Figure 6.
Figure 6. PDP reduced thrombin-related lung edema formation in mice lungs. Isolated mice lungs were perfused and ventilated for 45 minutes before administration of 750 μM thrombin within one minute. After a further 30 minutes, the experiment was terminated and lungs were used to measure wet-dry weight ratio (W/D) (A) or lung permeability for albumin (B). PDE inhibitors were added to the lung perfusate 10 minutes prior to thrombin stimulation. PDE4 inhibitor piclamilast and PDE2 inhibitor PDP were used at a concentration of 1 μM. Lung W/D is the ratio between the weight at the end of the experiment and the weight after drying of the lungs (A). PDE2 (PDP) inhibition reduced lung W/D, while PDE4 inhibition (piclamilast) did not show a significant reduction of lung edema formation. Albumin flux to the bronchoalveolar compartment was measured by admixing human serum albumin (HSA) to the perfusate at a concentration of 0.04% 20 minutes prior to thrombin stimulation and subsequent measurement of the HSA concentration in the bronchoalveolar lavage fluid after termination of the experiment (B). PDE2 (PDP) inhibition and PDE4 inhibition (piclamilast) reduced permeability for albumin. Data presented are mean ± SEM of 5 independent experiments. *P < .05.

PDP reduced thrombin-related lung edema formation in mice lungs. Isolated mice lungs were perfused and ventilated for 45 minutes before administration of 750 μM thrombin within one minute. After a further 30 minutes, the experiment was terminated and lungs were used to measure wet-dry weight ratio (W/D) (A) or lung permeability for albumin (B). PDE inhibitors were added to the lung perfusate 10 minutes prior to thrombin stimulation. PDE4 inhibitor piclamilast and PDE2 inhibitor PDP were used at a concentration of 1 μM. Lung W/D is the ratio between the weight at the end of the experiment and the weight after drying of the lungs (A). PDE2 (PDP) inhibition reduced lung W/D, while PDE4 inhibition (piclamilast) did not show a significant reduction of lung edema formation. Albumin flux to the bronchoalveolar compartment was measured by admixing human serum albumin (HSA) to the perfusate at a concentration of 0.04% 20 minutes prior to thrombin stimulation and subsequent measurement of the HSA concentration in the bronchoalveolar lavage fluid after termination of the experiment (B). PDE2 (PDP) inhibition and PDE4 inhibition (piclamilast) reduced permeability for albumin. Data presented are mean ± SEM of 5 independent experiments. *P < .05.

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