Skeletal muscle oxidative capacity in patients with cystic fibrosis

Abstract

Introduction Exercise intolerance predicts mortality in patients with cystic fibrosis (CF); however, the mechanisms have yet to be fully elucidated. Using near infrared spectroscopy (NIRS), this study compared skeletal muscle oxidative capacity in patients with CF to healthy controls. Methods Thirteen patients and 16 demographically-matched controls participated in this study. NIRS was utilized to measure the recovery rate of oxygen consumption (musVO2max) of the vastus lateralis muscle after 15 s of electrical stimulation (4 Hz) and subsequent repeated transient arterial occlusions. Results musVO2max was reduced in patients with CF (1.82 ± 0.4 min−1) compared to controls (2.13 ± 0.5 min−1, p = 0.04). A significant inverse relationship between age and musVO2max was observed in patients (r = −0.676, p = 0.011), but not controls (r = −0.291, p = 0.274). Discussion Patients with CF exhibit a reduction in skeletal muscle oxidative capacity compared to controls. It appears as the reduced skeletal muscle oxidative capacity is accelerated by age and could likely contribute to exercise intolerance in patients with CF.

The Coupling of Peripheral Blood Pressure and Ventilatory Responses during Exercise in Young Adults with Cystic Fibrosis

“…However, and perhaps equally important, while others have illustrated that with as a ratio or slope during CPET may be increased in adolescent or adult CF [12–14, 23, 50], we demonstrate for the first time that increased blood pressure during CPET is directly related to elevated ventilation and, hence, appearing as an important contributor to augmented slope in adult CF. As such, consistent with observations and hypotheses of others [8, 12–14, 18–24], these data suggest compared to , understanding the mechanisms of low ventilatory efficiency (e.g., high slope) may be equally important in elucidating the origins poor exercise capacity in CF. With this, new and noteworthy, in a complementary manner that extends emerging work in this field questioning peripheral vascular function in CF [19–21, 24, 36], these data suggest unresolved pathways involved in peripheral blood pressure function may serve an important role in contributing to abnormal ventilatory and gas-exchange responses to exercise in CF.…”

“…Although CF is commonly recognized as a genetic disease manifesting within the pulmonary system and primarily affecting pulmonary function, an accumulating body of evidence suggests the traditional paradigm linking reduced pulmonary function to decreased aerobic exercise capacity should also now consider integrated non-pulmonary factors as important contributors to this prognostic indicator in CF [8, 10–14, 18–25]. With this, observations from this study are consistent with the hypothesis that CF demonstrate a disease phenotype that extends beyond the lungs to cardiac, peripheral vascular, and skeletal muscle organ systems [8, 12–14, 18–25]. …”

“…Augmented blood pressure during exercise as a result of impaired vasodilation, arterial stiffness, and/or exaggerated sympathetically-mediated vasoconstriction is complex with the potential of leading to, or being the consequence of numerous effects at the local skeletal muscle level in CF [12, 18, 22, 23, 25]. For example, impaired sympatholysis may lead to decreased perfusion and convective delivery of oxygen to metabolically active skeletal tissue, resulting in and/or contributing to attenuated oxygen diffusion across the capillaries into skeletal muscle [61, 62].…”

“…While commonly measured at rest, a traditional paradigm in CF is that low FEV 1 and FVC are suggested to underpin depressed oxygen uptake () commensurate with exacerbated ventilation during cardiopulmonary exercise testing (CPET) [9–14]. However, in contrast to this pulmonary-centric model of CF, though it is understood that intrinsic CF and/or non-specific factors complicate the pathophysiologic understanding of the adolescent versus adult CF clinical phenotype (e.g., age of first presentation of CF [15] versus intrinsic aging effects on cardiovascular function and/or CPET approach [16–18], respectively), noteworthy observations across the CF age and disease severity spectrum suggest these individuals demonstrate signs of attenuated exercise capacity hypothesized to be reflective of an appreciable contribution of non-pulmonary factors (both cardiac and peripheral) [8, 12–14, 18–25]. …”

“…Although observations in adolescent or adult CF suggest in addition to impaired cardiac function [14, 22, 25, 32–34], these individuals may demonstrate abnormal peripheral function including skeletal muscle weakness or slowed muscle oxygenation kinetics [12, 18, 22, 23], which may cumulatively contribute to impaired aerobic exercise capacity coupled with ventilatory inefficiency, limited studies in adult CF have focused on describing the role of peripheral blood pressure [20, 35] in the context of questioning whether pulmonary dysfunction is accompanied by gross peripheral vascular abnormalities in these individuals [19, 21, 24, 36]. For example, whereas observations of Hull et al [20] (ergometry) or Schrage et al [35] (handgrip) do not suggest overt exacerbation of blood pressure during exercise in mild- to- moderate severity adult CF, it is both novel and relevant in understanding peripheral hemodynamic function in CF that Hull et al [20] demonstrated increased augmentation index in these individuals, suggesting the presence of increased arterial stiffness.…”