No abstract

We studied the dose-dependency of the lung pressure-volume curve (n -37) and morphometry (n -30) with intratracheally administered elastase. Four weeks after elastase was instilled at dosages of 20 (EL-20), 40, 80, and 100 U/100 g wt., chord compliance between 50 and 70% of total lung capacity (TLC) (C5o-70) and that between 80 and 100% TLC (C8o-100) Were measured. After a significant initial reduction, the weight of the EL-80 group recovered to the control level, whereas the weight curve of the EL-100 significantly decreased below that of the EL-80. Lung volumes of all the elastase-treated groups were significantly larger than those of control. Air-filled lung volumes monotonously increased when the elastase dose was increased from 20 to 80 U/100 g wt. In contrast lung volume of the EL-100 was significantly lower than that of the EL-80. On the other hand, liquid-filled lung volumes monotonously increased from 20 to 100 U/100 g wt. Cao-ioo was significantly smaller in the EL-100 than in the EL-80. The mean linear intercept increased and alveolar surface area decreased monotonously over the dose range tested. We conclude that there is a critical dose of elastase below which lung volume is increased and above which the increase is suppressed when elastase is administered intratracheally to Wistar rats. pulmonary emphysema ; mean linear intercept ; lung compliance ; alveolar surface area

P Pu ul lm mo on na ar ry y h ha ae em mo od dy yn na am mi ic cs s i in n a aw wa ak ke e r ra at ts s f fo ol ll lo ow wi in ng g t tr re ea at tm me en nt t w wi it th h e en nd do ot tr ra ac ch he ea al l p pa an nc cr re ea at ti ic c e el la as st ta as se e ABSTRACT: The purpose of this paper was to study pulmonary haemodynamics in an elastase-induced emphysema model in awake rats (Group-EL, n=9) in comparison with saline-treated controls (Group-C, n=12). Four weeks before haemodynamic study, porcine pancreatic elastase and normal saline were intratracheally instilled in Group-EL and Group-C, respectively. Indwelling pulmonary artery and abdominal aortic catheters were positioned two days before the haemodynamic study.Breathing room air, mean pulmonary artery pressure (Ppa) tended to be higher in Group-EL than in Group-C, although the difference was not statistically significant. Systemic pressure, total systemic vascular resistance and cardiac index did not differ between groups. When exposed to 10% O 2 , Ppa and pulmonary vascular resistance (PVR) of both groups rose significantly. The increase of Ppa, (but not PVR) in Group-EL during hypoxia was significantly higher than that in Group-C. The magnitude of hypoxic pulmonary vasoconstriction (HPV) tended to be larger in Group-EL than in Group-C. Right ventricles of Group-EL were more hypertrophic than those of Group-C, suggesting a period of higher pulmonary artery pressure than for Group-C.The present results imply that the pressor response of pulmonary vasculature to acute alveolar hypoxia is possibly enhanced in awake rats upon examination four weeks after elastase treatment. Eur Respir J., 1994Respir J., , 7, 1294Respir J., -1299

Whether or not theophylline inhibits hypoxic pulmonary vasoconstriction in vivo still remains uncertain. We therefore studied the effect of theophylline on hypoxic pulmonary vasoconstriction in awake rats. Two days before hemodynamic measurement, indwelling catheters were placed. Animals were divided into three groups; Group-H (20 mg/kg of theophylline), Group-L (8 mg/kg of theophylline), Group-S (saline). At the day of hemodynamic measurement, animals breathed 21% and 10% O2 gas. [{Pulmonary vascular resistance (PVR) during 10% O2-PVR during 21% O2}/PVR during 21% O2] x 100 was termed as hypoxic pulmonary vasoconstriction (HPV). The first HPV measurement was followed without drug administration and then the second HPV measurement was performed with theophylline or saline infusion. Post-theophylline HPV was divided by pre-theophylline HPV to normalize individual variation. Ratio of post-theophylline HPV to pre-theophylline HPV was 0.49 +/- 0.10, 0.77 +/- 0.23, 1.06 +/- 0.33 in Group -H, -L, -S, respectively (means +/- S.E.M). Ratio of post-theophylline HPV to pre-theophylline HPV was significantly less in Group-H than in Group-S. This result suggests that theophylline used in the present study (18.6-26.9 micrograms/ml) attenuates hypoxic pulmonary vasoconstriction in the unanesthetized rat.