(267) Skeletal Muscle Oxygenation Extraction Is Lower In Women Compared To Men With Cystic Fibrosis

Background: Women with cystic fibrosis (CF) have a steeper decline in pulmonary function and a greater prevalence of CF-related diabetes (CFRD) compared with men with CF, creating a gender gap in disease progression. Exercise capacity, an independent predictor of mortality in CF, is reduced in women compared to men with CF. In fact, reduced skeletal muscle oxygen (O₂) extraction and utilization during exercise contributes to lower exercise capacity in CF. Our lab has also observed that glycosylated hemoglobin can impair tissue oxygenation and extraction during exercise in CF. The purpose of the present investigation was to test if women with CF have lower O₂ extraction and utilization during maximal exercise compared to men with CF.

Methods: 10 women (age=26±10; mean ppFEV₁=82±30%; mean body mass index=23.4±3.8 kg/m­²) and 10 men (age=22±9; mean ppFEV₁=89±18%; mean body mass index=22.6±3.3 kg/m­²) with CF were recruited to participate in this study. Each participant completed an oral glucose tolerance test (OGTT) and a maximal exercise test following the Godfrey protocol on a cycle ergometer to determine VO₂ peak (ml/kg/min). Near-Infrared Spectroscopy (NIRS) was placed on the right vastus lateralis to measure oxygenated (O₂Hb), deoxygenated (HHb), and total (tHb) myoglobin/hemoglobin during exercise. NIRS data were normalized using a 2-minute baseline period where the leg was placed in a stationary position. The change in tHb was calculated by subtracting the baseline tHb from the tHb at VO₂peak. Area under the curve was calculated for each participant’s OGTT.

Results: VO₂ peak was lower in women compared to men with CF (M: 27.9±6.6 vs W: 23.1±4.6 ml/kg/min; p=0.078) and this difference remained when controlling for OGTT area under the curve (p=0.098). At rest, no differences in muscle blood volume were identified between men and women with CF (M: 1.83±3.33 vs W: 2.54±2.74 uM; p=0.611). However, tHb was significantly (p≤0.035) lower in women compared to men with CF when exercise intensity was 50% of VO₂peak or greater. Similarly, O₂Hb was not different at rest (M: 2.17±4.12 vs W: 21.23±2.02 uM; p=0.525) and tended to be lower in women at exercise intensities greater than 60% (p≤0.117). Baseline HHb concentrations were different between men and women with CF (M: -0.34±1.92 vs W: 1.31±1.48 uM; p=0.023). As exercise intensity increased over 60% VO₂peak, HHb significantly decreased in women whereas it was increased in men (p≤0.031). The change in blood flow during exercise was negatively associated with the OGTT area under the curve in women with CF only (M: r=0.551, p=0.124 vs W: r=-0.482, p=0.189).

Conclusions: Muscle blood flow during exercise is lower in women compared to men with CF, contributing to the observed differences in O₂ extraction and utilization. The change in blood flow was negatively associated with glucose regulation in women, but not men with CF. Impaired glucose regulation in women with CF may contribute to reductions in blood flow during exercise and subsequent O₂ extraction inefficiency and exercise intolerance.

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