Examining lethality risk for rodent studies of primary blast lung injury

Abstract

While protective measures have been taken to mitigate injury to the thorax during a blast exposure, primary blast lung injury (PBLI) is still evident in mounted/in vehicle cases during military conflicts. Moreover, civilians, who are unprotected from blast exposure, can be severely harmed by terrorist attacks that use improvised explosive devices (IEDs). Since the lungs are the most susceptible organ due to their air-filled nature, PBLI is one of the most serious injuries seen in civilian blast cases. Determining lethality threshold for rodent studies is crucial to guide experimental designs centered on therapies for survival after PBLI or mechanistic understanding of the injury itself. Using an Advanced Blast Simulator, unprotected rats were exposed to a whole body blast to induce PBLI. The one-hour survival rate was assessed to determine operating conditions for a 50% lethality rate. Macroscopic and histological analysis of lung was conducted using hematoxylin and eosin staining. Results demonstrated lethality risk trends based on static blast overpressure (BOP) for rodent models, which may help standardized animal studies and contribute to scaling to the human level. The need for a standardized method of producing PBLI is pressing and establishing standard curves, such as a lethality risk curve for lung blasts, is crucial for this condensing of BOP methods.

Figure 1

ABS at Virginia Tech with a representative figure used for peak overpressure calculation.

Figure 2

Macroscopic images of lungs after extraction. The following images correspond to increasing level of BOP: A -156 kPa, B – 162 kPa, C – 180 kPa, and D -182 kPa.

Figure 3

(A) HE staining of median lobe of animals exposed to blast. Images 1 and 3 are taken from an animal in a lower pressure group that remained alive following the blast. Images 2 and 4 are from an animal in a higher pressure group which died within one hour following blast. (B) Graph depicts the Integrated Intensity/Area vs. Peak BOP for animals which survived one hour. Integrated intensity normalized to the area of the image was used to characterize the amount of bleeding within the median lobe.

Figure 4

(A) Probability of Lethality versus Peak BOP for the experimental results obtained in this study. (B) The results from literature are included for comparison of the risk curve [, , –, –, –24].