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      Sympatho–Vagal Dysfunction in Patients with End-Stage Lung Disease Awaiting Lung Transplantation

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          Abstract

          Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 ± 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 ± 16 years) were enrolled in a case–control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients.

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          Most cited references23

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          Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt.

          The powers of the low-frequency (LF) and high-frequency (HF) oscillations characterizing heart rate variability (HRV) appear to reflect, in their reciprocal relationship, changes in the state of the sympathovagal balance occurring during numerous physiological and pathophysiological conditions. However, no adequate information is available on the quantitative resolution of this methodology. We studied 22 healthy volunteers (median age, 46.5 years) who were subjected after a rest period to a series of passive head-up tilt steps randomly chosen from the following angles: 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 90 degrees. From the continuous ECG, after appropriate analog-to-digital conversion, a personal computer was used to compute, with an autoregressive methodology, time and frequency domain indexes of RR interval variability. Spectral and cross-spectral analysis with the simultaneously recorded respiratory signal excluded its contribution to LF. Age was significantly correlated to variance and to the absolute values in milliseconds squared of very-low-frequency (VLF), LF, and HF components. The tilt angle was correlated to both LF and HF (expressed in normalized units [nu]) and to the LF-to-HF ratio (r = .78, -.72, and .68; respectively). Lower levels of correlation were found with HF (in ms2) and RR interval. No correlation was present between tilt angle and variance, VLF, or LF (in ms2). Individual analysis confirmed that the use of nu provided the greatest consistency of results. Spectral analysis of HRV, using nu or LF-to-HF ratio, appears to be capable of providing a noninvasive quantitative evaluation of graded changes in the state of the sympathovagal balance.
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            Development of the new lung allocation system in the United States.

            This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.
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              Increased sympathetic nerve activity in pulmonary artery hypertension.

              This study tested the hypothesis that sympathetic nerve activity is increased in pulmonary artery hypertension (PAH), a rare disease of poor prognosis and incompletely understood pathophysiology. We subsequently explored whether chemoreflex activation contributes to sympathoexcitation in PAH. We measured muscle sympathetic nerve activity (MSNA) by microneurography, heart rate (HR), and arterial oxygen saturation (Sao(2)) in 17 patients with PAH and 12 control subjects. The patients also underwent cardiac echography, right heart catheterization, and a 6-minute walk test with dyspnea scoring. Circulating catecholamines were determined in 8 of the patients. Chemoreflex deactivation by 100% O(2) was assessed in 14 patients with the use of a randomized, double-blind, placebo-controlled, crossover study design. Compared with the controls, the PAH patients had increased MSNA (67+/-4 versus 40+/-3 bursts per minute; P<0.0001) and HR (82+/-4 versus 68+/-3 bpm; P=0.02). MSNA in the PAH patients was correlated with HR (r=0.64, P=0.006), Sao(2) (r=-0.53, P=0.03), the presence of pericardial effusion (r=0.51, P=0.046), and NYHA class (r=0.52, P=0.033). The PAH patients treated with prostacyclin derivatives had higher MSNA (P=0.009), lower Sao(2) (P=0.01), faster HR (P=0.003), and worse NYHA class (P=0.04). Plasma catecholamines were normal. Peripheral chemoreflex deactivation with hyperoxia increased Sao(2) (91.7+/-1% to 98.4+/-0.2%; P<0.0001) and decreased MSNA (67+/-5 to 60+/-4 bursts per minute; P=0.0015), thereby correcting approximately one fourth of the difference between PAH patients and controls. We report for the first time direct evidence of increased sympathetic nerve traffic in advanced PAH. Sympathetic hyperactivity in PAH is partially chemoreflex mediated and may be related to disease severity.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                17 April 2020
                April 2020
                : 9
                : 4
                : 1146
                Affiliations
                [1 ]Department of Internal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; eleonora.tobaldini@ 123456unimi.it (E.T.); giorgio.mantoan@ 123456studenti.unimi.it (G.M.); alice.monti@ 123456unimi.it (A.M.); giulia.coti@ 123456unimi.it (G.C.Z.); camilla.cirelli@ 123456unimi.it (C.C.)
                [2 ]Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
                [3 ]Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University, Niterói 24210-130, Brazil; gabrieldias@ 123456id.uff.br (G.D.R.); ppssoares@ 123456id.uff.br (P.P.d.S.S.)
                [4 ]Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; paolo.tarsia@ 123456policlinico.mi.it (P.T.); letizia.morlacchi@ 123456policlinico.mi.it (L.C.M.); valeria.rossetti@ 123456policlinico.mi.it (V.R.); stefano.aliberti@ 123456unimi.it (S.A.); francesco.blasi@ 123456unimi.it (F.B.)
                [5 ]Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
                [6 ]Thoracic Surgery and Lung Transplantation Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; ilaria.righi@ 123456policlinico.mi.it (I.R.); mario.nosotti@ 123456unimi.it (M.N.)
                Author notes
                [* ]Correspondence: nicola.montano@ 123456unimi.it ; Tel.: +39-025-503-5583
                [†]

                These authors contributed equally to the manuscript.

                Author information
                https://orcid.org/0000-0002-9258-2954
                https://orcid.org/0000-0002-0247-7756
                https://orcid.org/0000-0002-8571-121X
                https://orcid.org/0000-0001-9589-4294
                https://orcid.org/0000-0001-9206-0075
                https://orcid.org/0000-0002-0090-4531
                https://orcid.org/0000-0002-2285-9970
                Article
                jcm-09-01146
                10.3390/jcm9041146
                7230240
                32316428
                0113598b-cc1a-4e8b-a584-5adce3bc4cab
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 March 2020
                : 09 April 2020
                Categories
                Article

                heart rate variability,cardiac autonomic control,lung transplantation,spectral analysis,symbolic analysis,cardiac autonomic dysfunction,autonomic nervous system

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