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C. difficile toxin A increases intestinal permeability and induces Cl- secretion.

Mucosal sheets of guinea pig ileum mounted in Ussing chambers were used to determine effects of highly purified Clostridium difficile toxin A on intestinal structure and barrier function in the absence of recruited neutrophils and blood flow. With the use of standard electrophysiological and morphological techniques, our results indicate that 5 micrograms/ml mucosal toxin A induces substantial alteration in epithelial permeability and in structure of absorptive cells. Transepithelial fluxes of mannitol (3.6 A) and inulin (11.5 A) increased 20-80 min after toxin A exposure (63 +/- 13 vs. 149 +/- 14 and 2.33 +/- 0.43 vs. 7.03 +/- 1.0 nmol.cm-2.h-1 for mannitol and inulin; controls vs. toxin exposed, respectively, both P less than 0.01). Toxin A exposure diminished short-circuit current (153 +/- 8 vs. 77 +/- 6 microA/cm2 for control and toxin exposed, respectively, P less than 0.001), decreased transepithelial electrical resistance (61.6 +/- 3 vs. 50.1 +/- 3.9 omega.cm2 for control and toxin exposed, respectively, P less than 0.05), increased passive permeation of Na+ (19.1 +/- 0.9 vs. 27.4 +/- 0.9 mumol.cm-2.h-1 for control and toxin exposed, respectively), and induced a Cl- secretory response (net flux 3.65 +/- 3.0 vs. -4.62 +/- 2.6 mumol.cm-2.h-1, for control and toxin exposed, respectively, P less than 0.05) over the 2-h experimental time course. Toxin A-induced structural alterations of villus tip absorptive cells were strikingly similar to those induced by the actin-binding agent cytochalasin D. Specifically, cells displayed constricted subjunctional zones, flared microvillus brush borders, condensation of microfilaments in the zone of the perijunctional actomyosin ring, and breakdown of intercellular tight junctions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modelling of intestinal permeability in man to polyethylene glycols (PEG 400 and PEG 1000).

The intestinal permeability barrier was evaluated in four healthy individuals by the 6 h urinary recovery of a mixture of different-sized polyethylene glycols (PEG 400 and PEG 1000) after a liquid meal of probe molecules. The mixture of PEGs contained around 25 different PEG polymers, ranging from about 194 to 1294 dalton in size. Three models were employed to get a condensed formulation of the intestinal barrier, namely a filter function, describing exclusion of molecules due to the molecular weight, and two expressions for ultrafiltration through a pore due to the Stoke-Einstein radius. A factor reflecting unrestricted passage of probe molecules in the size-range used was also included in the mathematical expressions. It was found that a filter function showing half-maximum exclusion at 589-956 daltons (Da) PEG and a pore function yielding a pore-size of 8.0-8.5 A equally well described the intestinal barrier in the four subjects. The results are discussed in relation to structures of the intestinal epithelium that may restrict the passage of molecules.

Capillary Permeability↗

Current concepts in the evaluation, diagnosis and management of acute infectious diarrhea.

Despite recent advances in our understanding of the pathogenesis of enteric diseases, acute infectious diarrhea remains a major cause of morbidity and mortality worldwide. Infection is the most common cause of acute diarrhea. Some causes of infectious diarrhea also result in serious long-term sequelae such as hemolytic uremic syndrome, Guillain-Barré syndrome and malnutrition. A better understanding of bacterial pathogenesis has grown increasingly important because of the emergence of new pathogens and the growing problems of resistance among enteric pathogens and other enteric flora. Non-antimicrobial approaches to therapy have become increasingly important with the emergence of serious antimicrobial resistance, such as vancomycin-resistant enterococcal colonization of the gastrointestinal tract. Finally, new understanding of how intestinal bacteria cause disease is revealing that enteric infections might trigger damage to epithelial cells or the intestinal barrier, or disrupt intestinal barrier and absorptive function (without necessarily causing overt diarrhea); thus, enteric infections might be far more important as emerging causes of malnutrition than has been previously appreciated. Therefore, diarrhea is both a cause and an effect of malnutrition. Treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration. Prevention of enteric illness by virtue of improved hygiene and provision of sanitation and water treatment is impractical in most developing countries, where morbidity and mortality rates are highest. For this reason, development of vaccines against the most important gastrointestinal infections remains a high priority.

Acute Disease↗

Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease.

BACKGROUND/AIMS: No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (Mr>1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse and mild to more advanced stages of liver disease, and to measure the concentration of endotoxins in the plasma, as these compounds derive from the intestinal flora and are suspected to contribute to the development of alcoholic liver disease (ALD). METHODS: The permeability to polyethylene glycol Mr 400, Mr 1500, Mr 4000, and Mr 10,000 and endotoxin plasma concentrations were measured in 54 patients with alcoholic liver disease, 19 of them with cirrhosis, and in 30 non-alcoholic healthy controls. RESULTS: Permeability to polyethylene glycol Mr 400 was found to be unchanged in patients with ALD in comparison to healthy controls, whereas polyethylene glycol Mr 1500 and Mr 4000 were recovered in about twice as high concentrations in the urine of ALD patients (p<0.01). Polyethylene glycol Mr 10,000 was detected significantly less frequently in urine from healthy controls (0/30) than in urine of patients with alcoholic liver disease (20/54, p<0.01). Endotoxin concentrations in the plasma of alcoholics were increased more than 5-fold compared to healthy controls (p<0.01). CONCLUSIONS: The results of this study indicate that alcohol abuse impairs the function of the intestinal barrier, which might enhance the translocation of bacterial toxins, thereby contributing to inflammatory processes in alcoholic liver disease.

Adult↗

Liver abscess following superior mesenteric artery revascularization for acute mesenteric ischemia.

A case of pyogenic liver abscess following successful mesenteric artery revascularization is described in a patient with acute mesenteric ischemia. Prior to revascularization, arteriography confirmed celiac and superior mesenteric artery occlusion. Occurrence of liver abscess is explained on the basis of ischemia impairing the barrier function of the intestinal mucosa, contributing to portal bacteremia that seeds ischemic or necrotic liver. In patients with acute mesenteric ischemia, sequential sonographic examination of the liver following mesenteric revascularization is advocated for early diagnosis of liver abscess if there is clinical evidence of the sepsis.

Acute Disease↗

Gastrointestinal mucosal injury in experimental models of shock, trauma, and sepsis.

BACKGROUND AND METHODS: The mucosa of the GI tract serves as an important barrier limiting the systemic absorption of luminal microbes and microbial products. Two methods commonly used to assess the integrity of the GI mucosal barrier are assessment of the extent of microbial translocation and measurement of mucosal permeability to hydrophilic probes. RESULTS: Studies using these methods have provided convincing evidence that the barrier function of the intestinal mucosa is deranged in numerous animal models of shock, trauma, and sepsis. CONCLUSIONS: Although the mechanisms underlying mucosal injury under these circumstances remain incompletely understood, current evidence suggests that mucosal damage in shock, trauma, and sepsis is likely due to various combinations of intracellular hypoxia due to ischemia, tissue injury caused by reactive oxygen metabolites, the deleterious effects of various lipid mediators (e.g., platelet-activating factor) and/or cytokines (e.g., tumor necrosis factor), and deficient utilization or supply of key nutritional substrates (e.g., glutamine).

Animals↗

Early administration of enteral nutrients in critically ill patients.

Aggressive nutrition intervention has become an essential component in the therapy of critically ill patients. Early provision of enteral nutrients within 24 hours of injury or surgery appears optimal and is associated with benefits such as a reduction in septic complications, a decrease in the hypermetabolic response to severe burn injury, and improved wound healing. Early enteral nutrient administration has a significant impact on preserving gastrointestinal integrity and barrier function and maintaining intestinal immunologic defenses, which may have a role in decreasing infectious outcomes in critically ill patients. Establishing an enteral access becomes a priority with early feeding. Small intestine feeding usually is preferred to gastric nutrient administration, yet some declare biologic superiority with intragastric feedings. The optimal enteral product for use in critically ill patients remains unknown. Key nutrients, such as glutamine, arginine, fiber, and alternative lipids, may have potential benefits and need to be considered when formulating an enteral regimen in this patient population.

Critical Illness↗

Evaluation of a triple sugar test of colonic permeability in humans.

AIM: Conventional dual sugar tests of intestinal permeability assess only the stomach and small intestine. A novel triple sugar method of assessing colonic permeability has recently been described in animals. This utilizes the non-fermented sweetener sucralose, in addition to conventional sugars. It has been postulated that this test enables the simultaneous assessment of small-intestinal and colonic barrier function in humans. The aim of this study was to evaluate the triple sugar test using healthy volunteers and ileostomists. METHODS: Twenty-one healthy volunteers and 18 ileostomists underwent the triple sugar test. After an overnight fast, subjects drank a solution containing lactulose (5 g), rhamnose (1 g) and sucralose (5 g). Urine was collected for 0-5 h and 5-19 h. Urinary sugars were quantified using HPLC, and 5 and 24-h excretion calculated. Nineteen control subjects and 16 ileostomists also underwent a 51Cr-EDTA permeability test. Permeability data were presented as medians (IQR), and differences between groups analysed with Mann-Whitney U-tests. RESULTS: Lactulose excretion and the 5-h lactulose/rhamnose (L/R) ratio were similar in controls and ileostomists [L/R ratio 0.024 (0.022-0.034) vs. 0.025 (0.022-0.035), P = 0.955]. Twenty-four hours excretion of sucralose was significantly higher in control subjects compared with ileostomists [1.41% (1.17-1.68) vs. 0.96% (0.64-1.2), P = 0.003]. The same pattern was seen with 51Cr-EDTA [2.73% (2.06-3.76) vs. 2.06% (1.55-2.71), P = 0.037] and with lactulose [0.52% (0.42-0.60) vs. 0.25% (0.16-0.35), P = 0.002]. CONCLUSIONS: Both sucralose and 51Cr-EDTA underwent significant colonic absorption. A significant amount of lactulose also appeared to be absorbed in the colon. This unexpected finding requires further study.

Adult↗

Interstitial fluid accumulation does not influence oxygen uptake in the rabbit small intestine.

Crystalloid resuscitation increases interstitial fluid volume. Intestinal ischemia and impaired barrier function may contribute to the precipitation of multiple organ failure. Accordingly, the intestine was chosen as target organ to test whether interstitial oedema impairs oxygen extraction by the tissue. The portal vein in anaesthetized rabbits was partially obstructed for 30 min along with an intravenous infusion of 0.9% saline 60-90 ml kg-1 (oedema group, n = 7). Total water content of the small intestine increased from 3.4 ml g-1 dry weight in control (n = 8) to 3.9 ml g-1 in the oedema group (P = 0.049). Small intestinal O2 uptake was calculated from the arteriovenous O2 content and electromagnetic flow measurements in the superior mesenteric artery. Mesenteric flow was reduced stepwise by a snare occluder around the artery. Intestinal oxygenation was monitored indirectly as well, by means of mesenteric venous lactate, arterial base excess and by mucosal pH (pHi) assessed tonometrically. The oxygen extraction ratios were similar in the oedema and control group at similar oxygen supplies. After a 45 min flow reduction to 15% of baseline mesenteric venous lactate and pHi did not differ between the groups. pHi averaged 7.31 and fell to 6.74. Below an intestinal O2 uptake of 2.5 ml min-1, pHi correlated somewhat better with O2 uptake (r = 0.66) than did arterial base excess (r = 0.50). The results indicate that acute elevation of extracellular volume to the extent in the present study, does not impede oxygen uptake in the gut.

Acid-Base Imbalance↗

Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 1: eradication of Helicobacter in the cachexia of idiopathic parkinsonism.

BACKGROUND: Neuronal damage in idiopathic parkinsonism may be in response to ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter is a prime candidate. AIM: To consider the candidature of Helicobacter in parkinsonism with cachexia. METHODS: We explore the relationship between being underweight and inflammatory products in 124 subjects with idiopathic parkinsonism and 195 controls, and present the first case-series evidence of efficacy of Helicobacter eradication, in parkinsonism advanced to the stage of cachexia. RESULTS: Association of a low body mass index with circulating interleukin-6 was specific to parkinsonism (p = .002), unlike that with antibodies against Helicobacter vacuolating-toxin and cytotoxicity-associated gene product (p < .04). Marked reversibility in both cachexia and disability of idiopathic parkinsonism followed Helicobacter heilmannii eradication in one case, Helicobacter pylori eradication in another, follow-up being > or = 3.5 years. The latter presented with postprandial bloating, and persistent nausea: following eradication, radioisotope gastric-emptying returned towards normal, and upper abdominal symptoms regressed. Reversibility of their cachexia/disability contrasts with the outcome of anti-Helicobacter therapy where eradication repeatedly failed (one case), and in non-Helicobacter gastritis (three cases). Anti-parkinsonian medication remained constant. Intestinal absorption and barrier function were normal in all. CONCLUSION: Categorization, according to presence or absence of Helicobacter infection, was a useful therapeutic tool in late idiopathic parkinsonism.

Aged↗

Impaired gut lipid absorptive capacity after trauma-hemorrhage and resuscitation.

Although the barrier function of the intestinal mucosa is impaired after hemorrhage, it remains unclear whether this is associated with a deficit in mucosal function. The aim of this study, therefore, was to determine whether trauma-hemorrhage affects the in vivo lipid absorptive capacity of the gut and, if so, to characterize the uptake process of free fatty acids in isolated enterocytes. To study this, rats were anesthetized, a laparotomy was performed (i.e., trauma was induced), and various blood vessels were cannulated. For in vivo lipid absorption, the main intestinal lymph vessel was cannulated and a jejunostomy feeding tube was inserted. The animals were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of shed blood volume was returned in the form of Ringer lactate. They were then resuscitated with four times the volume of maximal bleed out with Ringer lactate. The in vivo and in vitro lipid absorptive capacities were assessed by measuring lymph triglyceride output after a fat load and by determining the linoleic acid uptake rates on isolated enterocytes, respectively. The results show that the in vivo lipid absorption capacity of the gut is severely depressed after trauma-hemorrhage and resuscitation. Similarly, in enterocytes isolated from hemorrhaged rats, fatty acid uptake capacity, as reflected by the decreased maximal uptake rates, was significantly reduced: 1.2 +/- 0.2 and 2.6 +/- 0.6 nmol.min-1 x 10(6) cells-1 for hemorrhaged and sham, respectively. Thus gut lipid absorptive function is depressed after trauma-hemorrhage and resuscitation, which is at least partially due to the depressed uptake mechanism of the enterocyte.

Animals↗

Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine.

AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P <0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA,which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination.

Acarbose↗

[Influence on the concentration of plasma endotoxin by inhibition of complement activation in traumatic hemorrhagic shock rats].

OBJECTIVE: To investigate the influence on the concentration of plasma endotoxin by inhibition of complement activation in traumatic hemorrhagic shock rats. METHODS: Eighty male SD rats were randomly divided into two groups: control and cobra venom factor (CVF) treatment groups. The hemorrhagic shock induced by trauma was replicated in both groups. The animals were killed preshock and at 1, 6, and 24 hours postresuscitation. Twenty-four hours before hemorrhage, rats were given a mainline dose of either 50 microg/kg CVF or an equal volume of saline solution. The plasma and serum samples were collected at each time point to determine the concentration of endotoxin, the activity of CH50 and diamine oxidase (DAO), and the level of tumor necrosis factor (TNF-alpha) at various time points in two groups. RESULTS: Compared with preshock in control group, serum CH50 levels were decreased promptly at 1 hour postresuscitation. Markedly elevation of the levels of endotoxin and TNF-alpha in blood were found at early time after resuscitation, and they were come rapidly back to the basic level at 6 and 24 hours phase. The activity of DAO in blood was increased significantly at 1 and 6 hours after resuscitation and declined promptly at 24 hours. Compared with the control group, significantly decline of the levels of endotoxin, TNF-alpha and DAO at the various time points after resuscitation were also found in the CVF group. The levels of CH50 in CVF group were always less than 5% during the experiment. CONCLUSION: In traumatic hemorrhagic shock rats CVF pretreatment could decline plasma endotoxin levels by preventing the injury of intestine and gut barrier function, decrease endotoxin translocation and reduce plasma endotoxin levels.

Animals↗

[The multiple organ failure syndrome--its pathophysiology and treatment].

Polyorganic deficiency syndrome (PODS) is a generalized response to the effect of a variety of agents hardly lending itself to control, becoming manifest with rapid proliferation within the body. The issues discussed include: epidemiology with a special reference to panendothelial trauma to pulmonary and other systems with impairment of oxygen utilization by the cells, microcirculation disorders, mediators, ARDS development, disturbed barrier function of the intestinal mucosa, enhanced glutamine consumption with ensuing villous atrophy. Symptoms presented by various organs, treatment consisting in block of stimulation and block of mediators, as well as selective decontamination and adequate diet are also dealt with. Against the background outlined above the prognostic point rating system (the so-called score rating) of PODS with simultaneous application of the APACHE III rating system are evaluated. Age-related factors and number of organs involved are likewise considered.

Humans↗

[Administration of glutamine and its dipeptides in parenteral nutrition. Which patients are candidates?].

Despite the fact that glutamine is not considered to be an essential amino acid, it is the amino acid found in the greatest concentration both in plasma (26%) as in skeletal muscle (75%). These levels may decrease in post-operative, trauma, or critical patients. Glutamine performs many functions in which its demand may be increased, such as: it is a precursor of the synthesis of nucleotides; it is an activator of the protein synthesis and at the same time it inhibits the degradation; it is an activator of glycogen synthesis; it is a metabolic substrate for rapidly replicating cells; it is an energy source for the enterocyte which is so important for maintaining the integrity and the function of the intestinal barrier, and the consumption thereof may be increased under conditions of stress. The administration of glutamine intravenously leads to two physical-chemical problems; the first is its low solubility in water; at 20 degrees C this is only 36 g/l, and the second problem is its low chemical stability in an aqueous solution at 22-24 degrees C, this being 11 days. This problem has led the industry to research two dipeptides of glutamine; L-alanyl-glutamine, and L-glycyl L-glutamine, both of which are much more soluble and much more stable. At present there is still a controversy regarding the dosage of glutamine and its dipeptides, with the dose being 0.19-0.29 g/kg/day of L-glutamine or its dipeptide forms, in surgical post-operative periods or to prevent bacterial translocation, and in patients who are candidates for bone marrow transplants, the administered dose has been 0.37-0.57 g/kg/day. The purpose of this study is to review the existing bibliography regarding the efficacy of L-glutamine or its dipeptides in four possible indications for its application in the daily clinical practice, such as: a) In post-operative surgical patients of major or medium surgery, glutamine or its dipeptides reduces the losses of muscular glutamine and its catabolism, showing a less negative nitrogen balance. b) Whether it avoids bacterial translocation. c) Whether it favors the response of the immunological system. d) Whether in patients who are candidates for bone marrow transplants this decreases the side effects due to chemotherapy and radiotherapy such as mucositis, or whether it decreases the number of days of neutrophil recovery. At present, on the European market there are two commercially available brands of glutamine dipeptides: Dipeptiven, by Fresenius Laboratories, Germany. A 100 ml vial which corresponds to 20 g of L-alanyl L-glutamine (8.2 g of alanine + 13.46 g of L-glutamine). This is added to the standard amino acid solution. Glamin, Pharmacia and Upjohn Laboratory, Sweden. This is an amino acid solution with 13.4% essential and non-essential amino acids which are equivalent to 22.4 g of nitrogen/l, and which contain 30.27 g L-glycyl-L-glutamine (10.27 g of glycine + 20 g of L-glutamine).

Bone Marrow Transplantation↗

Effects of nucleosides and a nucleotide mixture on gut mucosal barrier function on parenteral nutrition in rats.

BACKGROUND: We have previously reported that the addition of nucleosides and a nucleotide mixture (OG-VI) to total parenteral nutrition (TPN) prevents TPN-induced intestinal mucosal atrophy and results in increased intestinal cathepsin activities under TPN. The aims of the present study are to examine the effects of OG-VI on mucosal barrier functions and to clarify whether the intestinal cathepsins can be used as a new marker of mucosal barrier function. METHODS: Male Wistar rats were divided into three groups: FED (food ad libitum), TPN (a standard TPN solution), and OG (OG-VI in addition to the TPN solution). Mucosal barrier functions were analyzed by the lactulose/mannitol (L/M) test, mucosal ZO-1 messenger RNA level, and electron micrographs in the gut. Intestinal cathepsin B, H, and L activities were also measured. RESULTS: The L/M ratio for TPN was much higher than that for FED. Only lactulose excretion was significantly reduced by OG-VI. The intercellular spaces of the mucosal cells for TPN were significantly wider than those for FED, but were reduced in size by the addition of OG-VI. All cathepsin activities of the ileum were higher for TPN than for FED, whereas OG showed no increase. CONCLUSION: OG-VI contributes to the improvement of gut mucosal barrier function. Intestinal cathepsin activities can be used as a new marker of mucosal barrier function.

Animals↗

Polyamines are necessary for synthesis and stability of occludin protein in intestinal epithelial cells.

Occludin is an integral membrane protein that forms the sealing element of tight junctions and is critical for epithelial barrier function. Polyamines are implicated in multiple signaling pathways driving different biological functions of intestinal epithelial cells (IEC). The present study determined whether polyamines are involved in expression of occludin and play a role in intestinal epithelial barrier function. Studies were conducted in stable Cdx2-transfected IEC-6 cells (IEC-Cdx2L1) associated with a highly differentiated phenotype. Polyamine depletion by alpha-difluoromethylornithine (DFMO) decreased levels of occludin protein but failed to affect expression of its mRNA. Other tight junction proteins, zonula occludens (ZO)-1, ZO-2, claudin-2, and claudin-3, were also decreased in polyamine-deficient cells. Decreased levels of tight junction proteins in DFMO-treated cells were associated with dysfunction of the epithelial barrier, which was overcome by exogenous polyamine spermidine. Decreased levels of occludin in polyamine-deficient cells was not due to the reduction of intracellular-free Ca(2+) concentration ([Ca(2+)](cyt)), because either increased or decreased [Ca(2+)](cyt) did not alter levels of occludin in the presence or absence of polyamines. The level of newly synthesized occludin protein was decreased by approximately 70% following polyamine depletion, whereas its protein half-life was reduced from approximately 120 min in control cells to approximately 75 min in polyamine-deficient cells. These findings indicate that polyamines are necessary for the synthesis and stability of occludin protein and that polyamine depletion disrupts the epithelial barrier function, at least partially, by decreasing occludin.

CDX2 Transcription Factor↗

Milrinone modulates endotoxemia, systemic inflammation, and subsequent acute phase response after cardiopulmonary bypass (CPB).

BACKGROUND: Compromised splanchnic perfusion and the resulting intestinal mucosal injury leads to a decreased mucosal barrier function, which allows translocation of intestinal flora and endotoxemia. The authors evaluated the effects of milrinone on splanchnic oxygenation, systemic inflammation, and the subsequent acute-phase response in patients undergoing coronary artery bypass grafting. METHODS: This open, placebo-controlled randomized clinical study enrolled 22 adult patients in two groups. Before induction of anesthesia, baseline values were obtained and patients were randomized to receive milrinone (30 microg/kg bolus administered progressively in 10 min, followed by a continuous infusion of 0.5 microg x kg(-1) x min(-1)) or saline. The following parameters were determined: hemodynamics; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; intramucosal pH (pHi); and mixed and hepatic venous plasma concentrations of endotoxin, interleukin 6, serum amyloid A, and C-reactive protein. RESULTS: Milrinone did not prevent gastrointestinal acidosis as measured by pHi, but its perioperative administration resulted in significantly higher pHi levels compared with control. Venous and hepatic venous endotoxin and the interleukin 6 concentration were reduced significantly in the milrinone group. Serum amyloid A values were attenuated in the milrinone group 24 h after surgery. No significant differences could be seen in routinely measured oxygen transport-derived variables. CONCLUSIONS: Perioperative administration of low-dose milrinone may have antiinflammatory properties and may improve splanchnic perfusion in otherwise healthy patients undergoing routine coronary artery bypass grafting.

Acute-Phase Reaction↗