Noradrenalin effectively rescues mice from blast lung injury caused by laser-induced shock waves

Abstract

Background: Blast lung injuries (BLI) caused by blast waves are extremely critical in the prehospital setting, and hypotension is thought to be the main cause of death in such cases. The present study aimed to elucidate the pathophysiology of severe BLI using laser-induced shock wave (LISW) and identify the initial treatment. Methods: The current investigation comprised two parts. For the validation study, mice were randomly allocated to groups that received a single shot of 1.2, 1.3, or 1.4 J/cm2 LISW to both lungs. The survival rates, systolic blood pressure (sBP), heart rate (HR), peripheral oxyhemoglobin saturation (SpO2), and shock index were monitored for 60 min, and lung tissues were analyzed histopathologically. The study evaluated the effects of catecholamines as follows. Randomly assigned mice received 1.4 J/cm2 LISW followed by the immediate intraperitoneal administration of dobutamine, noradrenalin, or normal saline. The primary outcome was the survival rate. Additionally, sBP, HR, SpO2, and the shock index were measured before and 5 and 10 min after LISW, and the cardiac output, left ventricular ejection fraction, and systemic vascular resistance (SVR) were determined before and 1 min after LISW. Results: The triad of BLI (hypotension, bradycardia, and hypoxemia) was evident immediately after LISW. The survival rates worsened with increasing doses of LISW (100 % in 1.2 J/cm2 vs. 60 % in 1.3 J/cm2, 10 % in 1.4 J/cm2). The histopathological findings were compatible with those of human BLI. The survival rate in LISW high group (1.4 J/cm2) was highest in the group that received noradrenalin (100 %), with significantly elevated SVR values (from 565 to 1451 dyn s/min5). In contrast, the survival rates in the dobutamine and normal saline groups were 40 and 10 %, respectively, and the SVR values did not change significantly after LISW in either group. Conclusions: The main cause of death during the initial phase of severe BLI is hypotension due to the absence of peripheral vasoconstriction. Therefore, the immediate administration of noradrenalin may be an effective treatment during the initial phase of severe BLI.