Source: Annual Congress 2010 - Respiratory and peripheral muscles: From basic mechanisms to altered function
Disease area: Airway diseases

Abstract

Introduction: In COPD patients, respiratory muscle dysfunction appears to be mainly the consequence of an abnormal thoracic configuration. However, molecular mechanisms such as oxidative stress and local cytokine production have also been proposed as contributors. The aim of the present study was to assess the role of local inflammatory phenomena in the diaphragm of rats exposed to daily bouts of increased respiratory loads. Methods: Wistar rats (n=16/group, ±300 g) were subjected to either high inspiratory threshold loads (±70% MIP) or placebo during 2h/d for 2 weeks. In addition, subgroups of animals received placebo vs. monoclonal therapy against TNF-α. The animals were placed in a plethysmographic chamber and inspiratory loads were applied through a threshold system. Diaphragms and leg muscles were excised at the end of the experimental period. Results: Damage and increases in the expression of different cytokines (TNF-α, IL-6, INF-γ) were observed in the diaphragm of loaded rats. In addition, there was an increase in the % of type I fibers. No changes were observed in the leg muscles. The use of therapy against TNF resulted in a higher level of muscle damage. Conclusions: Chronic exposure to high inspiratory loads induces damage in the diaphragm. This phenomenon is associated with elevated levels of expression of different cytokines. The increase in muscle damage resulting from the blockade of TNF suggests a key role of this cytokine in either preventing injury or in the repair process. Funded by: SAF2007-62719, CIBERES, FIS 04/1165 CP/040161 CM06/00204, SEPAR 06 & SOCAP 06.

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M. Domínguez-Alvarez, J. B. Gáldiz, F. Sánchez, F. J. Alvarez, J. Marín-Corral, C. Casadevall, J. Gea, E. Barreiro (Barcelona, Barakaldo, Spain). Inspiratory threshold loading: Effects on damage, inflammation and remodelling of the rat diaphragm. Eur Respir J 2010; 36: Suppl. 54, 3408

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