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
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This study was performed to determine whether endotoxemia causes diastolic cardiac dysfunction. Eleven healthy volunteers, 30 +/- 6 years of age, underwent comprehensive transthoracic echocardiographic assessment including two-dimensional, M-mode transmitral and tissue Doppler of systolic and diastolic function at baseline and at 3 and 5 h after intravenous administration of purified Escherichia coli endotoxin (4 ng/kg). Data were analyzed by analysis of variance; P values of less than 0.05 were considered significant. ⋯ The observed decreases in E/A (transmitral) and E/A (tissue Doppler) ratio were primarily due to increases in A and A. Moreover, isovolumic relaxation time and time constant for left ventricular relaxation, a load-independent parameter for ventricular relaxation, remained unchanged at 3 and 5 h after endotoxin infusion. Therefore, our findings are more likely due to enhanced atrial contractility resulting from increased sympathetic activity in response to reduction in left ventricular afterload and not due to altered diastolic filling characteristics.
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Administration of a single bolus of endotoxin is a model of sepsis response in experimental animal studies. Large animal species, such as pigs and sheep, are more sensitive to endotoxin administration due to an initial excessive pulmonary hypertensive response frequently resulting in acute right heart dysfunction. We investigated whether infusion of high-dose endotoxin in pigs but administered in an increasing dose results in inflammatory response without excessive pulmonary hypertension and right heart dysfunction. ⋯ In contrast, plasma levels of nitrite/nitrate, IL-1ra (as marker of cytokine response), remained markedly increased at 5 h after endotoxin infusion as compared with baseline values. Plasma markers of organ damage were significantly increased. Our data show that the dosing of endotoxin in an increasing manner in pigs produces a reliable model of an experimental sepsis response and organ dysfunction without immediate overwhelming pulmonary hypertension resulting in cardiovascular failure.
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Leptin is a pleiotrophic protein mainly produced by adipocytes that has been implicated as a link between nutritional status and immune function. Severe bacterial infection is associated with elevated plasma levels of leptin. To determine the role of leptin in the host response to bacterial pneumonia leptin deficient ob/ob mice and normal wild-type (WT) mice were intranasally infected with different doses of the Gram-positive pathogen Streptococcus (S.) pneumoniae or the Gram-negative bacterium Klebsiella (K.) pneumoniae. ⋯ In addition, the extent and severity of lung inflammation, as assessed by semi-quantitative histopathology scores, were similar in both mouse strains. Finally, leptin deficiency did not impact on the bacterial outgrowth in the lungs during either Gram-positive or Gram-negative pneumonia irrespective of the infective dose. These data suggest that although leptin may play a modest role in the regulation of inflammation during bacterial pneumonia, it does not contribute to host defense mechanisms that act to limit the outgrowth of S. pneumoniae or K. pneumoniae in the lower airways.
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Intercellular adhesion molecule 1 (ICAM-1) plays an important role in the transmigration of polymorphonuclear neutrophils (PMN) in sepsis. Moreover, the transmigration rate of leukocytes from the blood via endothelial adhesion molecules into tissues correlates with the severity of multi organ failure. We examined the effect of the deletion of the ICAM-1 gene in polymicrobial sepsis using a cecal ligation and puncture (CLP) sepsis model in mice. ⋯ The DTH reaction was significantly decreased in ICAM-1-/- mice versus WT mice (0.34 vs 0.41 mm; P < 0.05). Our results demonstrate a significant reduction of mortality after septic challenge in ICAM-1-/- mice compared to normal mice. This is associated with a decrease in lymphocyte subpopulations, cytokine levels, and DTH type 4 reaction, possibly reflecting an overall attenuation of the immune system.
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Hemorrhage remains a primary cause of death in civilian and military trauma. Permissive hypotensive resuscitation is a possible approach to reduce bleeding in patients until they can be stabilized in an appropriate hospital setting. Small-volume resuscitation with hypertonic saline (HS) is of particular interest because it allows one to modulate the inflammatory response to hemorrhage and trauma. ⋯ Despite the strong effects of HS and HHES on cytokine production, both treatments had little effect on plasma lactate, base excess (BE), white blood cell (WBC) count, myeloperoxidase (MPO) content, and the wet/dry weight ratio of the lungs. Moreover, on day 7 after shock, the survival rate in rats treated with HS was markedly, but not significantly, lower than that of NS-treated animals (47% vs. 63%, respectively). In summary, hypotensive resuscitation with hypertonic fluids reduces the inflammatory response but not lung tissue damage or mortality after severe hemorrhagic shock.