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
-
Mesenteric hypoperfusion due to circulatory shock is a key event in the pathogenesis of subsequent distant organ injury. Postshock mesenteric lymph (PSML) has been shown to contain proinflammatory mediators elaborated from the ischemic gut. We hypothesize that the relative bioactivity of PSML depends on the depth and duration of circulatory shock. ⋯ Maximal PSML bioactivity, as measured by PMN priming for the respiratory burst, occurred during the third postshock hour, which correlated with peak lymph flow rate. PSML bioactivity was greatest with 30 mm Hg x 45 min, followed by 30 mm Hg x 15 min, 45 mm Hg x 45 min, and 45 mm Hg x 15 min. Hemorrhagic shock provokes the release of bioactive agents in PSML that is dependent on both depth and duration of shock.
-
The objective of this study was to evaluate the negative regulatory role of heat shock protein 70 (HSP70) on endotoxin-induced activation of inflammatory cytokine signaling pathways in a macrophage cell line. Our studies show that elevation of HSP70 either by activation of the heat shock response (HSR) or through forced expression of the hsp70.1 gene downregulates cytokine expression. Our experiments showed that activation of the HSR and HSP70 overexpression could inhibit LPS-mediated expression of the proinflammatory cytokines TNF-alpha and IL-1 at the mRNA and protein levels. ⋯ Overexpression of HSP70 inhibited the nuclear translocation of p65, the transcriptionally active component of the NF-kappaB complex, and prevented the degradation of IkappaBalpha, the regulator of NF-kappaB activity. However, HSP70 elevation did not markedly inhibit signaling through the MAPK arm of the LPS-induced pathway, suggesting that the effects of HSP70 are mediated primarily through the NF-kappaB cascade. Our experiments therefore suggested that elevated levels of HSP70 inhibit LPS-induced production of inflammatory cytokines by a mechanisms involving inactivation of NF-kappaB but cast doubt on significant role for the MAPK pathway in these effects.
-
Comparative Study
Bovine polymerized hemoglobin versus Hextend resuscitation in a swine model of severe controlled hemorrhagic shock with delay to definitive care.
To compare the efficacy of low-volume resuscitation with bovine polymerized hemoglobin (HBOC-201) versus hetastarch (HEX) in an intermediate severity combat-relevant hemorrhagic shock swine model with a simulated delay to hospital care. Twenty-four anesthetized pigs were hemorrhaged 55% estimated blood volume in conjunction with a 5-min rectus abdominus crush. At 20 min, pigs were resuscitated with 10 mL/kg of HBOC-201 or HEX or nothing (NON); resuscitated pigs received additional infusions (5 mL/kg) at 30, 60, 120, or 180 min if hypotension or tachycardia persisted. ⋯ At simulated hospital arrival, no HBOC-201 pigs required additional fluids or blood transfusion. In contrast, 100% of HEX pigs required blood transfusions (P < 0.01). In this swine model of controlled hemorrhage with low-volume resuscitation and delayed definitive care, HBOC-201 pigs had improved hemodynamics, transcutaneous tissue oxygen tension, and transfusion avoidance compared with HEX.
-
In this study, experiments were designed to determine if peroxisome proliferator-activated receptor (PPAR) alpha agonists could decrease myocardial ischemia/reperfusion injury after cardioplegia-induced cardiac arrest under cardiopulmonary bypass, attenuate the appearance of cardiomyocytic apoptosis, and decrease the damage of reactive oxygen species. Cardiomyocytic apoptosis occurs after cardiopulmonary bypass surgery. Reactive oxygen species and peroxynitrite generated during ischemia/reperfusion initiate the formation of single-strand DNA breaks. ⋯ The occurrence of cardiomyocytic apoptosis and elevation of plasma cytokines were significantly lower in the group receiving PPAR-alpha agonists than in the other groups. Western blot analysis of apoptosis-inducing factor and cytochrome c revealed similar patterns. PPAR-alpha activation could diminish postischemic cardiomyocytic apoptosis and reactive oxygen species injuries after global cardiac arrest under cardiopulmonary bypass, possibly via prevention of both caspase-dependent and caspase-independent apoptotic pathways.
-
Hypertonic saline solutions improve cerebral blood flow (CBF) when used for acute resuscitation from hemorrhagic hypotension accompanying some models of traumatic brain injury (TBI); however, the duration of increased CBF is brief. Because the nitric oxide synthase substrate l-arginine provides prolonged improvement in CBF after TBI, we investigated whether a hypertonic resuscitation fluid containing l-arginine would improve CBF in comparison to hypertonic saline without l-arginine in a model of moderate, paramedian, fluid-percussion TBI followed immediately by hemorrhagic hypotension (mean arterial pressure [MAP] = 60 mm Hg for 45 min). Sprague-Dawley rats were anesthetized with 4.0% isoflurane, intubated and ventilated with 1.5%-2.0% isoflurane in oxygen/air (50:50). ⋯ CBF increased similarly in all groups during infusion and then decreased similarly in all groups. At 120 min after infusion, CBF was highest in the group infused with hypertonic saline, but the difference was not significant. We conclude that the improvement of MAP, ICP, and CBF produced by hypertonic saline alone after TBI and hemorrhagic hypotension is not significantly enhanced by the addition of L-arginine at these doses.