Abolition of 'Tryptic Enteritis' in the Shocked Dog

Bounous, G; Brown, Ralph S.; Mulder, David S.; Hampson, Lynne; Gurd, Fraser N.

doi:10.1001/archsurg.1965.01320150001001

Cited by 75 publications

(6 citation statements)

References 2 publications

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“…In fact, our findings that intestinal perfusion with vehicle (Ringers lactate) displayed a modest but statistically significant protective effect on lung injury indicates that washing proteases as well as other potentially active factors out of the intestine limits T/HS-induced lung injury. Even two decades before the recent work of SchmidSchonbein (12,13,17,18), the pancreas had been proposed as playing an important pathologic role in the organ failure observed after hemorrhagic or traumatic shock (19)(20)(21)(22)(23)(24). For example, the work of Lefer et al implicated the pancreas as the source of myocardial depressant factor (22), whereas Bounous et al (23) showed that the magnitude of ischemic gut injury was mitigated by pancreatic protease inhibition or pancreatic duct ligation.…”

Section: Fig 1 Linear Regression Analysis Demonstrates a Direct Relmentioning

confidence: 99%

Serine Proteases Are Involved in the Pathogenesis of Trauma-Hemorrhagic Shock-Induced Gut and Lung Injury

Deitch

Shi²,

Lu³

et al. 2003

Shock

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The objective of this work was to test the hypothesis that Intraluminal serine proteases are involved in trauma-hemorrhagic shock (T/HS)-induced intestinal and lung injury. Male Sprague-Dawley rats were administrated the serine protease inhibitor (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfate, Nafamostat) either intraluminally into the gut or intravenously after a laparotomy (trauma) and then subjected to 90 min of hemorrhagic shock (T/HS) or sham shock (T/SS). Intestinal and lung injury was assessed at 3 h after resuscitation with Ringer's lactate solution. In a second set of experiments, mesenteric lymph was collected from the groups of rats subjected to T/HS or T/SS and its ability to activate normal neutrophils was tested. Lung permeability, pulmonary myeloperoxidase levels, and the bronchoalveolar lavage fluid protein to plasma protein ratio were increased after T/HS but were significantly decreased in the T/HS rats receiving intraluminal (P < 0.05), but not intravenous, nafamostat. Likewise, T/HS-induced intestinal villus injury was less in the nafamostat-treated shock rats (P < 0.05). Last, the ability of T/HS mesenteric lymph to increase PMN CD11b expression or prime neutrophils for an augmented respiratory burst was significantly reduced by the intraluminal administration of nafamostat. Because intraluminal nafamostat reduced T/HS-induced gut and lung injury as well as the neutrophil activating ability of intestinal T/HS lymph, the presence of serine proteases in the ischemic gut may play an important role in T/HS-induced gut and hence lung injury.

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Section: Fig 1 Linear Regression Analysis Demonstrates a Direct Relmentioning

confidence: 99%

Serine Proteases Are Involved in the Pathogenesis of Trauma-Hemorrhagic Shock-Induced Gut and Lung Injury

Deitch

Shi²,

Lu³

et al. 2003

Shock

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“…The intestine plays a central role in shock and has been hypothesized to be a primary source of inflammatory mediators (1,2,9,11,26,32). Trauma, sepsis, burns, radiation, and other insults may cause ischemia in the gut and increased permeability of the intestinal mucosal layer (5,37,45).…”

mentioning

confidence: 99%

The intestine as source of cytotoxic mediators in shock: free fatty acids and degradation of lipid-binding proteins

Penn¹,

Schmid‐Schönbein²

2008

American Journal of Physiology-Heart and Circulatory Physiology

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Shock and multiple organ failure remain primary causes of late-stage morbidity and mortality in victims of trauma. During shock, the intestine is subject to extensive cell death and is the source of inflammatory factors that cause multiorgan failure. We (34) showed previously that ischemic, but not nonischemic, small intestines and pancreatic protease digested homogenates of normal small intestine can generate cytotoxic factors capable of killing naive cells within minutes. Using chloroform/methanol separation of rat small intestine homogenates into lipid fractions and aqueous and sedimented protein fractions and measuring cell death caused by those fractions, we found that the cytotoxic factors are lipid in nature. Recombining the lipid fraction with protein fractions prevented cell death, except when homogenates were protease digested. Using a fluorescent substrate, we found high levels of lipase activity in intestinal homogenates and cytotoxic levels of free fatty acids. Addition of albumin, a lipid binding protein, prevented cell death, unless the albumin was previously digested with protease. Homogenization of intestinal wall in the presence of the lipase inhibitor orlistat prevented cell death after protease digestion. In vivo, orlistat plus the protease inhibitor aprotinin, administered to the intestinal lumen, significantly improved survival time compared with saline in a splanchnic arterial occlusion model of shock. These results indicate that major cytotoxic mediators derived from an intestine under in vitro conditions are free fatty acids. Breakdown of free fatty acid binding proteins by proteases causes release of free fatty acids to act as powerful cytotoxic mediators.

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“…Many attempts have been made to decrease the mortality of acute intestinal ischaemia but, although some successes have been claimed in the experimental animal, there has been little improvement in the human situation (Boley et al, 1973;Haddad, 1974). Bounos et al (1965) have shown that ischaemia of the small intestine causes necrosis of the bowel which begins at the tips of the villi and gradually progresses toward the serosal surface. Chiu et al (1970) instilled 10% glucose into ischaemic sacs of canine small intestine and not only prevented further necrosis of the mucosa, but possibly also reversed established damage.…”

Section: Necropsy Resultsmentioning

confidence: 99%

Effect of intraluminal oxygen on experimental ischaemia of the intestine.

Shute¹

1976

Gut

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SUMMARY The small bowel of 44 rats has been made ischaemic for 120 minutes by occluding the superior mesenteric artery. Gaseous oxygen was introduced into the small bowel lumen of 18 of the rats, and gaseous nitrogen into the bowel lumen of a further eight, 30 minutes after the start of the ischaemia. The mortality rate of thecontrolgroup of 18 rats was 89 %, significantlyhigher than the 39 % mortality of the oxygen-treated rats (p < 0 005). None of the eight rats treated with intraluminal nitrogen survived. Histological changes caused by ischaemia were much reduced in the intestine of the oxygen treated rats.

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Abolition of 'Tryptic Enteritis' in the Shocked Dog

Cited by 75 publications

References 2 publications

Serine Proteases Are Involved in the Pathogenesis of Trauma-Hemorrhagic Shock-Induced Gut and Lung Injury

Serine Proteases Are Involved in the Pathogenesis of Trauma-Hemorrhagic Shock-Induced Gut and Lung Injury

The intestine as source of cytotoxic mediators in shock: free fatty acids and degradation of lipid-binding proteins

Effect of intraluminal oxygen on experimental ischaemia of the intestine.

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