Larry C Lands | PubMed Health

PubMed2002

Role of heme oxygenases in sepsis-induced diaphragmatic contractile dysfunction and oxidative stress.

Heme oxygenases (HOs), essential enzymes for heme metabolism, play an important role in the defense against oxidative stress. In this study, we evaluated the expression and functional significance of HO-1 and HO-2 in the ventilatory muscles of normal rats and rats injected with bacterial lipopolysaccharide (LPS). Both HO-1 and HO-2 proteins were detected inside ventilatory and limb muscle fibers of normal rats. Diaphragmatic HO-1 and HO-2 expressions rose significantly within 1 and 12 h of LPS injection, respectively. Inhibition of the activity of inducible nitric oxide synthase (iNOS) in rats and absence of this isoform in iNOS(-/-) mice did alter sepsis-induced regulation of muscle HOs. Systemic inhibition of HO activity with chromium mesoporphyrin IX enhanced muscle protein oxidation and hydroxynonenal formation in both normal and septic rats. Moreover, in vitro diaphragmatic force generation declined substantially in response to HO inhibition both in normal and septic rats. We conclude that both HO-1 and HO-2 proteins play an important role in the regulation of muscle contractility and in the defense against sepsis-induced oxidative stress.

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PubMed2002

Isokinetic muscle function in COPD.

AIM: Exercise limitation in patients with COPD has been attributed to impaired ventilation and reduced skeletal muscle function. We have previously used a combination of FEV(1) and leg muscle function (work achieved during a 30-s isokinetic sprint test) to predict progressive exercise capacity. However, the 30-s test may not be well tolerated in patients with advanced lung disease. We studied the relationship between progressive exercise capacity, FEV(1), and isokinetic work in patients with COPD and in healthy control subjects to assess whether the work accomplished at time intervals of < 30 s could also be used to predict progressive maximal exercise capacity (Wmax). METHODS: Twenty-seven patients with COPD and 29 control subjects underwent anthropometric measures, spirometry, progressive cycle ergometry, and 30-s isokinetic cycling. RESULTS: There was no significant difference for weight, height, or body mass index between the groups. The COPD group was slightly older and had a significantly lower FEV(1) than control subjects. They also had a lower Wmax (56 +/- 28.3 W vs 141.9 +/- 46.7 W) and isokinetic work accomplished over 10 s (W10), over 15 s (W15), over 20 s (W20), over 25 s (W25), and over 30 s (W30). Wmax correlated in both patients with COPD and in control subjects with W10, W15, W20, W25, W30, and FEV(1). Combining FEV(1) and isokinetic work (W10, W15, W20, W25, or W30) in a two-factor model to predict Wmax, the coefficients of determination (r(2)) for patients with COPD were 0.57, 0.57, 0.58, 0.59, and 0.58, and for control subjects were 0.69, 0.69, 0.71, 0.71, and 0.73, respectively. Wmax correlated with weight only in control subjects. CONCLUSIONS: Both ventilatory function and leg muscle function contribute to exercise limitation, and a 20-s isokinetic test can be utilized to assess leg function in patients with COPD.

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