Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats.

BACKGROUND: Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism. METHODS: Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography. RESULTS: In the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting. CONCLUSIONS: Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

Comparison of the respiratory effects of commonly utilized general anaesthesia regimes in male Sprague-Dawley rats.

Background: Respiratory parameters in experimental animals are often characterised under general anaesthesia. However, anaesthesia regimes may alter the functional and mechanical properties of the respiratory system. While most anaesthesia regimes have been shown to affect the respiratory system, the effects of general anaesthesia protocols commonly used in animal models on lung function have not been systematically compared. Methods: The present study comprised 40 male Sprague-Dawley rats divided into five groups (N = 8 in each) according to anaesthesia regime applied: intravenous (iv) Na-pentobarbital, intraperitoneal (ip) ketamine-xylazine, iv propofol-fentanyl, inhaled sevoflurane, and ip urethane. All drugs were administered at commonly used doses. End-expiratory lung volume (EELV), airway resistance (Raw) and tissue mechanics were measured in addition to arterial blood gas parameters during mechanical ventilation while maintaining positive end-expiratory pressure (PEEP) values of 0, 3, and 6 cm H2O. Respiratory mechanics were also measured during iv methacholine (MCh) challenges to assess bronchial responsiveness. Results: While PEEP influenced baseline respiratory mechanics, EELV and blood gas parameters (p < 0.001), no between-group differences were observed (p > 0.10). Conversely, significantly lower doses of MCh were required to achieve the same elevation in Raw under ketamine-xylazine anaesthesia compared to the other groups. Conclusion: In the most frequent rodent model of respiratory disorders, no differences in baseline respiratory mechanics or function were observed between commonly used anaesthesia regimes. Bronchial hyperresponsiveness in response to ketamine-xylazine anaesthesia should be considered when designing experiments using this regime. The findings of the present study indicate commonly used anaesthetic regimes allow fair comparison of respiratory mechanics in experimental animals undergoing any of the examined anaesthesia protocols.

Lung and chest wall mechanical properties in metformin-treated and untreated models of type 2 diabetes.

The adverse respiratory consequences of type 2 diabetes mellitus (T2DM) may reflect compromised lung function and/or alterations of the chest wall because of skeletal muscle stiffening. We assessed the separate contributions of these compartments to respiratory complications in diabetes and explored the effects of metformin on respiratory abnormalities. Experiments were performed in untreated rats (control, n = 7), high-fat diet-fed rats receiving streptozotocin (T2DM, n = 7), and metformin-treated diabetic rats (MET, n = 6). Newtonian resistance, tissue damping, and elastance were separately assessed for lung and chest wall components by measuring the esophageal pressure during forced oscillations at low (0 cmH2O), medium (3 cmH2O), and high positive end-expiratory pressure (PEEP) (6 cmH2O). Tissue hysteresivity was calculated as damping/elastance. Blood gas parameters were used to assess gas exchange, and lung histology was performed to characterize collagen expression. T2DM at low PEEP compromised airway and lung tissue mechanics in association with gas-exchange defects and collagen overexpression. Abnormal chest wall mechanics in T2DM was indicated only by decreased tissue hysteresivity. No difference in lung or chest wall mechanics, gas exchange, or lung histology was observed between the MET and control groups. These findings suggest the primary involvement of the pulmonary system in the respiratory consequences of T2DM, with chest wall properties only disturbed by a shift toward the dominance of elastic forces at low PEEP. The adequacy of metformin to treat the adverse respiratory consequences of diabetes was also revealed, in addition to its well-established beneficial effects on other organs.NEW & NOTEWORTHY The present study examined the contributions of the lungs and chest wall to respiratory complications in a rat model of diabetes and clarified the effects of metformin on these changes. At low positive end-expiratory pressure, type 2 diabetes was linked to dysfunctional airway and lung tissue mechanics in relation with gas-exchange defects and collagen overexpression, whereas decreased tissue hysteresivity was manifested in the chest wall abnormalities. Metformin treated all adverse respiratory consequences of diabetes.