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- Author or Editor: Yoko Sakaue x
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Objective—To determine the effects of continuous low-dose infusion of lipopolysaccharide (LPS) on the expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1) mRNA and neutrophil accumulation in the lungs, liver, spleen, small intestine, and pancreas in dogs.
Animals—11 healthy adult Beagles.
Procedure—Dogs received a continuous infusion of a low dose (10 µg/kg/h, IV) of LPS ( Escherichia coli055:B5) or saline (0.9% NaCl) solution (20 mL/kg/h, IV) for 8 hours. Activity levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) and the number of WBCs in circulation were examined before and 1, 2, 4, and 8 hours after the onset of LPS infusion. Expression of E-selectin and ICAM-1 mRNA and the number of neutrophils in each tissue were examined.
Results—After the onset of LPS infusion, serum TNF-α and IL-1β activities transiently increased. Thereafter, IL-6 activity increased, and high IL-6 activity was maintained throughout the experiment. In dogs in the LPS group, expression of E-selectin mRNA increased only in the lungs, and expression of ICAM-1 mRNA increased in the lungs and liver; the number of neutrophils in the tissue increased in the lungs and liver.
Conclusions and Clinical Relevance—Results suggested that expression of E-selectin and ICAM-1 mRNA increased during sepsis, particularly in the lungs and liver, and that this increase was associated with neutrophil accumulation. Hence, inhibiting the activation of endothelial cells in the lung and liver may decrease organ damage caused by accumulated neutrophils and help regulate multiple-organ dysfunction. (Am J Vet Res 2005;66:1259–1266)
Objective—To determine whether continuous infusion of a low dose of lipopolysaccharide (LPS) to induce a condition mimicking septic shock in dogs would affect systemic and hepatosplanchnic circulation and oxygenation.
Animals—12 healthy adult Beagles.
Procedure—Dogs received a low dose of LPS (Escherichia coli O55:B5) by continuous IV infusion at a rate of 1 µg/kg/h for 8 hours. Systemic hemodynamics; systemic oxygenation; blood flow in the cranial mesenteric artery, common hepatic artery, and portal vein; intestinal and hepatic tissue blood flow; mesenteric oxygenation; and intramucosal PCO2 were examined before and at selected time points after onset of the LPS infusion.
Results—After onset of the LPS infusion, cardiac index increased and mean arterial pressure (MAP) and systemic vascular resistance decreased, which is characteristic of the hyperdynamic state in septic patients. Hepatosplanchnic blood flow increased during the hyperdynamic state. Intestinal PCO2 was increased even when blood flows increased. During the latter half of the experimental period, MAP was maintained but hepatosplanchnic blood flows decreased and intestinal PCO2 increased further.
Conclusions and Clinical Relevance—Analysis of the results suggested that hepatosplanchnic blood flow enters the hyperdynamic state during the early stages of sepsis and that intestinal tissue oxygenation is threatened even when hepatosplanchnic blood flow is increased or maintained. Hence, improvement of hepatosplanchnic circulation and intestinal tissue oxygenation is important in dogs with clinical evidence of a septic condition. (Am J Vet Res 2004;65:1347–1354)
Objective—To determine whether small intestinal ischemia and reperfusion affects intestinal intramucosal pH (pHi), arterial and portal venous blood gas values, and intestinal blood flow (IBF) and to investigate relationships between regional intestinal tissue oxygenation and systemic variables in dogs.
Animals—15 healthy adult Beagles.
Procedure—Occlusion of superior mesenteric artery (SMA) for 0, 30, or 60 minutes, followed by reperfusion for 180 minutes, was performed; IBF, pHi, arterial and portal venous blood gas values, arterial pressure, and heart rate were measured at various time points; and intestinal mucosal injury was histologically graded.
Results—Occlusion of the SMA induced significant decreases in pHi and IBF. After the release of the occlusion, IBF returned rapidly to baseline values, but improvement in pHi was slow. Arterial and portal venous blood gas analyses were less sensitive than tonometric measurements of pHi, and there was no correlation between results of blood gas analyses and tonometric measurements. Histologic score for intestinal mucosal injury increased significantly, depending on duration of ischemia, and there was a correlation between tonometric results and the histologic score.
Conclusion and Clinical Relevance—Results suggest that it is difficult to accurately evaluate local oxygenation disorders by monitoring at the systemic level, whereas clinically pHi is the only reliable indicator of inadequate regional intestinal tissue oxygenation in dogs. (Am J Vet Res 2002;63:804–810)
Objective—To determine whether small intestinal ischemia and reperfusion induces bacterial translocation and proinflammatory cytokine response in either the systemic or portal circulation in dogs.
Animals—17 healthy adult Beagles.
Procedure—The superior mesenteric artery (SMA) was occluded for 0 (group-3 dogs), 30 (group-1 dogs), or 60 (group-2 dogs) minutes, followed by reperfusion for 180 minutes; serum lactate and endotoxin concentrations and tumor necrosis factor-α (TNF-α), interleukin- 1β (IL-1β), and IL-6 activities in the systemic and portal circulation and intramucosal pH were measured at various time points.
Results—In group-2 dogs, TNF-α activity was found to be significantly increased in the portal circulation, peaking at 60 minutes of reperfusion; TNF-α activity, in the systemic circulation, gradually increased from 60 minutes of reperfusion to the end of the experiment; however, the increase was not significant. In group-1 and -2 dogs, IL-6 activities significantly and gradually increased in the systemic and portal circulation during the reperfusion phase, and the magnitude of these increases was dependent on the duration of the ischemic phase. There were no significant changes in IL-1β activity or endotoxin concentration in any dog group.
Conclusions and Clinical Relevance—Results of the our study indicate that intestinal ischemia and reperfusion leads to significant increases of the circulating TNF-α and IL-6 activities, depending on the duration of the ischemia phase, in the absence of detectable endotoxin in the circulation. This finding suggests that intestinal ischemia and reperfusion induces a systemic proinflammatory cytokine response in dogs. (Am J Vet Res 2002;63:1680–1686)