RESUMO
BACKGROUND: The cardiopulmonary exercise test (CPET) is the gold standard for assessing aerobic fitness; however, it is expensive, not widely available, and requires specialized equipment and staff. The incremental shuttle walking test (ISWT) is an exercise field test used to evaluate exercise capacity and may be an alternative to CPET in patients with lymphangioleiomyomatosis (LAM). OBJECTIVE: To investigate whether the ISWT can be used to assess maximal aerobic capacity in patients with LAM. METHODS: Forty-five women were evaluated on two days, and they randomly performed the CPET and ISWT. The maximum oxygen uptake (peak VO2) was evaluated using gas analyzers in both tests. The carbon dioxide production (VCO2), respiratory exchange ratio (RER), and heart rate (HR) were compared during peak exercise. Pearson's correlation and Bland-Altman assessed the association and agreement, respectively. The intraclass correlation coefficient (ICC) was used to assess the reliability of the data. RESULTS: All patients (46.1 ± 10.2 years) presented similar peak VO2, RER, and peak HR during the CPET and ISWT (15.6 ± 4.6 vs. 15.7 ± 4.4 ml·kg-1·min-1; 1.15±0.09 vs. 1.17±0.12; and 142.2 ± 18.6 vs. 141.5 ± 22.2 bpm, respectively; p>0.05). A good linear correlation (r = 0.79; p<0.001) and ICC (0.86; 95%CI 0.74-0.93) were observed between the peak VO2 in both tests. Predictive peak VO2 equations based on the ISWT performance are also presented. CONCLUSION: Our results suggest that the ISWT can be used to assess maximal exercise performance in patients with LAM, and it is a valuable option to be used as an alternative to the CPET and predict maximal exercise capacity.
RESUMO
BACKGROUND AND PURPOSE: The two longest C-termini of the purinergic P2X receptors occur in the P2X2 and P2X7 receptors and are thought to interact with multiple cytoplasmic proteins, among which are members of the cytoskeleton, including microtubules. In this work we asked whether disrupting the microtubule cytoskeleton might affect the functions of these receptors. EXPERIMENTAL APPROACH: Functions of heterologously expressed P2X2 and P2X7 receptors were evaluated with electrophysiology and dye uptake following ATP application. Permeabilization and secretion of pro-inflammatory agents were quantified from fresh or cultured peritoneal mouse macrophages, treated in vitro or in vivo with colchicine. KEY RESULTS: Disrupting the microtubule network with colchicine did not affect currents generated by ATP in P2X2 and P2X7 receptor-expressing cells but inhibited uptake of the dye Yo-Pro-1 in Xenopus oocytes and HEK293 cells expressing these channels. Peritoneal mouse macrophages showed less ATP-induced permeabilization to ethidium bromide in the presence of colchicine, and less reactive oxygen species (ROS) formation, nitric oxide (NO) and interleukin (IL)-1ß release. Colchicine treatment did not affect ATP-evoked currents in macrophages. Finally, in vivo assays with mice inoculated with lipopolysaccharide and ATP showed diminished ROS, IL-1ß, interferon-γ and NO production after colchicine treatment. CONCLUSIONS AND IMPLICATIONS: Colchicine has known anti-inflammatory actions and is used to treat several conditions involving innate immunity, including gout and familial Mediterranean fever. Here we propose a new mechanism of action - inhibition of pore formation induced by activation of P2X receptors - which could explain some of the anti-inflammatory effects of colchicine.
