The Evolution of Isolated Bilateral Lung Contusion From Blunt Chest Trauma in Rats: Cellular and Cytokine Responses

Abstract

Lung contusion is the leading cause of death from blunt thoracic trauma in adults, but its mechanistic pathophysiology remains unclear. This study uses a recently developed rat model to investigate the evolution of inflammation and injury in isolated lung contusion. Bilateral lung contusion with minimal cardiac trauma was induced in 54 anesthetized rats by dropping a 0.3-kg hollow cylindrical weight onto a precordial shield (impact energy, 2.45 Joules). Arterial oxygenation, pressure-volume (P-V) mechanics, histology, and levels of erythrocytes, leukocytes, albumin, and inflammatory mediators in bronchoalveolar lavage (BAL) were assessed at 8 min, at 4, 12, 24, and 48 h, and at 7 days after injury. The role of neutrophils in the evolution of inflammatory injury was also specifically studied by depleting these cells with intravenous vinblastine before lung contusion. Arterial oxygenation was severely reduced at 8 min to 24 h postcontusion, but became almost normal by 48 h. Levels of erythrocytes, leukocytes, and albumin in BAL were increased at <or=24 h, and returned toward normal by 48 h. Deficits in P-V mechanics were most apparent at 24 h postcontusion. Levels of macrophage inflammatory polypeptide-2, cytokine-induced neutrophil chemoattractant-1, and interleukin 6 in BAL peaked at 24 h, whereas monocyte chemoattractant protein-1 and interleukin 1beta peaked at 24 to 48 h postcontusion. Histology showed early hemorrhagic injury (8 min-12 h), with neutrophilic infiltration at 24 h and areas of bronchiolitis obliterans organizing pneumonia-associated fibrosis at 7 days. Vinblastine-treated neutropenic rats had significantly reduced lung injury based on total lung volume at 4 h and on BAL albumin levels at 24 h postcontusion. Inflammatory injury from isolated bilateral lung contusion in rats is most severe in the acute period (8 min-24 h) after initial blunt trauma, and includes a component of neutrophil-dependent pathology.

The role of thoracic trauma in inflammatory responses, apoptosis and bacterial translocation following multipl trauma

“…It has also been reported that anti-IL-10 treatment reduced apoptosis in patients with post-traumatic pulmonary dysfunction. [15] On the contrary, Raghavedran et al [3] showed in their experimental thoracic trauma model that levels of IL-10 in BALF did not significantly increase. Murphy et al [21] on the other hand, reported a significant increase in IL-10 levels in the blood of trauma patients.…”

“…This data suggests that additional processes should be investigated in order to clarify lung injury and causes of morbidity. [3][4][5] These studies also reported that TNF-α and IL-1ß were primary mediators in the activation of other cytokines, and ensured prostaglandin release, synthesis of pro-coagulant factors and activation of leukocyte chemotaxis with adhesion molecules like ICAM and E-selectin. Accumulation of neutrophils increases the production and release of vasoactive substances (leukotrienes, eicosanoids, platelet-activating factor) and proteolytic enzymes (elastase, cathepsin G).…”

“…[1,3,15] Previous studies have reported that the first organ to fail after trauma is the respiratory system, which serves as a pacemaker in the development of MOF. [1] It has been noted in a clinical study that if patients with head trauma also had lung injury, a significant increase was seen in their morbidity, length of hospital stay and mortality.…”

“…Furthermore, it was noted that apoptosis following thoracic traumas may be associated with the inflammatory response. [3][4][5][6] Bacterial translocation refers to the spread of bacteria and their products in the intestinal flora to solid organs, which can be due to intestinal hypoperfusion, burns and stress. Bacterial translocation has been cited as one of the leading factors in the development of acute lung injury, MOF and sepsis.…”

Association of dynamic changes in serum cytokine levels with the severity of injury in patients suffering from closed chest traumas complicated with pulmonary contusions

“…Further clinical analysis confirmed that such a ratio was an important measure for predicting mortality secondary to pulmonary contusion. in a simple pulmonary contusion animal model, the most massive pathological response was found to occur within 8 min to 24 h following trauma, when arterial oxygenation decreased aggressively and the il-6 level in bronchial alveolar lavage fluid increased rapidly to a peak level (8). Kang et al (9) reported that in traumatized rodents, middleaged animals exhibited higher tnF-α, il-6 and il-10 levels than young animals, suggesting the association of cytokine secretion with age.…”