoking, BB therapy, pro-BNP, copeptin, and body mass index were associated with galanin in univariate analyses, the multiple linear regression model revealed that pro-BNP was the only significant determinant of galanin levels in HF patients.

          Conclusion:

          Our findings confirmed the role of NPY in autonomic balance and suggest that galanin is associated with the proadrenergic state, but its role in HF in humans remains unclear.

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          Most cited references23

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          New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function--a study in normals and dilated cardiomyopathy.

          Because systolic and diastolic dysfunction frequently coexist, it is hypothesized that a combined measure of left ventricular chamber performance may be more reflective of overall cardiac dysfunction than systolic or diastolic measures alone. METHODS Study patients consisted of 170 subjects: 70 normals, 47 patients with severe dilated cardiomyopathy in NYHA class III-IV awaiting cardiac transplantation and 53 patients with idiopathic dilated cardiomyopathy of intermediate severity [NYHA class II, ejection fractions (EF) 30-50%]. EF, stroke volume and cardiac indexes were measured using conventional echo-Doppler methods. Pre-ejection period/ejection time (PEP/ET), isovolumetric relaxation time (IRT), isovolumetric contraction time/ET (ICT/ET) were also measured. A new derived index of myocardial performance: (ICT+IRT)/ET, was obtained by subtracting ET from the interval between cessation and onset of the mitral inflow velocity to give the sum of ICT and IRT. RESULTS The index was easily measured, reproducible, and had a narrow range in normals. The mean value of the index was significantly different between normal, intermediate and pre-transplant subjects (0.39 +/- 0.05, 0.59 +/- 0.10 and 1.06 +/- 0.24, respectively, p < 0.001 for all comparisons). The degree of inter-group overlap was smaller for the index compared to PEP/ET, ICT/ET and other parameters. Within functional groups, the value of the index did not appear to be related to heart rate, mean arterial pressure and the degree of mitral regurgitation. CONCLUSION (ICT+IRT)/ET is a conceptually new, simple and reproducible Doppler index of combined systolic and diastolic myocardial performance in patients with primary myocardial systolic dysfunction.
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            Vagus Nerve Stimulation for the Treatment of Heart Failure: The INOVATE-HF Trial.

            Heart failure (HF) is increasing in prevalence and is a major cause of morbidity and mortality despite advances in medical and device therapy. Autonomic imbalance, with excess sympathetic activation and decreased vagal tone, is an integral component of the pathophysiology of HF.
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              Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity.

              Galanin was first identified 30 years ago as a "classic neuropeptide," with actions primarily as a modulator of neurotransmission in the brain and peripheral nervous system. Other structurally-related peptides-galanin-like peptide and alarin-with diverse biologic actions in brain and other tissues have since been identified, although, unlike galanin, their cognate receptors are currently unknown. Over the last two decades, in addition to many neuronal actions, a number of nonneuronal actions of galanin and other galanin family peptides have been described. These include actions associated with neural stem cells, nonneuronal cells in the brain such as glia, endocrine functions, effects on metabolism, energy homeostasis, and paracrine effects in bone. Substantial new data also indicate an emerging role for galanin in innate immunity, inflammation, and cancer. Galanin has been shown to regulate its numerous physiologic and pathophysiological processes through interactions with three G protein-coupled receptors, GAL1, GAL2, and GAL3, and signaling via multiple transduction pathways, including inhibition of cAMP/PKA (GAL1, GAL3) and stimulation of phospholipase C (GAL2). In this review, we emphasize the importance of novel galanin receptor-specific agonists and antagonists. Also, other approaches, including new transgenic mouse lines (such as a recently characterized GAL3 knockout mouse) represent, in combination with viral-based techniques, critical tools required to better evaluate galanin system physiology. These in turn will help identify potential targets of the galanin/galanin-receptor systems in a diverse range of human diseases, including pain, mood disorders, epilepsy, neurodegenerative conditions, diabetes, and cancer. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
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                Author and article information

                Journal
                Anatol J Cardiol
                Anatol J Cardiol
                Anatolian Journal of Cardiology
                Kare Publishing (Turkey )
                2149-2263
                2149-2271
                October 2017
                11 August 2017
                : 18
                : 4
                : 281-288
                Affiliations
                [1]Department of Cardiology, Faculty of Medicine, Namık Kemal University; Tekirdağ- Turkey
                [* ]Department of Degree of Science, Faculty of Medicine, Namık Kemal University; Tekirdağ- Turkey
                [** ]Department of Biochemistry, Faculty of Medicine, Namık Kemal University; Tekirdağ- Turkey
                Author notes
                Address for correspondence: Dr. Demet Özkaramanlı Gür, Namık Kemal Üniversitesi Tıp Fakültesi Kardiyoloji Anabilim Dalı, 3. Zemin, Değirmenaltı yerleşkesi, Tekirdağ- Türkiye E-mail: dozkarm@ 123456yahoo.com
                Article
                AJC-18-281
                10.14744/AnatolJCardiol.2017.7831
                5731524
                28811392
                7f5f51f2-aec8-4a91-b191-882a99bb64f1
                Copyright: © 2017 Turkish Society of Cardiology

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

                History
                : 08 June 2017
                Categories
                Original Investigation

                heart failure,galanin,neuropeptide y,sympathovagal crosstalk

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