Impaired isotonic contractility and structural abnormalities in the diaphragm of congestive heart failure rats

Hieronymus W.H. van Hees, Henricus F.M. van der Heijden, Theo Hafmans, Leo Ennen, Leo M.A. Heunks, Freek W.A. Verheugt, P. N.Richard Dekhuijzen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Metabolic alterations and decreased isometric force generation have been demonstrated in different animal models for congestive heart failure (CHF). However, as few morphological examinations have been performed on the CHF diaphragm, it is unknown if structural abnormalities comprise a substrate for diaphragm dysfunction in CHF. Therefore, we investigated CHF diaphragm isometric and isotonic contractility together with the presence of structural abnormalities. Methods: Isometric twitch (Pt) and maximal (Po) force, shortening velocity and power generation were determined in diaphragm bundles from rats with CHF, induced by myocardial infarction, and sham-operated rats. Immunofluorescence staining of myosin and sarcolemmal components fibronectin, laminin and dystrophin was performed on diaphragm cryosections. Electron microscopy was used to study the ultrastructure of diaphragm fibres. Results: Pt and Po were respectively ∼ 30% and ∼ 20% lower in CHF diaphragm bundles than sham. Maximal shortening velocity was reduced by ∼ 20% and maximal power generation by ∼ 35%. Structural abnormalities were frequently observed in CHF diaphragm fibres and were mainly marked by focal degradation of sarcomeric constituents and expansion of intermyofibrillar spaces with swollen and degenerated mitochondria. Immunofluorescence microscopy showed reduced staining intensities of myosin in CHF diaphragm fibres compared to sham. No differences were found regarding the distribution of fibronectin, laminin and dystrophin, indicating an intact sarcolemma in both groups. Conclusion: This study demonstrates impaired isometric and isotonic contractility together with structural abnormalities in the CHF diaphragm. The sarcolemma of CHF diaphragm fibres appeared to be intact, excluding a role for sarcolemmal injuries in the development of CHF diaphragm dysfunction.

Original languageEnglish
Pages (from-to)326-335
Number of pages10
JournalInternational Journal of Cardiology
Volume128
Issue number3
DOIs
Publication statusPublished - 29 Aug 2008

Cite this

van Hees, H. W. H., van der Heijden, H. F. M., Hafmans, T., Ennen, L., Heunks, L. M. A., Verheugt, F. W. A., & Dekhuijzen, P. N. R. (2008). Impaired isotonic contractility and structural abnormalities in the diaphragm of congestive heart failure rats. International Journal of Cardiology, 128(3), 326-335. https://doi.org/10.1016/j.ijcard.2007.06.080