Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema

Dong Kwan Kim¹^,6, Jianliang Zhu¹, Benjamin W Kozyak¹, James M Burkman¹, Neal A Rubinstein², Edward B Lankford³, Hansell H Stedman¹^,2^,4, Taitan Nguyen⁵, Sanford Levine²^,5 and Joseph B Shrager¹^,2^,4

¹Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

²Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

³Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

⁴Department of Surgery, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA

⁵Department of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA

⁶Present address: Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

author email corresponding author email

Respiratory Research 2003, 4:1doi:10.1186/rr196


Published:	17 February 2003

Abstract

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.

Conclusion

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.