The Journal of surgical research
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Sepsis impairs anastomotic collagen gene expression and synthesis: a possible role for nitric oxide.
Although intra-abdominal sepsis is known to impair colon healing by inhibiting anastomotic collagen synthesis, the effect of systemic sepsis on this process is unknown. Endotoxins and cytokines associated with sepsis induce nitric oxide synthesis both systemically and locally within colonic tissue. We hypothesized that systemic sepsis impairs colonic healing and examined a possible correlation with nitric oxide expression. ⋯ Sepsis elevated nitric oxide synthase activity in anastomotic tissue 24 hr postanastomosis, when compared to sham tissue (P < 0.0001). These data suggest that systemic endotoxin induces nitric oxide synthesis at the anastomotic site. The simultaneous dysregulation of collagen gene expression and synthesis with decreased anastomotic strength suggests a possible regulatory role for nitric oxide in gastrointestinal healing.
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Retroperitoneal and intraperitoneal CO2 insufflation have markedly different cardiovascular effects.
Both retroperitoneoscopic and laparoscopic surgical approaches to kidney and adrenal gland have been reported but their cardiopulmonary pathophysiology has been incompletely characterized. To test the hypothesis that these approaches have markedly different impact on the circulatory and respiratory systems, we assessed at similar insufflation pressures alterations in cardiovascular and respiratory variables during retroperitoneal and intraperitoneal CO2 insufflation. Eighteen healthy, anesthetized (propofol, alfentanil, vecuronium), mechanically ventilated pigs were randomly instrumented for either retroperitoneoscopic (n = 9) or laparoscopic (n = 9) surgery. ⋯ While both retroperitoneal and intraperitoneal CO2 insufflation required increased tidal volumes to adjust endtidal CO2 tension to baseline, intraperitoneal CO2 insufflation resulted in a significantly greater increase of mixed venous and arterial carbon dioxide tensions (P < 0.007) even at similar insufflation pressures. Furthermore, significantly greater peak airway pressures (P = 0.018) were required with intraperitoneal than with retroperitoneal insufflation to administer the same tidal volume, indicating a greater decrease in quasi-static compliance with intraperitoneal insufflation (P = 0.0436). Thus, (i) cardiovascular and respiratory changes are much less during retroperitoneal than intraperitoneal CO2 insufflation, even at the same insufflation pressures, and (ii) retroperitoneal CO2 insufflation unlike intraabdominal CO2 insufflation does not induce an inferior vena caval pressure gradient and hence does not appear to impair systemic lower body venous return up to insufflation pressures of 20 mmHg.
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To determine the contribution of xanthine oxidase-mediated endothelial dysfunction to the blood flow deficits seen in the mesenteric circulation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/hr infusion of the xanthine oxidase inhibitor allopurinol (allo) after shock but before resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group (Std Res) and a nonhemorrhage group served as controls. ⋯ Endothelial-dependent vasodilation and blood flow were preserved in the group receiving Std Res plus allo. The preservation of endothelial function correlated with the restoration of microvascular blood flow postresuscitation. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to endothelial dysfunction and blood flow deficits in the mesenteric microcirculation after resuscitated hemorrhagic shock, the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation.
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Cytokine aberrations may contribute to sepsis-associated mortality after trauma. We have previously documented that IL-10 (a Th-2 cytokine) is downregulated after tissue trauma, and the administration of exogenous IL-10 improved survival and anti-IL-10 antibody increased lethality in a murine injury-lethal endotox-emia model. IL-4 activates the Th-2 subset of T cells, and functions in a paracrine manner to inhibit proinflammatory cytokine synthesis. ⋯ A transient early rise in IL-4 production was noted in the FFx-LPS group that received exogenous IL-10; however, a subsequent rapid decline was documented. Treatment with anti-IL-10 antibody after FFx injury and septic challenge with LPS is associated with an upregulation of splenocyte IL-4 synthesis, as well as an increase in mortality in this murine model. IL-4 and IL-10 interaction postinjury may profoundly influence monocyte activation, cell-mediated immunity, and the subsequent host immune response to infection.
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Comparative Study
Transthoracic bioimpedance can measure extravascular lung water in acute lung injury.
We used a porcine endotoxemic model of acute lung injury to compare extravascular lung water (EVLW) measured by right transthoracic bioimpedance to postmortem gravimetric EVLW measurements. Adult pigs were randomized into control (N = 5) or endotoxin groups [150 microgram/kg Escherichia coli lipopolysaccharide B for 1 hr followed by 3 hr of resuscitation for a thermodilution cardiac output less than 90% of baseline using either isotonic saline (N = 5) or isooncotic albumin (N = 5)]. Right lung resistance was measured using a novel electrode array and a highly sensitive analyzer and was used to calculate right lung resistivity. ⋯ Using multiple regression analysis, a predictive equation for EVLW based on right lung resistivity, body weight, and mean pulmonary artery pressure was generated (r2 = 0.81; SEE = 0.60; P < 0.0001). These results demonstrate that right lung resistivity measurements can provide a noninvasive estimate of EVLW. In addition, crystalloid may be preferable to colloid for fluid resuscitation in noncardiogenic pulmonary edema.