title: Lung volume reduction surgery restores the normal diaphragmatic length-tension relationship in emphysematous rats.
abstract: OBJECTIVE
  Improved respiratory muscle function is a major effect of a lung volume reduction surgery. We studied length adaptation in rat diaphragmatic muscle in an attempt to elucidate the mechanism by which diaphragmatic function improves after this controversial operation.
  
  
  METHODS
  We developed a model of elastase-induced emphysema and bilateral volume reduction through median sternotomy in rats. Five months after emphysema induction, maximum exchangeable lung volume was determined in intubated and anesthetized control animals and animals with emphysema. Costal diaphragmatic length was measured in vivo, and the length at which maximal twitch force is generated was determined on muscle strips in vitro. Also 5 months after elastase administration, another cohort underwent volume reduction or sham sternotomy. Five months after the operation, these animals were similarly studied.
  
  
  RESULTS
  Lung volume was increased in emphysematous rats versus control rats (50.9 +/- 1.7 vs 45.4 +/- 1.3 mL, P =.001). Lung volume was decreased in emphysematous animals that had undergone volume reduction versus sham sternotomy (44.7 +/- 0.60 vs 49.4 +/- 1.0 mL, P =.001). In situ diaphragm length (1.99 +/- 0.04 vs 2.24 +/- 0.07 cm, P =.001) and the length at which maximal twitch force is generated (2.25 +/- 0.06 vs 2.48 +/- 0.09 cm, P =.038) were shorter in emphysematous than control animals. After volume reduction, in situ diaphragm length (2.13 +/- 0.06 vs 1.83 +/- 0.02 cm, P <.001) and the length at which maximal twitch force is generated (2.50 +/- 0.08 vs 2.27 +/- 0.06 cm, P =.013) were longer than in animals undergoing sham sternotomy.
  
  
  CONCLUSIONS
  In this experimental model of emphysema and lung volume reduction surgery, emphysema shortens the length at which maximal twitch force is generated and shifts the diaphragmatic length-tension curve to lower lengths; volume reduction returns the length at which maximal twitch force is generated toward normal and shifts the diaphragmatic length-tension curve back to longer lengths. This restoration toward normal physiology may enable the improvement in diaphragmatic function seen after lung volume reduction surgery. The mechanism by which these length adaptations occur merits further investigation.
authors.affiliation: Section of General Thoracic Surgery, Department of Surgery, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA. jshrag@mail.med.upenn.edu
authors.forename: J B
authors.initials: JB
authors.lastname: Shrager
authors.forename: D K
authors.initials: DK
authors.lastname: Kim
authors.forename: Y J
authors.initials: YJ
authors.lastname: Hashmi
authors.forename: E B
authors.initials: EB
authors.lastname: Lankford
authors.forename: P
authors.initials: P
authors.lastname: Wahl
authors.forename: H H
authors.initials: HH
authors.lastname: Stedman
authors.forename: S
authors.initials: S
authors.lastname: Levine
authors.forename: L R
authors.initials: LR
authors.lastname: Kaiser
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D003964:Diaphragm / Q000502:physiology*; D008168:Lung / Q000502:physiology / Q000601:surgery; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D011656:Pulmonary Emphysema / Q000503:physiopathology* / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors