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
-
Hemorrhagic shock (HS) is associated with the disruption of endothelial cell barrier leading to vascular hyperpermeability. Previous studies from our laboratory implicate reactive oxygen species (ROS) and the intrinsic apoptotic signaling cascades as mediators of vascular hyperpermeability after HS. Here we report the protective effects of alpha-lipoic acid, a natural antioxidant with antiapoptotic properties, against vascular hyperpermeability after HS. ⋯ Hemorrhagic shock resulted in vascular hyperpermeability and mitochondrial ROS formation. The activation of mitochondrial intrinsic apoptotic signaling pathway was evidenced from mitochondrial depolarization, an increase in cytochrome c release, and activation of caspase 3. alpha-Lipoic acid (100 mg/kg) given before the shock period attenuated vascular hyperpermeability, mitochondrial ROS formation, mitochondrial depolarization, cytochrome c release, and activation of caspase 3 (P < 0.05). Together, these results demonstrate that alpha-lipoic acid provides protection against vascular hyperpermeability by modulating the mitochondrial "intrinsic" apoptotic signaling.
-
Alveolar type 2 (AT-2) cell apoptosis is an important mechanism during lung inflammation, lung injury, and regeneration. Blunt chest trauma has been shown to activate inflammatory cells such as alveolar macrophages (AMs) or neutrophils (polymorphonuclear granulocytes [PMNs]), resulting in an inflammatory response. The present study was performed to determine the capacity of different components/cells of the alveolar compartment (AMs, PMNs, or bronchoalveolar lavage [BAL] fluids) to induce apoptosis in AT-2 cells following blunt chest trauma. ⋯ In contrast, no apoptosis was induced in AT-2 cells incubated with supernatants of activated PMNs or BAL fluids of traumatized animals. In summary, blunt chest trauma induced apoptosis in AT-2 cells, possibly involving the extrinsic death receptor pathway. Furthermore, mediators released by AMs appeared to be involved in the induction of AT-2 cell apoptosis.
-
Hemodynamic support of patients with septic shock is often complicated by a tachyphylaxis against exogenous catecholamines. Because an increase in somatotropic hormones may play a pivotal role in the regulation of the inflammatory response to endotoxin, intravenous supplementation of the neuroendocrine hormone somatostatin (SOMA) may attenuate hemodynamic dysfunction resulting from endotoxemia. The objective of the present study was to assess the short-term effects of SOMA alone and in combination with norepinephrine (NE) on cardiopulmonary hemodynamics, global oxygen transport, plasma nitrate/nitrite levels, and intestinal integrity compared with single NE therapy in ovine endotoxemia. ⋯ In conclusion, short-term treatment with SOMA failed to attenuate cardiocirculatory shock resulting from endotoxemia and did not improve vasopressor response to NE. In addition, combined SOMA and NE therapy resulted in intestinal injury. Therefore, SOMA does not seem to represent a therapeutic option to treat arterial hypotension resulting from sepsis and systemic inflammatory response syndrome.
-
Thermal injuries greater than 20% body surface area (BSA) result in systemic shock with generalized edema in addition to local tissue destruction. Burn shock is induced by a variety of mediators, mainly immunomodulative cytokines. This experimental study evaluates if burn shock can be induced in healthy rats by transfer of burn plasma (BP) with mediators. ⋯ The burned tissue is no longer required for burn shock induction, and the pathophysiologic process seems to be self-perpetuating as early as 4 h posttrauma. Leukocytes are activated by thermal injury and BP infusion. The role of leukocyte-endothelium interactions for edema formation remains uncertain and requires further investigation.