The Endothelin Axis and Gelatinase Activity in Alveolar Macrophages After Brain-stem Death Injury: A Pilot Study

A Sphingosine 1–Phosphate 1 Receptor Agonist Modulates Brain Death–Induced Neurogenic Pulmonary Injury

“…However, the early autonomic storm accompanying brain BD triggers the development of systemic and pulmonary inflammatory responses, which lead to increased pulmonary endothelial permeability (1,2) and to the sympathetic vasoconstriction of the systemic and pulmonary vasculature. These changes, in addition to possible ischemiareperfusion injury, disrupt the integrity of the alveolar capillary membrane, resulting in neurogenic pulmonary edema (NPE) (1)(2)(3)(4). Increased pulmonary interstitial and alveolar fluid accumulation usually develops rapidly after acute injury to the central nervous system (1), and any preventive treatment should be given early after BD (3).…”

The implications of brain death in donor lung injury: investigation and blockade of the endothelin axis

“…[210] Animal experiments have shown that ET-1 is upregulated in serum and in donor lung after BD and that this is related to MMP activation. [88,211] Salama et al demonstrated a correlation between donor ET-1 and primary graft dysfunction (PGD). [212] In this study,…”

“…[88] These cells play an integral role in inflammatory responses to various stimuli; through multiple cell surface receptors and a significant armamentarium of inflammatory mediators, macrophages can contribute directly to pulmonary inflammation, or act to recruit neutrophils and further drive the inflammatory process. [316,317] Gibbs et al identified a link between alveolar macrophages and gelatinase expression in lung injury in rats, which was similar to that seen in the human lung.…”

“…[317] This observation was extended to the brain death model by the Sutherland study. [88] Other authors have identified the relationship between alveolar macrophages, pulmonary IRI and free oxygen radical generation. [318,319] These findings have lead to the conclusion that resident tissue inflammatory cells, including pulmonary macrophages, may be primed prior to transplantation, and that these cell populations may be the initiators of early lung injury after transplant.…”

“…[318,319] These findings have lead to the conclusion that resident tissue inflammatory cells, including pulmonary macrophages, may be primed prior to transplantation, and that these cell populations may be the initiators of early lung injury after transplant. [24,318] The selection of a dual endothelin receptor antagonist was therefore based on the observations that alveolar macrophages express both endothelin receptors after brain death [88] and that they contribute significantly to post-transplant pulmonary injury. [318] Endothelin antagonists have been investigated in a wide variety of conditions, including pulmonary hypertension, [108] sepsis, [74] pain, [80] cancer, [84,111] meconium aspiration, [320] heart failure, [321,322] and cerebral vasospasm amongst others.…”