Approximately 25–50% of all injuries involve thoracic trauma [
72]. The most frequently used small animal models for blunt chest trauma are captive bolt handgun [
14], weight drop (maximum energy equivalent 2.45 J, mortality 33%) [
73] and blast wave [
74‐
76], resulting in pulmonary contusion and in systemic and local inflammation. To prevent an associated cardiac injury, in weight-drop models an additional protective shield is utilized [
73,
77], whereas cardiac injuries can be detected in models induced by blast wave [
78]. Functionally, correlation between the volume of the lung contusion and dysfunction are similarly limited in rats and humans [
79,
80]. Clemedson and Pettersson already described in 1953 the mechanical forces that are relevant for lung contusion, with subsequently disrupted alveoli and small airways by shearing forces as well as for stripping of alveolar tissue from heavier hilar structures, caused by acceleration at different rates [
81]. Increased cytokine and chemokine concentrations in bronchoalveolar lavage fluid (BAL) have been found after trauma in rats as well as in the human situation [
73,
82,
83]. Neutrophil infiltration was detected in lung tissue in rats after blast injury [
74], whereas neutrophil depletion significantly reduced lung injury based on BAL albumin concentrations post contusion [
73]. Furthermore, chemotactic and phagocytic activity of alveolar macrophages was increased after blunt chest trauma, which is again similar to humans [
82,
84]. Modeling blunt chest trauma in rats is well defined and standardized, however, there are some differences between rats and humans to be considered when interpreting data. One divergence is based on differences in toll-like receptors (TLRs) and thus in the recognition of endotoxins and damage-associated molecular patterns (DAMPs) [
85]. In the extracellular domain of TLR4, humans and rats share only 61% total amino acid similarity [
86]. Moderate levels of TLR4 expression were detected in human lungs, whereas human alveolar epithelial type II cells and alveolar macrophages have been shown to mainly express TLR2 [
87]. In contrast to human dendritic cells (DC), all rat DC subsets and monocytes from Sprague–Dawley, Lewis and Brown Norway rats express TLR4 [
85]. Therefore, when using trauma rat models for the prediction of human responses to TLRs agonists, scientists should be aware of the inherent limitations of rat studies. Even the discussed presence of pulmonary intravascular macrophages (PIM) [
88], constitutive or inducible in humans and in rats respectively, may contribute to species-dependent differences in the sensitivity to endotoxin-induced lung injury [
89]. Additionally, previous data have shown similarities in the histological appearance of CD68-positive intravascular cells in human and rat lungs of hepatopulmonary syndrome [
90]. Lipofibroblasts are another cell population known in the lungs of rats (and mice), but is still under debate for human lungs [
91]. Furthermore, nitric oxide (NO) is an important mediator of numerous physiologic and inflammatory processes in the lung. Constitutive NOS (cNOS) has been found in human lung nerves and large-vessel endothelium, but was lacking in the airway and alveolar epithelia. In rats, cNOS was found in lung nerves, endothelium and alveolar epithelium [
92]. Inducible NOS (iNOS) was expressed in human alveolar macrophages during chronic inflammation and, quite similarly, in rat macrophages after lipopolysaccharide (LPS) treatment [
92]. Rat and human neutrophils have been shown to produce comparable amounts of NO, but much less than rodent macrophages [
93]. With regard to anatomical differences between rat and human lungs, airway branching in humans is more dichotomous and symmetric, whereas rat lungs are more monopodial [
94]. The latter might need to be considered when studying air flow distribution, gas uptake and aspiration. Furthermore, severe blunt chest trauma is also associated with cardiac inflammation and structural alteration of cardiac tissue in rats [
78]. Rats with blast wave-induced blunt chest trauma displayed acute cardiac tissue damage as well as increased concentrations of circulating heart fatty acid binding protein (H-FABP). Furthermore, rats exhibited increased local cardiac inflammation by increased interleukin (IL)-1β levels as well as disturbed cardiac gap-junction architecture [
78]. Moreover, increased blood levels of the N-terminal pro-B-type natriuretic peptide after blunt chest trauma in rats was correlated with a blunt-induced cardiac trauma [
95]. However, when modeling cardiac damage after blunt chest trauma, differences between the respective rat strains as well as gender differences within the same rat strain should be carefully considered. Male Sprague–Dawley, Wistar and Wistar-Kyoto rats have low initial serum cardiac troponin I levels, whereas Spontaneous Hypertensive and Fisher rats have high baseline troponin I levels. Furthermore, the baseline troponin I levels differ within the same rat strain between the male and female. Thereby, female rats of the Spontaneous Hypertensive, Sprague–Dawley and Wistar displayed significantly lower troponin I baseline levels compared to the respective male rats. Moreover, testosterone and estrogen levels might also influence the presence of systemic cardiac troponin I. In male Spontaneous Hypertensive rats, the serum troponin I levels significantly increased after castration, whereas in ovariectomized female Spontaneous Hypertensive rats, the systemic troponin I concentrations were significantly reduced [
96].