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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A great deal has been learned about the pathophysiologic condition of hemorrhagic shock. The response of the hormonal and inflammatory mediator systems in patients in hemorrhagic shock appears to represent a distinct set of responses different from those of other forms of shock. The classic neuroendocrine response to hemorrhage attempts to maintain perfusion to the heart and brain, often at the expense of other organ systems. This intense vasoconstriction occurs via central mechanisms. The response of the peripheral microcirculation is driven by local tissue hypoperfusion that results in vasodilation in the ischemic tissue bed. Activation of the systemic inflammatory response by hemorrhage and tissue injury is an important component of the pathophysiologic condition of hemorrhagic shock. Activators of this systemic inflammatory response include ischemia/reperfusion injury and neutrophil activation. Capillary "no-flow" with prolonged ischemia and "no-reflow" with reperfusion may initiate neutrophil activation in patients in hemorrhagic shock. The mechanisms that lead to decompensated and irreversible hemorrhagic shock include (1) "arteriolar hyposensitivity" as manifested by progressive arteriolar vasodilation and decreased responsiveness of the microcirculation to alpha-agonists, and (2) cellular injury and activation of both proinflammatory and counterinflammatory mechanisms. These changes represent a failure of the microcirculation. Redistribution of cardiac output and persistent gut ischemia after adequate resuscitation may also contribute to the development of irreversible hemorrhagic shock. Treatment of hemorrhagic shock includes rapid operative resuscitation to limit activation of the mediator systems and abort the microcirculatory changes that result from hemorrhagic shock. Volume resuscitation and control of hemorrhage, should occur simultaneously. The end point in volume resuscitation of hemorrhagic shock must be maintenance of organ system and cellular function. Whether we use adequate urine output, correction of lactic acidemia, optimization of oxygen delivery, or oxygen consumption as our specific goal, the general objective is to provide adequate crystalloid solution and packed red blood cells to achieve and maintain normal organ and cellular perfusion and function.
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PMID:Hemorrhagic shock. 758 44

Intestinal ischemia is characterized by rapid early inhibition of absorptive function and the appearance of net secretion, although why active secretion persists in the setting of a mucosal energy deficit is unknown. The cryptlike epithelial line T84, a well-characterized model of intestinal Cl- secretion, develops a prominent increase in short-circuit current (Isc, indicative of active Cl- transport) in response to "hypoxia" induced by metabolic inhibitors. The increased Isc is associated with the initial decrease in monolayer ATP content. The Isc is transient and disappears with progressive energy depletion, although graded degrees of ATP depletion induce a more sustained Isc response. Chromatographic analysis and secretory bioassays show that the Isc response to metabolic inhibitors is related to the endogenous release of adenosine into the extracellular space in quantities sufficient to interact locally with stimulatory adenosine receptors. Unlike its classical role as a metabolic feedback inhibitor, adenosine appears to function as an autocrine "feed-forward" activator of active intestinal Cl- secretion. These studies suggest a novel role for adenosine in the conversion of the gut from an absorptive to a secretory organ during ischemic stress, thus contributing to the initial diarrheal manifestation of intestinal ischemia.
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PMID:Activation of Cl secretion during chemical hypoxia by endogenous release of adenosine in intestinal epithelial monolayers. 761 80

Gut ischemia/reperfusion (I/R) provokes lung injury via a mechanism that involves neutrophils [polymorphonuclear neutrophils (PMNs)]. CD11b/CD18 (alpha mB2) is the integrin receptor on PMNs critical for adhesion-dependent oxidative burst. The purpose of this study was to investigate the mechanistic role of CD11b in the process of gut I/R-induced lung injury. Sprague-Dawley rats underwent 45 minutes of superior mesenteric artery (SMA) occlusion with and without CD11b monoclonal antibody treatment (IB6) (1 mg/kg, i.v.), before SMA clamping. At 2-hour reperfusion, PMN presence in tissue was quantitated by myeloperoxidase activity and circulating PMN priming determined by the difference in superoxide production with and without N-formyl-methionyl-leucyl-phenylalanine, whereas lung leak was assessed by 125I-albumin lung/blood ratio. In sum, CD11b blockade prevented gut I/R-induced lung leak, but did not attenuate gut I/R-induced PMN priming or tissue PMN accumulation. In conclusion, gut I/R promotes PMN priming and PMN adhesion in both local and distant beds via receptors other than CD11b, but this B2 integrin receptor is critical for PMN-mediated endothelial injury.
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PMID:CD11b blockade prevents lung injury despite neutrophil priming after gut ischemia/reperfusion. 763 6

The overall goal of this study was to compare the effects of systemic hypotension (hemorrhagic shock) versus local gut ischemia (superior mesenteric artery (SMA) occlusion) on cytokine production and bacteria/endotoxin translocation. Sham or actual SMA occlusion led to an increase in tumor necrosis factor (TNF), which was greatest at the end of the occlusion period, while the IL-6 response peaked 3 h post-SMA occlusion. The TNF and IL-6 response after hemorrhagic shock differed from that observed after SMA occlusion in that the peak response occurred later and was of lower magnitude (p < .05). Although the animals subjected to SMA occlusion had a significantly increased incidence of bacterial translocation to both the mesenteric lymph nodes and systemic organs compared to rats subjected to hemorrhagic shock, in neither group was the blood level of endotoxin elevated and there was no association between bacterial translocation and cytokine levels. These results suggest that different models of intestinal ischemia have different cytokine profiles and that the early TNF response associated with SMA occlusion model is primarily due to the laparotomy.
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PMID:Comparison of plasma cytokine levels in rats subjected to superior mesenteric artery occlusion or hemorrhagic shock. 764 38

Endogenous inflammatory cytokines may function as mediators in the development of remote organ damage in response to local ischemic insult. This study was designed to (a) explore the potential role of tumor necrosis factor (TNF) formation in the pathogenesis of systemic tissue injury, (b) determine the relationship between induction of TNF and gut-derived endotoxemia and/or bacterial translocation, and (c) evaluate the protective effect of anti-TNF monoclonal antibody (MoAb) for vital organs following intestinal ischemia-reperfusion in rats. Animals were subjected to superior mesenteric artery occlusion (SMAO) for 45 min. Systemic plasma TNF levels increased rapidly after the onset of reperfusion, reaching a peak value 2 h later (P < 0.01). TNF elevation was found to be associated with gut origin endotoxemia, where the maximal TNF levels occurred approximately 2 h after the initial appearance of endotoxin in portal vein. Prophylactic treatment with anti-TNF MoAb markedly blunted the elevation in plasma TNF levels and afforded protection from the development of hypotension, vital organs dysfunction, and metabolic acidosis. Significant improvement in 48-h survival rate was observed by administration of anti-TNF MoAb prior to inducing ischemia (P = 0.007). These findings suggest that intestinal ischemia-reperfusion could result in TNF production, which may play a key role in mediating subsequent septic response and systemic tissue injury. It seems likely that passage of endotoxin and bacteria from the gut can be responsible for the TNF formation
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PMID:The potential etiologic role of tumor necrosis factor in mediating multiple organ dysfunction in rats following intestinal ischemia-reperfusion injury. 765 69

Small bowel transplantation may eventually become the definitive solution for those patients who suffer from irreversible intestinal failure and that currently depend on parenteral nutrition for survival. Microsurgical transplantation models in rats are widely used for the application of a great variety of immunological and physiological tests. Herein we report our experience after 30 intestinal harvestings and 12 intestinal transplantations in rats. The following criteria were established to assess the surgical procedures: operative time (harvesting and back table, cold ischemic time and warm ischemic time), vascular and intestinal complications and gut histology before and after transplantation. Average time for the donor surgery (harvesting and back table) was 97.19 min. Average warm ischemic time (includes vascular anastomoses) was 115 min. Histological assessment after 3, 4 and 5 hours of cold ischemia (lactated Ringer's solution with 2.4% mannitol at 4 degrees C) showed only mild ischemic changes. Two thrombotic complications were observed: one at the site of the portalcava anastomosis and one at the aortic suture. Hypovolemic shock was the most common cause of death (9/12) and there was no survival beyond 48 hours. Post-transplantation gut histology showed moderate ischemic injury. We conclude that the harvesting technique, as well as the preservation method used are adequate to obtain grafts in a fast and reliable fashion. However, the number of rats transplanted in this experience do not permit statistical analysis of morbidity and mortality at the present time.
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PMID:[Small intestine transplantation. Experimental microsurgical model in rats]. 766 Jul 28

Histopathologic alterations in the intestinal mucosa after ischemic injury have been extensively described in the literature, but these descriptions have primarily been qualitative in nature. The purpose of this study was twofold: (1) to establish parameters obtained by computerized digital image analysis that would be useful in identifying ischemic injury, and (2) to use these parameters to identify the critical period of intestinal ischemia producing measurable histopathologic change. Seventy male Sprague-Dawley rats weighing 80 to 150 g underwent various times of gut ischemic injury by vascular occlusion of the superior mesenteric artery and vein with a microaneurysm clamp. The clamp times were 0, 1, 20, 30, 40, 50, 60, 70, 80, and 90 minutes. Histological sections of the terminal ileum were quantitatively analyzed using Jandel Scientific's computerized morphometric image analysis system. Parameters studied were surface index (SI, surface length per linear unit of mucosa), average villous thickness (AVT), average villous height (AVH), and the number of villous cells/100 microns length (VC). Ischemic times of 1, 20, 30, and 40 minutes produced no measurable injury as compared with baseline (P[40 minutes versus baseline] = SI, .60; AVT, .84; AVH, .93; VC, .09). At 50 minutes, SI and AVH showed a measurable change from baseline (P[50 minutes versus baseline] = SI, .01; AVH, .02). Sixty minutes of ischemic time produced measurable change in all parameters (P[60 minutes versus baseline] = SI, .007; AVT, .001; AVH, .002; VC, .007).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Computer analyzed histology of ischemic injury to the gut. 766 20

Although routine cardiac surgical procedures are now performed with low rates of mortality and relatively low rates of morbidity, certain categories of patients continue to present a major challenge. Patients who have reoperations and those with active infective endocarditis represent high-risk categories. The pathophysiologic mechanisms involved in such patients include impaired left ventricular function and low cardiac output, sepsis, endotoxemia, and gut permeability, and impaired hemostasis. Although these mechanisms are distinct, they do interrelate. Low cardiac output and imperfect systemic perfusion during and after cardiopulmonary bypass are known to induce splanchnic ischemia with altered permeability of the gut mucosal barrier to gut contents, including endotoxin. The systemic inflammatory response, triggered by contact activation of factor XII, produces functional disturbance in vital organs, notably the brain and lung. In addition, factor XII activation induces disordered hemostasis, which is related to increased fibrinolysis and a possible disturbance in platelet function. Measures to modify these mechanisms and improve outcome in high-risk patients include pulsatile perfusion during cardiopulmonary bypass and aprotinin therapy to modify the inflammatory response and prevent the disorder in hemostasis. Clinical experience with high-dose aprotinin therapy in patients who have reoperations and active endocarditis has demonstrated a very high level of efficacy in reducing blood loss and blood/blood product transfusion requirements. The potential role of aprotinin in stabilizing the microcirculation and modifying the systemic inflammatory response requires further study and may prove to be a major contribution to improved outcome in high-risk patients.
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PMID:Improved outcome for seriously ill open heart surgery patients: focus on reoperation and endocarditis. 768 Feb 32

Nitric oxide (NO.) plays a central role in the Physioliology of the gastrointestinal tract and its response to critical illness. Potential sources of NO. in the gut include: intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neural plexus), resident and/or infiltrating leukocytes (neutrophils, monocytes), reduction of luminal gastric nitrate, and denitrification by commensal anaerobes. The brain and endothelial isoforms of nitric oxide synthase are expressed under resting conditions, whereas inflammatory stimuli are required for the induction of the inducible type. Under resting conditions, mucosal perfusion is regulated by NO. derived from the vascular endothelium of the mesenteric bed. During inflammation, excessive NO. production from the inducible synthase may contribute to mucosal hyperemia. Coordination of peristalsis and sphincteric action is mediated by the release of NO., which acts as the principal neurotransmitter of the nonadrenergic, noncholinergic enteric nervous system. Alterations in bowel motility, such as ileus, result from excessive concentrations of NO. generated during endotoxicosis and inflammatory bowel disease. The role of NO. in the regulation of salt and water secretion is poorly understood. Endotoxin-induced inhibition of gastric acid secretion appears to be mediated by the action of NO. on parietal cells. NO. may protect the gastrointestinal mucosa from a variety of stimuli (caustic ingestion, ischemia, ischemia/reperfusion injury, early endotoxic shock) by maintaining mucosal perfusion, inhibiting neutrophil adhesion to mesenteric endothelium, blocking platelet adhesion, and preventing mast cell activation. Excessive NO., however, may directly injure the mucosa. Barrier function of the intestinal mucosa is protected by NO. in the early stages of injury, when neutrophil adhesion, ischemia, and mast cell activation are relevant. Inhibition of NO. synthesis ameliorates barrier dysfunction during more advanced stages of inflammation, when activation of inducible NOS yields toxic concentrations of NO.. At high concentrations, NO. disrupts the actin cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and produces a hyperpermeable state. Selective inhibition of the inducible isoform of NOS and maintenance of the constitutive types may be therapeutic.
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PMID:Nitric oxide in the gut. 770 93

Neutrophils have been identified to play a major role in ischemia/reperfusion injury through several mechanisms. Neutrophil migration into reperfused gut may reduce bacterial translocation, but may also enhance the reperfusion injury. Ethanol ingestion impairs cutaneous chemotaxis, but its effects on neutrophil migration to postischemic small bowel are unknown. This study investigates the effects of ethanol on small bowel accumulation of neutrophils after ischemia/reperfusion. Ninety-five rats were divided into five groups; normal control, sham operation, ethanol-sham, ischemia, and ethanol-ischemia groups. Ethanol was given once acutely by gavage (3 g/kg, 20% solution) to the animals in the ethanol-sham and the ethanol-ischemia groups 4 hr before ischemic injury. Ischemia was produced for 1 hr by placing a vessel loop around the superior mesenteric vessels. After 1 hr, 87% of animals had gut ischemia and the loop was removed. Three hours later the small bowel was examined for necrosis and the reperfused viable small bowel was extirpated for measurement of neutrophil infiltration by colorimetric assay for myeloperoxidase (MPO), an enzyme restricted to neutrophils. Both ethanol and ischemia/reperfusion produced significant independent increase in the MPO activity. When ethanol was given prior to ischemia, the MPO activity was further increased by statistically significant margin. The present study demonstrated that ethanol enhanced the effects of gut ischemia/reperfusion injury on PMN accumulation into the intestinal wall. These observations suggest that ethanol may potentiate ischemic injury to the gut and lead to increased problems when gut blood flow is significantly impaired.
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PMID:Ethanol ingestion potentiates PMN migration into small intestine after ischemia. 772 15


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