Background: Patients with congestive heart failure (CHF) experience reduced skeletal muscle exercise tolerance. The mechanism underlying this is not known. Studies have indicated that the extracellular matrix (ECM) may be affected by the CHF condition. The signal from the failing heart that trigger such changes has not been defined, and it is not known to which extent the skeletal muscle itself contributes by sustaining and amplifying a local process. Hence, we have examined various components of skeletal muscle ECM and interstitial fluid (IF) during development of CHF.

Methods: We used a post infarction model of CHF in rats. Cytokines in plasma and IF were analysed by multiplex technique, while matrixmetalloproteinase (MMP) activity and collagen content in muscle samples were determined with a gelatinase assay and colorimetric assay of hydroxyproline, respectively.

Results: Of the analysed cytokines, vascular endothelial growth factor (VEGF) in IF was significantly lower in CHF compared to Sham. In addition, VEGF was higher in IF compared to plasma, indicating a net VEGF production in the muscle. Also IL18 was higher in IF compared to plasma, but no apparent changes were detected between CHF and Sham. Both the MMP-activity and the collagen content were higher in muscles from CHF compared to Sham.

Conclusions: The reduced exercise tolerance in CHF may be due to MMP-induced alterations in extracellular matrix. A reduced production of VEGF in muscles from the CHF animals may have implications for the development of exercise intolerance in these animals by limiting their capillary exchange area.