Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model.
BACKGROUND
Systemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease. We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease.


METHODS
Female NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control). Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration.


RESULTS
Mean linear intercept was higher in emphysema (260.7 +/- 26.8 microm) than in control lungs (24.7 +/- 1.7 microm). Emphysema mice lost body weight, controls gained weight. Running distance was shorter in emphysema than in controls. Diaphragm muscle length was shorter in controls compared to emphysema. Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms. Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls. Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length.


CONCLUSIONS
The elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation. The model may deepen our understanding of systemic aspects of COPD.
Lüthje
Lars
L
Kardiologie und Pneumologie, Georg-August-Universität, Göttingen, Germany. larsluethje@med.uni-goettingen.de
Raupach
Tobias
T
Michels
Hellmuth
H
Unsöld
Bernhard
B
Hasenfuss
Gerd
G
Kögler
Harald
H
Andreas
Stefan
S
D000818:Animals; D001835:Body Weight; D003964:Diaphragm / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D017079:Exercise Tolerance; D005260:Female; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008170:Lung Compliance; D051379:Mice; D018763:Muscle Fatigue; D009126:Muscle Relaxation; D009638:Norepinephrine / Q000652:urine; D010196:Pancreatic Elastase; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology* / Q000652:urine; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology* / Q000652:urine; D012720:Severity of Illness Index; D013552:Swine; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology
D010196:Pancreatic Elastase; D009638:Norepinephrine