Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
-
Programmed death 1 (PD-1) is an inhibitor protein receptor for the immune system and has been shown to be upregulated in animal models of critical illness as well as after trauma and in burn victims in humans. It is believed that PD-1 may play a role in the immune dysfunction seen in surgical critical illness. However, although prior studies have associated changes in PD-1 expression with altered immune cell function, it is not known if a correlation with clinical status exists. ⋯ In addition, among patients with an APACHE II score of greater than 20, there was a larger percentage of CD3 cells (44% vs. 29%; P = 0.015) expressing PD-1. When only patients with an APACHE II score greater than 20 were assessed, PD-1 expression on monocytes correlated positively with interleukin levels in the serum (r = 0.525, P = 0.05). Variability in the expression of PD-1 on leukocytes in critical surgical illness correlates with physiological dysfunction and suggests that PD-1 may be a valuable tool in the assessment of immune dysfunction following trauma or severe surgical insult.
-
Vascular hyporeactivity is an important factor in irreversible shock, whereas calcium desensitization is one of the mechanisms of vascular hyporeactivity, and the intestinal lymphatic pathway plays an important role in multiple organ injury after severe hemorrhagic shock (HS). In this study, our aims were to determine the effects of mesenteric lymph on vascular reactivity during HS and the mechanisms involved. First, the in vivo pressor response was observed by intravenous injection of norepinephrine (3 μg/kg) at different time points after HS. ⋯ These results indicate that mesenteric lymph return plays an important role in biphasic changes in vascular reactivity during HS. Even more importantly, mesenteric lymph 1 h after shock was an important contributor to vascular hyporeactivity, and its mechanism of action was related to calcium desensitization. Targeting lymph may therefore have therapeutic potential in the treatment of severe shock-induced hypotension.
-
In bowel ischemia, impaired mucosal integrity may allow intestinal pancreatic enzyme products to become systemic and precipitate irreversible shock and death. This can be attenuated by pancreatic enzyme inhibition in the small-bowel lumen. It is unresolved, however, whether ischemically mediated mucosal disruption is the key event allowing pancreatic enzyme products systemic access and whether intestinal digestive enzyme activity in concert with increased mucosal permeability leads to shock in the absence of ischemia. ⋯ Depletion of plasma protease inhibitors was found only in animals perfused with pancreatic enzymes plus mucin disruption, implicating increased permeability and intralumenal pancreatic enzyme egress in this group. These experiments demonstrate that increased bowel permeability via mucin disruption in the presence of pancreatic enzymes can induce shock and increase systemic protease activation in the absence of ischemia, implicating bowel mucin disruption as a key event in early ischemia. Digestive enzymes and their products, if allowed to penetrate the gut wall, may trigger multiorgan failure and death.
-
17β-Estradiol (E2) treatment activates a set of protective response that has been found to protect cells from injury and more importantly to significantly abate the injuries associated with trauma-hemorrhage in vivo. Rapid NF-κB activation has been found to be an important signaling step in E2-mediated protection in cell culture, in vivo ischemia, and trauma-hemorrhage. In the current study, we investigated the signaling cascades linking E2 signaling with NF-κB activation and the protective response and compared them with the effects of two selective estrogen receptor modulators (SERMs), raloxifene and tamoxifen. ⋯ However, E2, unlike either SERM, led to modest increases in apoptosis through the JNK pathway. Selective estrogen receptor modulator treatment led to increased expression of the protective proteins, Mn superoxide dismutase, and endothelial nitric oxide synthase, which was not seen with E2. These results provide new insight into the pathways activating NF-κB by E2 and SERMs and demonstrate that SERMs may have greater protective benefits than E2 in adult endothelial cells and potentially in vivo, as well.
-
Sepsis is the leading cause of mortality in intensive care units. Early detection and intervention are critical to prevent death. The acute radiation syndrome is characterized by damage of the gastrointestinal and hematopoietic systems. ⋯ Moreover, plasma PCT levels were elevated already from day 3.5 onward, whereas LPS was elevated from day 7 and LPS-binding protein only 10 days after TBI. Receiver operating characteristic analysis revealed that PCT levels measured 3.5 days after TBI predicted lethality at 10 days. These data demonstrate the value of PCT as an early biomarker in radiation-induced bacteremia for mouse studies and suggest that clinical results from other septic conditions may apply to postradiation septicemia in humans.