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
-
Comparative Study
Hepatic apoptosis postburn is mediated by c-Jun N-terminal kinase 2.
The trauma of a severe burn injury induces a hypermetabolic response that increases morbidity and mortality. Previously, our group showed that insulin resistance after burn injury is associated with endoplasmic reticulum (ER) stress. Evidence suggests that c-Jun N-terminal kinase (JNK) 2 may be involved in ER stress-induced apoptosis. ⋯ As expected, apoptosis in the liver increased after burn injury in wild-type mice but not in JNK2. Aspartate aminotransferase/alanine aminotransferase activity revealed that liver function recovered more quickly in JNK2. This study indicates that JNK2 is a central mediator of hepatic apoptosis after a severe burn.
-
Hemorrhagic shock (HS)-induced microvascular hyperpermeability poses a serious challenge in the management of trauma patients. Microvascular hyperpermeability occurs mainly because of the disruption of endothelial cell adherens junctions, where the "intrinsic" apoptotic signaling plays a regulatory role. The purpose of this study was to understand the role of the "extrinsic" apoptotic signaling molecules, particularly Fas-Fas ligand interaction in microvascular endothelial barrier integrity. ⋯ FasFc treatment showed protection against HS serum-induced disruption of the adherens junctions and monolayer hyperpermeability (P < 0.05) in the endothelial cells. Pretreatment with FasFc also decreased HS serum-induced increase in mitochondrial reactive oxygen species formation, restored HS serum-induced drop in mitochondrial transmembrane potential, and reduced HS serum-induced caspase 3 activity in RLMECs. These findings open new avenues for drug development to manage HS-induced microvascular hyperpermeability by targeting the Fas-Fas ligand-mediated pathway.
-
Animal models of combined traumatic brain injury (TBI) and hemorrhagic shock (HS) suggest a benefit of hemoglobin-based oxygen carrier (HBOC)-based resuscitation, but their use remains controversial, and little is known of the specific effects of TBI and high-pressure (large arterial injury) bleeding on resuscitation. We examine the effect of TBI and aortic tear injury on low-volume HBOC resuscitation in a swine polytrauma model and hypothesize that HBOC-based resuscitation will improve survival in the setting of aortic tear regardless of the presence of TBI. Anesthetized swine subjected to HS with aortic tear with or without fluid percussion TBI underwent equivalent limited resuscitation with HBOC, lactated Ringer's solution, or HBOC + nitroglycerine (vasoattenuated HBOC) and were observed for 6 h. ⋯ However, total catheter hemorrhage volume required to reach target shock blood pressure was less with TBI (14.0 mL · kg(-1) [confidence interval, 12.4-15.6 mL · kg(-1)]) versus HS only (21.0 mL · kg(-1) [confidence interval, 19.5-22.5 mL · kg(-1)]), with equivalent lactate accumulation. Traumatic brain injury did not affect survival in this polytrauma model, but less hemorrhage was required in the presence of TBI to achieve an equivalent degree of shock suggesting globally impaired cardiovascular response to hemorrhage in the presence of TBI. There was also no benefit of HBOC-based fluid resuscitation over lactated Ringer's solution, contrary to models using liver injury as the source of hemorrhage, considering wound location is of paramount importance when choosing resuscitation strategy.
-
Off-pump coronary artery bypass surgery induces prolonged alterations to host neutrophil physiology.
Persistent alteration to host polymorphonuclear cell (PMN) physiology has been demonstrated after cardiac surgery performed with cardiopulmonary bypass (CPB). However, to date, PMN physiology and function beyond the first 24 h have not been investigated after cardiac surgery performed without CPB (off-pump coronary artery bypass grafting [OPCAB]). Blood samples of 15 patients were collected preoperatively and on days 1, 3, and 5 after OPCAB. ⋯ Under resting conditions, PMN CD11b, CBRM1/5, and CD62L expressions were minimally altered by surgery. Compared with the response of preoperative PMNs, PMNs assayed on days 3 and 5 after OPCAB demonstrated a significantly blunted increase in the expression of CD11b and CBRM1/5 after fMLF, significantly diminished shedding of CD62L in response to platelet-activating factor and fMLF, and diminished superoxide production after stimulation on day 3. The alteration of PMN function after OPCAB implies that cardiac surgical trauma without CPB directly modulates host PMN physiology.
-
Review
Tranexamic acid and trauma: current status and knowledge gaps with recommended research priorities.
A recent large civilian randomized controlled trial on the use of tranexamic acid (TXA) for trauma reported important survival benefits. Subsequently, successful use of TXA for combat casualties in Afghanistan was also reported. As a result of these promising studies, there has been growing interest in the use of TXA for trauma. ⋯ A US Department of Defense committee conducted a review and assessment of knowledge gaps and research requirements regarding the use of TXA for the treatment of casualties that have experienced traumatic hemorrhage. We present identified knowledge gaps and associated research priorities. We believe that important knowledge gaps exist and that a targeted, prioritized research effort will contribute to the refinement of practice guidelines over time.