Journal of applied physiology
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Clinical Trial Controlled Clinical Trial
Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression in human diaphragm.
We have previously demonstrated that human diaphragm remodeling elicited by severe chronic obstructive pulmonary disease (COPD) is characterized by a fast-to-slow myosin heavy chain isoform transformation. To test the hypothesis that COPD-induced diaphragm remodeling also elicits a fast-to-slow isoform shift in the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), the other major ATPase in skeletal muscle, we obtained intraoperative biopsies of the costal diaphragm from 10 severe COPD patients and 10 control subjects. We then used isoform-specific monoclonal antibodies to characterize diaphragm fibers with respect to the expression of SERCA isoforms. ⋯ The combination of these histological and immunoblot results is consistent with the hypothesis that diaphragm remodeling elicited by severe COPD is characterized by a fast-to-slow SERCA isoform transformation. Moreover, the combination of these SERCA data and our previously reported myosin heavy chain isoform data (Levine S, Nguyen T, Kaiser LR, Rubinstein NA, Maislin G, Gregory C, Rome LC, Dudley GA, Sieck GC, and Shrager JB. Am J Respir Crit Care Med 168: 706-713, 2003) suggests that diaphragm remodeling elicited by severe COPD should decrease ATP utilization by the diaphragm.
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Athletes with spinal cord injury (SCI), and in particular tetraplegia, have an increased risk of heat strain and consequently heat illness relative to able-bodied individuals. Strategies that reduce the heat strain during exercise in a hot environment may reduce the risk of heat illness. To test the hypotheses that precooling or cooling during intermittent sprint exercise in a heated environment would attenuate the rise in core temperature in tetraplegic athletes, eight male subjects with SCI (lesions C(5)-C(7); 2 incomplete lesions) undertook four heat stress trials (32.0 +/- 0.1 degrees C, 50 +/- 0.1% relative humidity). ⋯ Moreover, perceived exertion was lower during Pre (13 +/- 2; P < 0.01) and Dur (12 +/- 1; P < 0.01) compared with Con (14 +/- 2). These results suggest that both precooling and cooling during intermittent sprint exercise in the heat reduces thermal strain in tetraplegic athletes. The cooling strategies also appear to show reduced perceived exertion at equivalent time points, which may translate into improved functional capacity.
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Comparative Study
Neutrophil inhibition with L-selectin-directed MAb improves or worsens survival dependent on the route but not severity of infection in a rat sepsis model.
Both route and severity of infection may influence immunomodulator agents in sepsis. We studied the effect of each variable on HRL-3, an L-selectin-directed MAb that inhibits neutrophil function, in a rat sepsis model. Animals (n = 800) were randomized to be treated with either HRL-3 or placebo and to receive Escherichia coli either intravenously (IV) or intrabronchially (IB) in doses producing low or high mortality rates. ⋯ In contrast, with IB E. coli HRL-3 reduced the hazards ratio early (-1.1 +/- 0.36) but worsened it late (0.87 +/- 0.23) (P = 0.002 for both effects over all E. coli doses) in patterns significantly different from IV E. coli (P < 0.0001). Compared with control, although HRL-3 did not alter lung neutrophil numbers or injury score at 6 or 168 h with IV E. coli (P = ns for all), it reduced both early and increased them late with IB E. coli (P