Impaired isotonic contractility and structural abnormalities in the diaphragm of congestive heart failure rats.
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 (P(t)) and maximal (P(o)) 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
P(t) and P(o) were respectively approximately 30% and approximately 20% lower in CHF diaphragm bundles than sham. Maximal shortening velocity was reduced by approximately 20% and maximal power generation by approximately 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.


CONCLUSIONS
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.
van Hees
Hieronymus W H
HW
Department of Pulmonary Diseases, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands.
van der Heijden
Henricus F M
HF
Hafmans
Theo
T
Ennen
Leo
L
Heunks
Leo M A
LM
Verheugt
Freek W A
FW
Dekhuijzen
P N Richard
PN
D000818:Animals; D003964:Diaphragm / Q000473:pathology* / Q000503:physiopathology*; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology*; D066298:In Vitro Techniques; D007551:Isotonic Contraction / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar