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
-
Cytokines and eicosanoids are well documented important mediators of endotoxemia. Bicyclic imidazoles are a novel class of nonsteroidal anti-inflammatory compounds that display unique pharmacological profiles by reducing cytokine production and arachidonic acid metabolism. In this study, we evaluated the ability of the bicyclic imidazole, SK&F 86002, to attenuate endotoxin-induced cardiopulmonary dysfunction. ⋯ SK&F 86002 blocked the LPS-induced increase in myeloperoxidase activity, indicating a reduction in pulmonary neutrophil infiltration, but had no effect on systemic leukopenia. Pretreatment with SK&F 86002 significantly attenuated LPS-induced increases in plasma thromboxane B2 and tumor necrosis factor-alpha. We hypothesize that ameliorating effects of SK&F 86002 in this endotoxin model of cardiopulmonary dysfunction are related to inhibition of cytokine and eicosanoid biosynthesis.
-
Comparative Study
Hypertonic saline/dextran treatment for severe pressure-driven hemorrhage in dehydrated conscious swine.
Although dehydration impairs the response to a fixed volume hemorrhage, both 7.5% hypertonic saline/6% dextran 70 (HSD: 4 mL/kg) and standard Ringer's lactate (33 mL/kg) are effective resuscitation fluids. However, the efficacy of resuscitation during continuing hemorrhage remains in question. Using a conscious swine model of continuous pressure-driven hemorrhage, we evaluated the effects of dehydration and HSD resuscitation on survival time, hemorrhage volume, regional blood flows, and central hemodynamics. ⋯ Compared with the EC group, DC had a greater increase in heart rate and arterial base deficit in response to the pressure-driven hemorrhage and a reduced pH and survival time (159 vs. 107 min). In contrast to the DC group, D + HSD had increased mean arterial pressure, cardiac output, oxygen delivery, and regional blood flows to the gut (superior mesenteric artery), kidneys, liver (hepatic artery), and adrenals at 5 min after HSD resuscitation. The HSD did not increase blood loss but tended to prolong survival (+26 min; p = .1079). thus, dehydration compromises survival time (-33%) and the hemodynamic and metabolic responses to pressure-driven hemorrhage, while treatment with HSD improves the hemodynamic responses.
-
Imidazole compounds have been shown to be beneficial in systemic sepsis and inflammation. The purpose of this study was to delineate the effects of fluconazole on systemic hemodynamics and on microanatomy of the heart, lung, liver, and kidney parenchyma of swine during graded bacteremia. Eighteen adult swine were studied in three groups: 1), anesthesia control; 2), septic control (Aeromonas hydrophila, 10(9)/mL, infused i.v. for 4 h); 3) fluconazole (fluconazole, 30 mg/kg i.v., followed by A. hydrophila infusion). ⋯ Tissue oxygen metabolism might be down-regulated by fluconazole. However, preinfusion of fluconazole appears to normalize the sepsis-induced increase in pulmonary alveolar wall thickness. The net significance of these changes on clinical outcome is not clear from these data.
-
Multiple nonpulmonary organ dysfunction is frequently associated with acute lung injury; however, the mechanisms underlying the pathogenesis of this process are not completely understood. Decreased oxygen delivery to distant organs due to maldistribution of blood flow may be a contributing factor. We examined the effects of acute lung injury induced by smoke inhalation on microvascular blood flow to various organs in sheep. ⋯ Blood flow to ileum, colon, spleen, and pancreas was significantly decreased, particularly at 36 and 48 h after injury. These decreases were independent of changes in cardiac output or systemic oxygen delivery. It is likely that alteration in microvascular blood flow may contribute to the development of nonpulmonary organ dysfunction after acute lung injury.
-
To test the hypothesis that brain injury impairs control of vascular tone during compensation from hemorrhagic shock, Sprague-Dawley rats underwent fluid-percussion brain injury (or sham injury control) followed by a stepwise hemorrhage period to 1/2 baseline mean arterial pressure (1/2 MAP), a shock period holding at 1/2 MAP for 30 min, and a resuscitation period. Aortic blood flow (ABF) was measured and vascular conductance (ABF/MAP) was calculated. No differences occurred between groups during the stepwise hemorrhage period. ⋯ In contrast, brain-injured animals increased conductance from .21 +/- .07 to .24 +/- .06 (p < .05) during the shock period and required repeated fluid replacements (3.0 +/- 1.3 cc lactated Ringer's (LR), p < .05) to maintain 1/2 MAP. Following resuscitation, conductance appropriately increased to .31 +/- .05 in controls but did not change (.25 +/- .04, p < .05) in brain-injured animals. We conclude that brain injury adversely affects control of vascular tone during shock and resuscitation in this model.