, 2007). This area of the brain is strongly implicated in respiratory sensations ( Morelot-Panzini et al., 2007). It follows that C-fiber stimulation during loading – particularly the C-fibers originating in the rib-cage muscles ( Ward et al., 1988; Chiti et al., 2008; Similowski et al., 2000) – could have been causally linked to the intolerable discomfort during loading and at task failure. Over the course of loading, VT decreased, and reached its nadir at task failure ( Fig. 3). This observation raises the possibility that

a decreased afferent discharge originating in the pulmonary stretch receptors could have contributed to the intolerable discomfort to breathe at task failure. This possibility LY2835219 datasheet is supported by the observation that most subjects commented that the IC maneuvers performed during loading and at task failure provided an immediate, albeit temporary, decrease ABT-888 cell line in respiratory discomfort. This finding is analogous to the relief of dyspnea that accompanies the first breath after breath holding ( Flume et al., 1994). Moreover, it sheds light on the observations

of Banzett et al. (1996) and Gorman et al. (1999), who reported that progressively greater mechanical constraint on inhalation augments the sensation of air hunger. Improvement in diaphragmatic coupling during loading was equivalent in fatiguers and non-fatiguers. Duration of loading, ΔEAdi at task failure, and TTdi were also similar in the two groups (Fig. 8). What distinguished non-fatiguers from fatiguers were a slower respiratory frequency and a longer TE ( Fig. 9). TI was similar in the two groups (data not shown). We speculate that the differences

in breathing pattern were mechanistically linked to development of contractile fatigue. Specifically, relaxation time (TE) and, thus, unhindered perfusion time [with possible post-contraction hyperemia ( Bellemare and Bigland-Ritchie, 1987)] were longer in the non-fatiguers than in the fatiguers. That is, greater diaphragmatic perfusion Enzalutamide ic50 in the non-fatiguers satisfied the metabolic demands of the contracting muscle. This, in turn, could have protected the diaphragm from developing contractile fatigue ( Bellemare and Bigland-Ritchie, 1987). Consequent to curtailment of TE, respiratory frequency was faster in the fatiguers than in the non-fatiguers ( Fig. 9). This finding raises two considerations. First, tachypnea could have promoted fatigue. PETCO2, however, was lower at task failure in the fatiguers than in the non-fatiguers. Accordingly, either the breathing pattern of the fatiguers was effective at alleviating hypercapnia or the development of fatigue caused earlier onset of task failure. That the duration of loading was not significantly different between fatiguers and non-fatiguers supports the former rather than the latter possibility.