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dc.contributor.authorBisch, Alexander L
dc.contributor.authorWheatley, Courtney M
dc.contributor.authorBaker, Sarah E
dc.contributor.authorPeitzman, Elizabeth R
dc.contributor.authorVan Iterson, Erik H
dc.contributor.authorLaguna, Theresa A
dc.contributor.authorMorgan, Wayne J
dc.contributor.authorSnyder, Eric M
dc.date.accessioned2019-08-21T21:25:46Z
dc.date.available2019-08-21T21:25:46Z
dc.date.issued2019-03-29
dc.identifier.citationBisch, A. L., Wheatley, C. M., Baker, S. E., Peitzman, E. R., Van Iterson, E. H., Laguna, T. A., ... & Snyder, E. M. (2019). Cystic Fibrosis Transmembrane Conductance Regulator Genotype, Not Circulating Catecholamines, Influences Cardiovascular Function in Patients with Cystic Fibrosis. Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, 13, 1179548419835788.en_US
dc.identifier.issn1179-5484
dc.identifier.pmid30956528
dc.identifier.doi10.1177/1179548419835788
dc.identifier.urihttp://hdl.handle.net/10150/633913
dc.description.abstractBACKGROUND: Cystic fibrosis (CF) is a genetic disease affecting multiple organ systems of the body and is characterized by mutation in the gEne coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Previous work has shown that a single dose of a beta-agonist increases cardiac output (Q) and stroke volume (SV) and decreases systemic vascular resistance (SVR) in healthy subjects. This effect is attenuated in patients with CF; however, the mechanism is unknown. Potential explanations for this decreased cardiovascular response to a beta-agonist in CF include inherent cardiovascular deficits secondary to the CFTR mutation, receptor desensitization from prolonged beta-agonist use as part of clinical care, or inhibited drug delivery to the bloodstream due to mucus buildup in the lungs. This study sought to determine the effects of endogenous epinephrine (EPI) and norepinephrine (NE) on cardiovascular function in CF and to evaluate the relationship between cardiovascular function and CFTR F508del mutation. METHODS: A total of 19 patients with CF and 31 healthy control subjects completed an assessment of Q (C2H2 rebreathing), SV (calculated from Q and heart rate [HR]), Q and SV indexed to body surface area (BSA. Ql. and SVI. respectively). SVR (through assessment of Q and mean arterial blood pressure [MAP]). and HR (from 12-lead electrocardiogram [ECG]) at rest along with plasma measures of EPI and NE. We compared subjects by variables of cardiovascular function relative to EPI and NE, and also based on genetic variants of the F508del mutation (homozygous deletion for F508del. heterozygous deletion for F508del, or no deletion of F508del). RESULTS: Cystic fibrosis patients demonstrated significantly lower BSA (CF = 1.71 +/- 0.05 m(2) vs healthy = 1.84 +/- 0.04 m(2), P = .03) and SVI (CF = 30.6 +/- 2.5 mL/beat/m(2) vs healthy = 39.9 +/- 2.5 mL/beat/m(2) , P = .02) when compared with healthy subjects. Cystic fibrosis patients also demonstrated lower Q (CF = 4.58 +/- 0.36 L/min vs healthy = 5.71 +/- 0.32 L/min, P = .03) and SV (CF = 54 +/- 5.5 mL/beat vs healthy = 73.3 +/- 4.5 mL/beat. P = .01), and a higher HR (CF = 93.2 +/- 3.9 bpm vs healthy = 80.5 +/- 2.7 bpm, P < .01) and SVR (CF = 2082 +/- 156 dynes(*)s/cm(-5) vs healthy = 1616 +/- 74 dynes*s/cm(-5), P= .01) compared with healthy subjects. Furthermore. CF patients demonstrated a lower SV (P < .01) corrected for NE when compared with healthy subjects. No significant differences were seen in HR or Q relative to NE. or SVR relative to EPI. Differences were seen in SV(F-(2,F-14) = 7.982, P < .01) and SV index (F-(2(,14)) = 2.913, P = .08) when patients with CF were stratified according to F508del mutation (number of deletions). CONCLUSIONS: Individuals with CF have lower cardiac and peripheral hemodynamic function parameters at rest. Furthermore, these results suggest that impairment in cardiovascular function is likely the result of F508del CFTR genotype, rather than receptor desensitization or inhibited drug delivery.en_US
dc.description.sponsorshipNIH [HL 108962-01]en_US
dc.language.isoenen_US
dc.publisherSAGE PUBLICATIONS LTDen_US
dc.rightsCopyright © The Author(s) 2019. Article reuse guidelines: sagepub.com/journals-permissions. Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).en_US
dc.subjectF508delen_US
dc.subjectcardiovascular functionen_US
dc.subjectcatecholaminesen_US
dc.subjectcystic fibrosis transmembrane conductance regulatoren_US
dc.titleCystic Fibrosis Transmembrane Conductance Regulator Genotype, Not Circulating Catecholamines, Influences Cardiovascular Function in Patients with Cystic Fibrosisen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Arizona Resp Ctren_US
dc.identifier.journalCLINICAL MEDICINE INSIGHTS-CIRCULATORY RESPIRATORY AND PULMONARY MEDICINEen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleClinical medicine insights. Circulatory, respiratory and pulmonary medicine
refterms.dateFOA2019-08-21T21:25:47Z


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