Ex Vivo Pulmonary Oedema after In Vivo Blast-Induced Rat Lung Injury: Time Dependency, Blast Intensity and Beta-2 Adrenergic Receptor Role

Biomedicines. 2022 Nov 15;10(11):2930. doi: 10.3390/biomedicines10112930.


Objective: Current treatments for blast-induced lung injury are limited to supportive procedures including mechanical ventilation. The study aimed to investigate the role of post-trauma-induced oedema generation in the function of time and trauma intensity and the probable role of beta 2-adrenergic receptors (β2-ARs) agonists on pulmonary oedema. The study is conducted using an ex vivo model after an experimental in vivo blast-induced thorax trauma in rats. Methods: Rats were randomised and divided into two groups, blast and sham. The blast group were anaesthetised and exposed to the blast wave (3.16 ± 0.43 bar) at a distance of 3.5 cm from the thorax level. The rats were sacrificed 10 min after the blast, the lungs explanted and treated with terbutaline, formoterol, propranolol or amiloride to assess the involvement of sodium transport. Other groups of rats were exposed to distances of 5 and 7 cm from the thorax to reduce the intensity of the injury. Further, one group of rats was studied after 180 min and one after 360 min after a 3.5 cm blast injury. Sham controls were exposed to identical procedures except for receiving blast overpressure. Results: Lung injury and oedema generation depended on time after injury and injury intensity. Perfusion with amiloride resulted in a further increase in oedema formation as indicated by weight gain (p < 0.001), diminished tidal volume (Tv) (p < 0.001), and increased airway resistance (p < 0.001). Formoterol caused a significant increase in the Tv (p < 0.001) and a significant decrease in the airway resistance (p < 0.01), while the lung weight was not influenced. Trauma-related oedema was significantly reduced by terbutaline in terms of lung weight gain (p < 0.01), Tv (p < 0.001), and airway resistance (p < 0.01) compared to control blast-injured lungs. Terbutaline-induced effects were completely blocked by the β-receptor antagonist propranolol (p < 0.05). Similarly, amiloride, which was added to terbutaline perfusion, reversed terbutaline-induced weight gain reduction (p < 0.05). Conclusions: β2-adrenoceptor stimulation had a beneficial impact by amiloride-dependent sodium and therefore, fluid transport mechanisms on the short-term ex vivo oedema generation in a trauma-induced in vivo lung injury of rats.

Keywords: amiloride; blast lung injury; formoterol; inflammation; pulmonary oedema; sodium transport; terbutaline; β2-adrenoceptor agonist.

Grants and funding

The work of Y.H., U.M. and J.H. have been funded by Lungen- und Atmungsstiftung Bern, Switzerland which provides non-restricted financial support toward research on lung, respiratory and sleep-related respiratory diseases as well as related rehabilitation and lifestyle change issues such as exercise, smoking cessation, etc. J.H. is the chair of Lungen- und Atmungsstiftung Bern and his position did not influence the design of the study, the collection of the data, the analysis or interpretation of the data, the decision to submit the manuscript for publication, or the writing of the manuscript and did not present any financial conflicts. Also, the work of J.H. was supported by a grant from the Deutsche Forschungsgemeinschaft (FOR 321/2-1; research group “Endogenous tissue injury: Mechanisms of autodestruction”) and by the Herrmann Josef Schieffer Prize of the “Freunde des Universitätsklinikums Homburg e.V.”. All remaining authors (H.H., L.B., U.S., F.G., A.W. and R.L.) declare no potential financial or non-financial conflict of interest with the work presented here.