CFTR Genotype, Not Circulating Catecholamines, Influence Cardiovascular Function in Cystic Fibrosis
2015-07
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CFTR Genotype, Not Circulating Catecholamines, Influence Cardiovascular Function in Cystic Fibrosis
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2015-07
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Objective: Cystic fibrosis (CF) is a genetic disease that elicits affects throughout the body and is characterized by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) with direct, well-documented, pulmonary function consequences. It has been shown 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 CF subjects; however, it is unknown if this decreased cardiovascular response to an inhaled drug is due to inherent cardiovascular deficits from CFTR mutation, receptor desensitization from prolonged Beta- agonist use, or inhibited drug delivery to the blood stream 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 cardiovascular function according to CFTR mutation [Delta]F508 Ins/DEL). Methods: Eleven CF subjects and 27 healthy control participants completed a cycle ergometery test with measures of Q, SV, SVR, and HR 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 [Delta]F508 Ins/DEL. Results: CF subjects demonstrated significantly lower Q and SV at 50% of peak exercise and peak exercise than healthy subjects, and a higher SVR at rest, 50% of peak, and peak exercise. Additionally, CF subjects also demonstrated significantly lower Q and SV relative to NE at rest, however there were no differences in HR relative to NE or SVR relative to EPI. When SV was stratified for CFTR mutation type, there were significant differences at rest, 50% of peak exercise, and there was a trend towards significance at peak exercise. Subjects with a double deletion of the [Delta]F508 had lower SV when compared to single deletion subjects. There were moderate and significant correlations found between EPI and SV and EPI and Q, but not in EPI and SVR when the study population was evaluated as a whole. Within the healthy group, there were significant correlations between EPI and SV, and EPI and Q, but none between EPI and SVR. Only correlations between EPI and Q were seen in the CF group. Conclusion: These results demonstrate that CF subjects have lower cardiovascular function parameters. Further, these results suggest that this impairment in cardiovascular function is likely the result of impairment in CFTR function due to CFTR genotype differences of the [Delta]F508, rather than receptor desensitization or inhibited drug delivery.
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University of Minnesota M.S. thesis. July 2015. Major: Kinesiology. Advisor: Eric Snyder. 1 computer file (PDF); ix, 48 pages.
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Bisch, Alexander. (2015). CFTR Genotype, Not Circulating Catecholamines, Influence Cardiovascular Function in Cystic Fibrosis. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/174743.
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