Influence of Circulating Catecholamines on Cardiovascular Function at Rest and During Exercise in Cystic Fibrosis

Abstract

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) lead to altered ion regulation, resulting in CF. CFTR also plays an important role in cardiac function. We have shown that β‐agonist inhalation results in increased cardiac output (Q), stroke volume (SV), and decreased systemic vascular resistance (SVR) in healthy humans, suggesting stimulation of the β‐adrenergic receptors via inhalation. We have also shown that this cardiovascular (CV) response is attenuated in CF, which could be due to receptor desensitization or inhibited drug delivery to the blood stream due to mucus build‐up. This study sought to determine the effects of epinephrine (EPI) and norepinephrine (NE) on CV function in CF. 11 CF patients and 27 controls completed a cycle ergometery test with measures of Q, SV, SVR, and HR along with EPI and NE. CF patients had lower Q corrected for NE at 50% and peak exercise (rest: Q/NE= 0.012 ±0.002 vs 0.017 ±0.002; 50%: Q/NE= 0.026 ±0.004 vs 0.045 ±0.004; peak: Q/NE= 0.03 ±0.004 vs 0.05 ±0.005, CF vs healthy, p<0.05) and lower SV corrected for NE at rest, 50%, and peak (rest: SV/NE= 0.12 ±0.03 vs 0.22 ±0.02; 50%: SV/NE= 0.17 ±0.04 vs 0.32 ±0.03; peak: SV/NE= 0.18 ±0.04 vs 0.35 ±0.03, CF vs healthy, p<0.05), no difference in SVR when corrected for EPI (rest: SVR/EPI= 53 ±13 vs 33 ±4; 50%: SVR/EPI= 28 ±7 vs 15 ±2; peak: SVR/EPI= 22 ±5 vs 15 ±3; in CF vs healthy). These results suggest that CF patients have lower cardiac function relative to circulating NE, no difference in SVR relative to EPI, indicating impairment in cardiac function, likely as a result from a loss of CFTR function.