Submitted on July 21, 2008
Revised on March 30, 2009
Accepted on March 30, 2009
Temporary fatigue and altered extracellular matrix in skeletal muscle during progression of heart failure in rats
Tommy Aune Rehn1*, Bengt Åge Sørby Borge2, Per Kristian Lunde1, Morten Munkvik3, Marianne Lunde Sneve1, Frøy Grøndahl1, Jan Magnus Aronsen3, Ivar Sjaastad4, Kristian Prydz1, Svein Olav Kolset1, Helge Wiig2, Ole M. Sejersted1, and Per Ole Iversen5
1 University of Oslo
2 University of Bergen
3 Ullevål University Hospital
4 Ullevaal University Hospital
5 Inst. of Basic Medical Sciences, University of Oslo
* To whom correspondence should be addressed. E-mail: tommyrehn{at}yahoo.no.
Patients with congestive heart failure (CHF) experience increased skeletal muscle fatigue. The mechanism underlying this phenomenon is unknown, but a deranged extracellular matrix (ECM) might be a contributing factor. Hence we examined ECM components and regulators in a rat post-infarction model of CHF. At various time points during a 3.5 month-period after induction of CHF in rats by left coronary artery ligation, blood, interstitial fluid (IF) and muscles were sampled. Isofluran anesthesia was employed during all surgical procedures. IF was extracted by wicks inserted intermuscularly in a hind limb. We measured cytokines in plasma and IF whereas MMP activity and collagen content as well as the level of glycosaminoglycans and hyaluronan were determined in hind limb muscle. In vivo fatigue protocols of the soleus muscle were performed at 42 and 112 days after induction of heart failure. We found that the MMP activity and collagen content in the skeletal muscles increased significantly at 42 days after induction of CHF, and these changes were time-related to increased skeletal muscle fatigability. These parameters returned to Sham levels at 112 days. Vascular endothelial growth factor (VEGF) in IF was significantly lower in CHF compared to Sham-operated rats at 3 and 10 days, but no difference was observed at 112 days. We conclude that temporary alterations in the ECM, possibly triggered by VEGF, are related to a transient development of skeletal muscle fatigue in CHF.
