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The studies of the mechanisms by which trauma-hemorrhagic shock leads to gut injury and dysfunction have largely ignored the nonbacterial factors contained within the lumen of the intestine. Yet, there is increasing evidence suggesting that intraluminal pancreatic proteases may be involved in this process. Thus, we tested the hypothesis that pancreatic proteases are necessary for the trauma-hemorrhagic shock-induced gut injury and the production of biologically active mesenteric lymph by determining the extent to which pancreatic duct ligation (PDL) would limit gut injury and mesenteric lymph bioactivity. To assess the effect of PDL on gut injury and dysfunction gut morphology, the mucus layer structure and the gut permeability were measured in the following four groups of male rats subjected to laparotomy (trauma) and hemorrhagic shock (pressure, 30 mmHg for 90 min): (1) rats subjected to trauma plus sham-shock (T/SS), (2) T/SS rats undergoing PDL (T/SS + PDL), (3) rats subjected to trauma and hemorrhagic shock (T/HS), and (4) rats subjected to T/HS + PDL. The ability of mesenteric lymph from these four rat groups to kill endothelial cells and activate neutrophils was tested in vitro. The PDL did not affect any of the parameters studied because there were no differences between the T/SS and the T/SS + PDL groups. However, PDL protected the gut from injury and dysfunction because PDL significantly abrogated T/HS-induced mucosal villous injury, loss of the intestinal mucus layer, and gut permeability. Likewise, PDL totally reversed the endothelial cell cytotoxic activity of T/HS lymph and reduced the ability of T/HS lymph to prime naive neutrophils for an augmented respiratory burst. Thus, it seems that intraluminal pancreatic proteases are necessary for the T/HS-induced gut injury and the production of bioactive mesenteric lymph.

The goal of this study was to test the hypothesis that factors released from the gut and carried in the mesenteric lymph contribute to mortality in a lethal gut I/R model. To test this hypothesis, a lethal splanchnic artery occlusion (SAO) shock model was used in male Sprague-Dawley rats. In the first set of experiments, ligation of the mesenteric lymph duct (LDL), which prevents gut-derived factors carried in the intestinal lymphatics from reaching the systemic circulation, significantly improved 24-h survival after a 20-min SAO insult (0% vs. 60% survival; P < 0.05). This increase in survival in the LDL-treated rats was associated with a blunted hypotensive response. Because increased iNOS-induced NO levels have been implicated in SAO-induced shock, we measured plasma nitrite/nitrate levels and liver iNOS protein levels in a second group of animals. Ligation of the mesenteric lymph duct significantly abrogated the SAO-induced increase in plasma nitrite/nitrate levels and the induction of hepatic iNOS (P < 0.05). In an additional series of studies, we documented that LDL increased not only 24-h but also long-term 7-day survival. During the course of these studies, we made the unexpected finding that Sprague-Dawley rats from different animal vendors had differential resistance to SAO, and that the time of the year that the experiments were carried out also influenced the results. Nonetheless, in conclusion, these studies support the hypothesis that factors carried in the mesenteric lymph significantly contribute to the development of irreversible shock after SAO.

The idea of acute care surgery conjures up visions of a spectrum of patients with diverse problems that cross many specialties. However, prolonged starvation or malnutrition worsens the outcome of all patients regardless of their diseases, and the development of acute malnutrition is especially common in the critically ill. Consequently, optimal nutritional support has become a key therapeutic aim in trauma patients and patients requiring acute care surgery. Recognition of the importance of nutritional therapy has led to a search for improved methods of nutritional support that promote wound healing and optimize host immune defenses. Unfortunately, impaired wound healing resulting in anastamotic leaks and wound-related problems as well as the development of septic complications and multiple organ failure still occurs.Nonetheless, one potential way of reducing wound failure, muscle wasting, and sepsis-related morbidity and mortality is by limiting or preventing the adverse consequences of uncontrolled inflammatory-mediated hypermetabolism. Although immune and inflammatory dysfunction in these patients are multifactorial, the nutritional status of the patient clearly plays a major role in the ability to ward off an infectious challenge, and recent evidence suggests that the immune and inflammatory systems can be modulated by the use of specific means of nutritional support. Thus, this chapter focuses on nutritional support for the high-risk patient and emphasizes evidenced-based practice management (Figure 7.1). Metabolism, Nutrition, and InfectionUnderstanding the basic biology of the metabolic response to injury and surgery as well as the role of nutrition in modulating this response is important, because the metabolic status of the patient influences muscle strength, various aspects of host defense against invading organisms, and wound healing. Although this section focuses primarily on the hypermetabolic response, the increased physiologic demands placed on the cardiac, pulmonary, renal, and other organ systems can complicate nutritional support and are noted.The hypermetabolic response that occurs after a trauma, shock, or sepsis is characterized by a hyperdynamic circulatory state, fever, weight loss, and progressive skeletal muscle wasting, and it can remain elevated for weeks after healing is complete. The magnitude of the response parallels the extent of the injury/stress and 7

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