Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema.
BACKGROUND
Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema.


METHODS
We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro.


RESULTS
In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 +/- 2.7 ms versus 53.9 +/- 2.4 ms). At both the RNA (RT-PCR) and protein (immunocytochemistry) levels, we found a significant decrease in the fastest, MHC isoform (IIb) in emphysema.


CONCLUSIONS
This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans.
Kim
Dong Kwan
DK
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Zhu
Jianliang
J
Kozyak
Benjamin W
BW
Burkman
James M
JM
Rubinstein
Neal A
NA
Lankford
Edward B
EB
Stedman
Hansell H
HH
Nguyen
Taitan
T
Levine
Sanford
S
Shrager
Joseph B
JB
D000222:Adaptation, Physiological; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003964:Diaphragm / Q000378:metabolism / Q000503:physiopathology*; D004646:Emphysema / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D008176:Lung Volume Measurements; D009119:Muscle Contraction; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D010196:Pancreatic Elastase; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D020033:Protein Isoforms; D012333:RNA, Messenger; D010196:Pancreatic Elastase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D000252:Calcium-Transporting ATPases