Journal
INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 141, Issue 3, Pages 275-283Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2008.12.042
Keywords
Heart failure; Diaphragm; Passive tension; Titin
Categories
Funding
- NIH [HL06288]
Ask authors/readers for more resources
Background: Diaphragm dysfunction is well-known to limit quality of life and prognosis of patients with heart failure (HF), but its underlying mechanisms are not well understood. In an animal model for HF we recently showed that impaired diaphragm contractility arises at the single fiber level and is associated with sarcomeric injuries. For optimal muscle function and sarcomeric stability passive elastic structures, like titin, are indispensable. The current study aimed to investigate if impaired passive elasticity contributes to diaphragm dysfunction in rats with heart failure. Methods: Skinned muscle fibers were isolated from the diaphragm and soleus of rats with chronic HF, induced by left coronary artery ligation and of sham-operated rats. Passive tension-length relationships were determined by applying segmental extension tests. Immunofluorescence was performed on muscle cryosections using antibodies (T12) against a titin epitope near the Z-line. Titin content was determined by SDS-agarosegel electrophoresis. Titin's mobility on gel was studied to detect changes in titin size. Results: Passive tension generation upon stretch was significantly reduced (>35%) in HF diaphragm fibers compared to sham. Immunostaining intensities against titin were reduced in diaphragm cryosections of HF rats compared to sham. Soleus fibers from HF and sham rats did not display differences, neither in passive tension nor in immunostaining. No differences in titin's size were detected in HF and sham diaphragm. Titin content, however, was significantly reduced (similar to 25%) in HF diaphragm. Discussion: We conclude that in the diaphragm of HF rats, passive elasticity is impaired, mainly resulting from titin loss. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available