Intestinal Oxygen Consumption Research Articles

A seed-like hydrogel with metabolic cascade microbiota for oral treatment of liver failure

Liver failure is a fatal disease with a mortality rate of 80%. The only access to treat liver failure is invasive operation, which is restricted by limited donor sources or high costs. Thus, non-invasive medication for liver failure is urgently needed. Herein, we tried the first attempt to design a seed-inspired hydrogel with a micro-ecosystem, which imitates characteristics of seed with high intestinal adaptability, for the elimination of harmful metabolites in liver failure using a cascade reaction triggered by encapsulated microbes. Focusing on abnormal ammonia assimilation and intestinal oxygen metabolism, a two-component artificial microbiota was constructed to enable efficient intestinal oxygen consumption and subsequent hypoxia-induced ammonia elimination. More importantly, we imitated plant seeds with high adaptability to the intestinal environment to improve the performance of bacteria. A hydrogel particle with the seed shape, lignin coating, and porous structure, for achieving intentional retention, bacterial protection, and diffusion promotion, respectively was prepared. In murine and porcine models of liver failure, the artificial reactor lowered the blood ammonia to prevent nerve damage, and consumed oxygen to inhibit pathogenic facultative anaerobes for alleviating liver failure. This work underscores the great potential of medication with a bioinspired micro-ecosystem for liver failure.

Effects of dietary triiodothyronine or dopamine on small intestinal oxygen consumption in chicks.

This study aimed to investigate the effects of triiodothyronine (T3)- or dopamine (Dp)-supplemented diets on oxygen consumption by Na+, K+-ATPase activity in broiler chicks. Five groups, each with twenty-four 6-day-old chicks, randomly received one of the five dietary treatments: (1) Basal diet (commercial broiler rations with 23.0% crude protein and 3,133 kcal metabolizable energy/kg) or CON, (2) basal diet plus 0.7 μmol Dp/kg diet or Dp0.7, (3) basal diet plus 2.4 μmol Dp/kg diet or Dp2.4, (4) basal diet plus 1.9 μmol T3/kg diet or T1.9, and (5) basal diet plus 3.8 μmol T3/kg diet or T3.8 from 6 to 14 days of age. There were four replicates per treatment and 120 birds in total. At 14 days of age, three chicks from each replicate of each treatment were pooled into a flock and fed commercial broiler diets until 7 weeks of age. Compared to CON group, birds fed with T3-supplemented diets had lower thyroid, abdominal fat pad, gizzard and pancreas weight, and heavier heart weight adjusted for fasted body weight. Chicks with T1.9 had lower ileal densities at 14 day old compared with those in Dp groups or CON. Chicks with T3.8 exhibited greater duodenal and jejunal O2 consumptions as well as ouabain-sensitive O2 consumptions of jejunum and small intestine (duodenum, jejunum, and ileum) by 46.5%, 58.3%, 40.6%, and 26.4% increases, than those in CON. Partial correlation analysis revealed that the weight and length of the small intestine were negatively correlated with body weight gain. Oxygen consumption in the various small intestinal segments was negatively correlated with their respective densities (mg/mm2). In conclusion, a greater oxygen requirement for maintaining ouabain-sensitive respiration (Na+-K+-ATPase) in the intestine limits energy availability to support gastrointestinal tract growth and, thereby, may result in lower body weight gain.

Systemic and microcirculatory responses to progressive hemorrhage

To compare systemic hemodynamics with microcirculatory changes at different vascular beds during progressive hemorrhage. University-based research laboratory. Twelve anesthetized, mechanically ventilated sheep. Sheep were randomly assigned to HEMORRHAGE or CONTROL group. In the HEMORRHAGE group (n = 8), three stepwise bleedings of 5 ml/kg at 30-min intervals were performed to add up 15 ml/kg. In the CONTROL group (n = 4), sheep had the same surgical preparation but were not bled. Progressive bleeding decreased cardiac output, and superior mesenteric artery blood flow, and systemic and intestinal oxygen transports from the first step of bleeding whereas systemic and intestinal oxygen consumption remained unchanged. Mean arterial blood pressure, arterial pH and base excess, and intramucosal-arterial PCO(2) were only significantly modified in the last step of bleeding. Arterial lactate increased and sublingual, and intestinal serosal and mucosal capillary microvascular flow indexes and red blood cell velocities progressively decreased after the first step of bleeding (3.0 +/- 0.1 vs. 2.3 +/- 0.4, 3.2 +/- 0.2 vs. 2.4 +/- 0.6, 3.0 +/- 0.0 vs. 2.0 +/- 0.2, and 1,082 +/- 29 vs. 977 +/- 79, 1,042 +/- 24 vs. 953 +/- 60, 287 +/- 65 vs. 262 +/- 16 mum/s; P < 0.05 for all). Alterations in sublingual, intestinal microcirculation, and arterial lactate simultaneously arose from the first step of bleeding. The microcirculatory changes were identified either by semi-quantitative flow index or by quantitative red blood cell velocity measurements.

Direct-Fed Microbial PrimaLac and Salinomycin Modulate Whole-Body and Intestinal Oxygen Consumption and Intestinal Mucosal Cytokine Production in the Broiler Chick

The current study investigated whole-body O2 consumption, intestinal O2 consumption, and intestinal inflammation status through mucosal cytokine production on broiler chicks fed the direct-fed microbial PrimaLac. One hundred twenty 1-d-old broiler chicks were randomly assigned to 1 of 3 experimental diets: standard starter diet (control), standard starter diet with added salinomycin (SAL), and standard starter diet with added PrimaLac (DFM). Birds were housed in 2 separate rooms, the control and SAL treatments in one room and the DFM in another. Intact ileal and cecal samples were collected on d 19, 20, and 21 after measuring whole-body O2 consumption using indirect calorimetry. The O2 up-take of ileal tissue was measured using an in vitro O2 monitor. Analysis of intestinal immune status of broilers was measured by the relative differences in mRNA of both pro- and antiinflammatory cytokines: interleukin-(IL) 1β, IL-6, and IL-10 using real-time reverse transcription-PCR. Broilers exhibited a 6 to 16% decrease in whole-body energy expenditures and up to a 47% decrease (P < 0.05) in ileal energy expenditures in the DFM group compared with other treatments. The reverse transcription-PCR data demonstrated that DFM consortium numerically altered both pro- and antiinflammatory cytokines within the ileum of 19-d posthatch broilers. These data suggest that direct-fed microbials like PrimaLac increase metabolic efficiency via changes in intestinal physiology and metabolism.

Avaliação inicial dos gradientes sistêmicos e regionais da pCO2 como marcadores de hipoperfusão mesentérica

Mesenteric ischemia is a life-threatening emergency with a mortality rates still ranging between 60% and 100%. To evaluate the systemic and regional pCO2 gradients changes induced by mesenteric ischemia-reperfusion injury. In addition, we sought to determine if other systemic marker of splanchnic hypoperfusion could detect the initial changes in intestinal mucosal microcirculation after superior mesenteric artery occlusion. Seven pentobarbital anesthetized mongrel dogs (20.6 +/- 1.1 kg) were subjected to superior mesenteric artery occlusion for 45 minutes, and followed for an additional 120 minutes. Systemic hemodynamic was evaluated through a Swan-Ganz and arterial catheters, while gastrointestinal tract perfusion by superior mesenteric vein and jejunal serosal blood flows (ultrasonic flowprobe). Intestinal oxygen delivery, extraction and consumption (DO2intest, ERO2intest and VO2intest, respectively), intramucosal pH (gas tonometry), and mesenteric-arterial and mucosal arterial pCO2 gradients (D(vm-a)pCO2 and D(t-a)pCO2, respectively) were calculated. Superior mesenteric artery occlusion was not associated with significant changes on systemic hemodynamics parameters. A significant increase of D(vm-a)pCO2 (1.7 +/- 0.5 to 5.7 +/- 1.8 mm Hg) and D(t-a)pCO2 (8.2 +/- 4.8 to 48.7 +/- 4.6 mm Hg) were detected. During the reperfusion period a significant decrease on DO2intest (67.7 +/- 9.9 to 38.8 +/- 5.3 mL/min) and a compensatory increase on ERO2intest from 5.0 +/- 1.1% to 12.4 +/- 2.7% was observed. We conclude that gas tonometry can detect the mesenteric blood flow disturbances sooner than other analyzed parameters. Additionally, we demonstrated that changes on systemic or regional pCO2 gradients are not able to detect the magnitude of intestinal mucosal blood flow reduction after mesenteric ischemia-reperfusion injury.

Increased blood flow prevents intramucosal acidosis in sheep endotoxemia: a controlled study

IntroductionIncreased intramucosal–arterial carbon dioxide tension (PCO2) difference (ΔPCO2) is common in experimental endotoxemia. However, its meaning remains controversial because it has been ascribed to hypoperfusion of intestinal villi or to cytopathic hypoxia. Our hypothesis was that increased blood flow could prevent the increase in ΔPCO2.MethodsIn 19 anesthetized and mechanically ventilated sheep, we measured cardiac output, superior mesenteric blood flow, lactate, gases, hemoglobin and oxygen saturations in arterial, mixed venous and mesenteric venous blood, and ileal intramucosal PCO2 by saline tonometry. Intestinal oxygen transport and consumption were calculated. After basal measurements, sheep were assigned to the following groups, for 120 min: (1) sham (n = 6), (2) normal blood flow (n = 7) and (3) increased blood flow (n = 6). Escherichia coli lipopolysaccharide (5 μg/kg) was injected in the last two groups. Saline solution was used to maintain blood flood at basal levels in the sham and normal blood flow groups, or to increase it to about 50% of basal in the increased blood flow group.ResultsIn the normal blood flow group, systemic and intestinal oxygen transport and consumption were preserved, but ΔPCO2 increased (basal versus 120 min endotoxemia, 7 ± 4 versus 19 ± 4 mmHg; P < 0.001) and metabolic acidosis with a high anion gap ensued (arterial pH 7.39 versus 7.35; anion gap 15 ± 3 versus 18 ± 2 mmol/l; P < 0.001 for both). Increased blood flow prevented the elevation in ΔPCO2 (5 ± 7 versus 9 ± 6 mmHg; P = not significant). However, anion-gap metabolic acidosis was deeper (7.42 versus 7.25; 16 ± 3 versus 22 ± 3 mmol/l; P < 0.001 for both).ConclusionsIn this model of endotoxemia, intramucosal acidosis was corrected by increased blood flow and so might follow tissue hypoperfusion. In contrast, anion-gap metabolic acidosis was left uncorrected and even worsened with aggressive volume expansion. These results point to different mechanisms generating both alterations.

Effect of live weight gain of steers during winter grazing: II. Visceral organ mass, cellularity, and oxygen consumption.

Two experiments were conducted to examine the effect of BW gain during winter grazing on mass, cellularity, and oxygen consumption of splanchnic tissues before and after the feedlot finishing phase. In each experiment, 48 fall-weaned Angus x Angus-Hereford steer calves were assigned randomly to one of three treatments: 1) high rate of BW gain grazing winter wheat (HGW), 2) low rate of BW gain grazing winter wheat (LGW), or 3) grazing dormant tallgrass native range supplemented with 0.91 kg/d of a 41% CP supplement (NR). At the end of winter grazing, four steers were selected randomly from each treatment for initial slaughter to measure organ mass, cellularity, and oxygen consumption. All remaining steers were placed into a feedlot and fed to the same backfat end point (1.27 cm). Six steers were selected randomly from each treatment for final organ mass, cellularity, and oxygen consumption. Initial empty BW (EBW) was greatest (P < 0.001) for HGW, intermediate for LGW, and least for NR steers in both Exp. 1 and 2 (355 > 263 > 207 +/- 6.5 kg and 337 > 274 > 205 +/- 8.7 kg, respectively). For both experiments, the initial total gastrointestinal tract (GIT; g/kg of EBW) proportional weight was greater (P < 0.05) in NR steers than in LGW, and LGW steers had greater (P < 0.05) initial GIT proportional weight than HGW steers. Proportional weight of total splanchnic tissues (TST; g/kg of EBW) did not differ (P < 0.19) among treatments. Initial duodenal RNA concentration and RNA:protein were greater (P < 0.02) in LGW than in HGW steers, and NR steers were intermediate. Initial in vitro liver O2 consumption was greater (P < 0.09) in HGW and LGW than in NR steers (34.5 > 16.9 mL/min), whereas initial small intestinal oxygen consumption was greater (P < 0.01) in LGW than in HGW and NR steers (12.1 > 5.2 mL/min). Ruminal papillae oxygen consumption did not differ (P < 0.55) among treatments. The rate of decrease of GIT (g x g EBW(-1) x d(-1)) during finishing was greater in NR than in HGW and LGW steers in both Exp. 1 and 2, but mesenteric fat (g x g EBW(-1) x d(-1)) increased for NR steers, resulting in a similar (P < 0.75) increase in TST across the finishing period for all treatments. Similar rates of increase in TST across the finishing phase corresponded with similar rates of live and carcass weight gain among treatments. Our data support the hypothesis that increased visceral organ mass increases maintenance energy requirements of growing cattle.

Comparison of small intestinal enterocyte oxygen consumption in chicken lines genetically selected for divergent production traits

Comparison of small intestinal enterocyte oxygen consumption in chicken lines genetically selected for divergent production traits

Enteral feeding.

In this review, topics with scientific strength, topical interest, and controversy were selected. Over the past 50 years, malnutrition has become increasingly recognized as a cause of increased morbidity and mortality in hospital patients. From 1970 to 1980, parenteral nutrition was advocated as the most appropriate form of nutritional therapy for hospital patients. Since then, parenteral nutrition has been replaced by enteral nutrition as the best way of delivering nutrients to hospital patients. The timing of enteral nutrition has been debated. Should it be instituted early, within the first 24 hours? In addition, enteral nutrition containing immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides has been advocated for critically ill patients. The relative merits of enteral versus total parenteral nutrition continue to be debated. Questions about possible complications related to enteral nutrition have been raised. Patients are at risk of nosocomial pneumonia from aspiration and at risk of bowel ischemia because enteral nutrition increases intestinal oxygen consumption. Steroids are often used to treat Crohn disease, but because of undesirable side effects, various techniques have been used to reduce steroid dependency. Enteral nutrition has been advocated as a way of reducing steroid dependency. Finally, enteral nutrition is routinely used to feed demented patients and those in a vegetative state. It is not clear whether this practice alters outcome or quality of life.

Intestinal and cerebral oxygenation during severe isovolemic hemodilution and subsequent hyperoxic ventilation in a pig model.

During severe isovolemic hemodilution, determination of critical hematocrit levels for the microvascular oxygenation of different organs might provide more insight into the effect of the redistribution of blood flow and oxygen delivery on the oxygenation of different organs. The effect of an increased amount of dissolved oxygen on tissue oxygenation during severely decreased hematocrit levels is not clear. Fifteen anesthetized pigs were randomized between an experimental group (n = 10), in which severe isovolemic hemodilution was performed with 6% hydroxyethylstarch (1:1), and a time-matched control group (n = 5). Systemic, intestinal, and cerebral hemodynamic and oxygenation parameters were monitored. Microvascular oxygen partial pressure (muPo(2) ) was measured in the cerebral cortex and the intestinal serosa and mucosa, using the oxygen-dependent quenching of Pd-porphyrin phosphorescence. In the final phase of the experiment, fraction of inspired oxygen was increased to 1.0. Hemodilution decreased hematocrit from 25.3 +/- 3.0 to 7.6 +/- 1.2% (mean +/- SD). Systemic and intestinal oxygen delivery fell with the onset of hemodilution; intestinal oxygen consumption deceased at a hematocrit of 9.9%, whereas the systemic oxygen consumption decreased at a hematocrit of 7.6%. During hemodilution, the intestinal and cerebral oxygen extraction ratios increased from baseline with 130 and 52%, respectively. Based on the intersection of the two best-fit regression lines, determined by a least sum of squares technique, similar critical hematocrit levels were found for systemic oxygen consumption and the cerebral and intestinal mucosa muPo(2); the intestinal serosa muPo(2) decreased at an earlier stage (P < 0.05). Hyperoxic ventilation improved the muPo(2) values but not systemic or intestinal oxygen consumption. During isovolemic hemodilution, the diminished oxygen supply was redistributed in favor of organs with a lower capacity to increase oxygen extraction. It is hypothesized that redirection of the oxygen supply within the intestines resulted in the preservation of oxygen consumption and mucosal muPo(2) compared with serosal muPo(2).

Enteral feeding

In this review, topics with scientific strength, topical interest, and controversy were selected. Over the past 50 years, malnutrition has become increasingly recognized as a cause of increased morbidity and mortality in hospital patients. From 1970 to 1980, parenteral nutrition was advocated as the most appropriate form of nutritional therapy for hospital patients. Since then, parenteral nutrition has been replaced by enteral nutrition as the best way of delivering nutrients to hospital patients. The timing of enteral nutrition has been debated. Should it be instituted early, within the first 24 hours? In addition, enteral nutrition containing immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides has been advocated for critically ill patients. The relative merits of enteral versus total parenteral nutrition continue to be debated. Questions about possible complications related to enteral nutrition have been raised. Patients are at risk of nosocomial pneumonia from aspiration and at risk of bowel ischemia because enteral nutrition increases intestinal oxygen consumption. Steroids are often used to treat Crohn disease, but because of undesirable side effects, various techniques have been used to reduce steroid dependency. Enteral nutrition has been advocated as a way of reducing steroid dependency. Finally, enteral nutrition is routinely used to feed demented patients and those in a vegetative state. It is not clear whether this practice alters outcome or quality of life.

The effect of the transfusion of stored RBCs on intestinal microvascular oxygenation in the rat.

Although it is known that the transfusion of stored RBCs does not always improve tissue O(2) consumption under conditions of limited tissue oxygenation, the efficiency of O(2) delivery to the microcirculation by stored RBCs has never been determined. In a rat hemorrhagic shock model, the effects of resuscitation with fresh or 28-day-old RBCs stored in CPD plasma, saline-adenine-glucose-mannitol, and CPDA-1 plasma were investigated. Systemic hemodynamic and intestinal oxygenation measures were monitored. Intestinal microvascular PO(2) was determined with the O(2)-dependent quenching of palladium-porphyrin phosphorescence, and the RBC deformability was measured with a Laser-assisted optic rotational cell analyzer. Hemodynamic and oxygenation measures were significantly decreased during hemorrhagic shock. Intestinal oxygen consumption and mesenteric venous pO(2) were restored with the transfusion of both fresh and stored RBCs, except for CPD-stored RBCs. The intestinal microvascular pO(2) improved only with the transfusion of fresh RBCs. Deformability of the stored RBCs was significantly decreased. In contrast to that of fresh RBCs, the transfusion of stored RBCs did not restore the microcirculatory oxygenation, possibly because of impaired O(2) unloading, but, except for CPD-stored RBCs, the storage-induced changes were not enough to impair intestinal VO(2) and mesenteric venous pO(2).

Effects of hemorrhage on gastrointestinal oxygenation.

(1) To demonstrate that metabolic parameters are better indicators of tissue hypoxia than regional and whole oxygen consumption (VO(2)). (2) To compare intramucosal pH (pHi) in different gastrointestinal segments. Prospective, interventional study. Research laboratory at a university center. Fourteen anesthetized, mechanically ventilated dogs. Twenty milliliters per kilogram bleeding. We placed pulmonary, aortic and mesenteric venous catheters, and an electromagnetic flow probe in the superior mesenteric artery, and gastric, jejunal and ileal tonometers to measure flows, arterial and venous blood gases and lactate, and intramucosal PCO(2). We calculated systemic and intestinal oxygen transport (DO(2)) and consumption (VO(2)), pHi and arterial minus intramucosal PCO(2) (DeltaPCO(2)). Then, we bled the dogs and repeated the measurements after 30 min. Systemic and intestinal DO(2) fell (26.0+/-7.3 versus 8.9+/-2.6 and 71.9+/-17.3 versus 24.6+/-9.6 ml/min per kg, respectively, p<0.0001). Systemic and intestinal VO(2) remained unchanged (5.5+/-1.3 versus 5.4+/-1.3 and 15.7+/-5.0 versus 14.9+/-5.3 ml/min per kg, respectively). Gastric, jejunal and ileal pHi (7.13+/-0.11 versus 6.96+/-0.17, 7.18+/-0.06 versus 6.97+/-0.15, 7.12+/-0.11 versus 6.94+/-0.14, p<0.05) and DeltaPCO(2) (21+/-13 versus 35+/-23, 15+/-5 versus 33+/-16, 23+/-17 versus 38+/-20, p<0.05) changed accordingly. Arterial and mesenteric venous lactate and their difference, rose significantly (1.7+/-0.9 versus 3.7+/-1.4 and 1.8+/-0.8 versus 4.3+/-1.5 mmol/l, 0.1+/-0.6 versus 0.6+/-0.7 mmol/l, p<0.05). During hemorrhage, systemic and intestinal VO(2) remained stable. However, hyperlactatemia and intramucosal acidosis evidenced anaerobic metabolism. pHi changes paralleled in the three intestinal segments.

Preservation of intestinal microvascular PO2 during normovolemic hemodilution in a rat model

The effect of hemodilution on the intestinal microcirculatory oxygenation is not clear. The aim of this study was to determine the effect of moderate normovolemic hemodilution on intestinal microvascular partial oxygen pressure (Po2) and its relation to the mesenteric venous Po2 (Pmvo2). Normovolemic hemodilution was performed in 13 anesthetized male Wistar rats. Systemic hemodynamic and intestinal oxygenation parameters were monitored. Intestinal microvascular Po2 was measured by using the oxygen-dependent quenching of palladium-porphyrin phosphorescence. Hemodilution decreased systemic hematocrit from 45.0% ± 0.1% (average ± SEM) to 24.6% ± 1.6%. The mesenteric blood flow did not change from baseline values, resulting in a linear decrease in intestinal oxygen delivery (from 2.77 ± 0.15 to 1.42 ± 0.11 mL·kg–1·min–1). The intestinal oxygen extraction ratio increased significantly from 24% ± 1% to 42% ± 4%. Pmvo2 decreased significantly (from 57 ± 2 to 41 ± 2 mm Hg), but intestinal oxygen consumption and microvascular Po2 remained unaffected. As a result, the difference between microvascular Po2 and Pmvo2 increased significantly during hemodilution. Intestinal microvascular Po2 and oxygen consumption were well preserved during moderate normo-volemic hemodilution. These results might be explained by the notion of others that hemodilution induces recruitment of capillaries, resulting in redistribution of the intestinal blood flow in favor of the microcirculation, which allows a more efficient extraction of oxygen. These findings further indicate that the use of venous Po2 values as indicators of microvascular oxygenation may be misleading. (J Lab Clin Med 2000;135:476-83)

Influence of gut alkalinity and oxygen status on mobilization and size-class distribution of humic acids in the hindgut of soil-feeding termites

The majority of termite species do not feed on wood, but have a humivorous mode of nutrition. However, the exact nature of the carbon and energy source of soil-feeding termites, and also the role of the extreme alkalinity in their anterior hindguts are still unknown. Using soil-feeding Cubitermes species and high-pressure gel-permeation chromatography, we found a significant shift toward lower molecular weight in the humic acid samples extracted from different hindgut regions, compared to the parent soil ingested by the termites. The changes in size-class distribution were most pronounced in the highly alkaline (pH 12) P1 compartment, where the apparent molecular weight calculated for the peak maximum of the most abundant medium-molecular-weight fraction decreased by ≈30%. Microelectrode profiles demonstrated steep oxygen gradients into the alkaline hindgut compartments, caused by intestinal oxygen consumption in the gut periphery. In the less alkaline P3 region, oxygen consumption was at least partially attributable to biological processes, whereas in the highly alkaline P1 compartment, it seemed to be largely due to a chemical process. In vitro extraction of parent soil with NaOH solutions of increasing concentration confirmed that extraction efficiency of humic acids was not only enhanced by a high pH, but also by the simultaneous presence of oxygen. Similar results were obtained with 200 mM potassium carbonate solution, which mimics the pH and potassium concentration in the P1 region. However, in these experiments the pronounced molecular-weight shift found in the alkaline hindgut compartments was never observed, which indicates that additional factors must be present within the gut. We conclude that the extreme alkalinity in the anterior hindgut, supported by autoxidative processes, facilitates not only desorption of humic substances from the mineral matrix, but also decreases their molecular weight and increases their solubility. This renders so far unknown constituents of the humic matter accessible to microbial degradation in the subsequent, less alkaline hindgut compartments.

The effects of Astragalus membranaceus on oxygen consumption in the intestine.

To investigate the effects of Astragalus membranaceus (AM) on intestinal oxygen consumption both in vivo and in vitro. The oxygen consumption of the intestine was measured using an arteriovenous (A-V) O2 difference analyzer after treatment with AM in the intestinal lumen of ten healthy, anesthetized mongrel dogs. The effects of AM on the oxygen consumption of the intestinal mucosa in vitro were observed using constant volume manometers. The oxygen consumption of the intestine in vivo increased significantly (P < 0.05 or P < 0.01) after treatment with AM compared to the saline control. The oxygen consumption significantly increased after treatment with the 30% AM dilution and the 50% AM dilution compared to that of the 10% AM dilution (P < 0.05). There was no significant difference between the 30% AM dilution and the 50% AM dilution (P > 0.05). The effects of AM on oxygen consumption of the intestinal mucosa in vivo were similar to those in vivo. After treatment with the 5% AM dilution and the 1% AM dilution, the intestinal oxygen consumption increased compared to the control (Krebs Ringer phosphate buffer (KRPB)) (P < 0.05 and P < 0.01, respectively). There was no significant difference between treatment with the 10% AM dilution and the KRPB control (P > 0.05). AM improved the function of intestinal oxidative metabolism.

Intestinal oxygen uptake and glucose metabolism during nutrient absorption in the pig.

Intestinal transport of nutrients coincides with their partial catabolism in the gut. The aim of the present study was to measure intestinal oxygen consumption and nutrient metabolism after a meal or during a short fast. Nutrient and oxygen balances across the small intestine were measured in conscious 50 kg (live wt) pigs. Jejunal enterocytes were also isolated from 1-hr postprandial, postabsorptive, or 3-day fasted pigs, in order to evaluate their capacities to metabolize 5 mM glucose and 2 mM glutamine. Whatever the nutritional state, intestinal oxygen consumption was high, since 26 +/- 2% (n = 6) of the oxygen arterial supply was extracted by the small intestine. Furthermore, the consumption of a mixed meal induced a rapid and transient rise in oxygen consumption. In the postabsorptive state, the intestinal uptake of glucose (0.31 +/- 0.08 mmole/min, n = 6) was twice higher than that of glutamine. The role of glucose as a fuel was also evidenced after a 3-day fast. During nutrient absorption, glutamine was highly utilized, and lactate was produced. The capacity of enterocytes isolated from fed pigs to metabolize glucose was dramatically reduced, as was 6-phosphofructo 1-kinase activity. In contrast, intestinal muscle presented a high glycolytic capacity from glucose, suggesting that the main site of intestinal lactate production during nutrient absorption would be the muscular rather than the epithelial layer.

Influence of luminal nutrient composition on hemodynamics and oxygenation in developing intestine.

Age-related differences in the intestinal hemodynamic and oxygenation responses to carbohydrate, protein, and lipid were studied in 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets. A branch of the mesenteric vein draining an isolated loop of jejunoileum was used to measure intestinal blood flow, arteriovenous oxygen content difference, and venous and capillary pressure and to calculate oxygen uptake and vascular resistance. Fractionated intestinal flow was measured with radiolabeled microspheres. Measurements were made before and after luminal placement of either 5% glucose, 2.3% casec, or 5% corn oil. In 1-day-old animals, unlike all older age groups, total intestinal blood flow and vascular resistance were unchanged by any nutrient. Fractionated flow to the mucosa/submucosa levels did, however, increase in the intestine of 1-day-old piglets to a similar extent as that in older age groups. Placement of lipid or protein into the lumen led to increased oxygen uptake in all age groups, whereas carbohydrate absorption resulted in no increase in intestinal oxygen consumption in 1- and 3-day-old animals. In 1-day-olds, the increased oxygen consumption was achieved by enhanced oxygen extraction with no change in total blood flow, whereas all other groups demonstrated increases in blood flow and/or oxygen extraction. Compared with a mixed meal, oxygen consumption was not significantly greater for an individual nutrient component.

The Effects of Tumor Necrosis Factor on Intestinal Structure and Metabolism

Tumor necrosis factor (TNF), a polypeptide produced predominantly by activated macrophages, is an important mediator of sepsis. We analyzed the specific metabolic changes that occur in the gut following TNF administration. Following general anesthesia, hemodynamic and metabolic indices were measured serially in control dogs (n = 7) and animals receiving a continuous sublethal intravenous infusion of TNF (0.57.10(5) IU/kg/6 hours, n = 7). During TNF infusion mean arterial pressure gradually decreased despite fluid administration, which maintained wedge pressure and cardiac index, which were similar to control animals. While TNF significantly reduced intestinal blood flow to 12 +/- 3 mL/min/kg compared to 28 +/- 3 mL/min/kg (p less than 0.01) in controls, intestinal oxygen consumption was maintained due to an increased extraction rate. Despite hypoperfusion the intestinal exchange of metabolic substrate (glucose, lactate, pyruvate, alanine, glutamine, glutamate, and ammonia) was comparable between the control and TNF-infused animals. However, when substrate carbon balance across the intestinal tract was calculated, it appeared that there was a limitation in fuel availability in the TNF animals. This may be due to competition for fuel between the gut and other major organs. Fuel limitation may jeopardize rapid cell proliferation and mucosal repair and with regional hypoperfusion these processes may account for the mucosal ulcerations observed at the termination of the study.

Effects of temperature on ileal blood flow and oxygenation.

Arterial pressure, venous outflow pressure, blood flow, and arteriovenous oxygen difference were measured in autoperfused preparations of canine ileum while lumen temperature was altered in 1-5 degrees C increments (or decrements) between 31 and 40 degrees C. Neither blood flow nor vascular resistance was correlated to lumen temperature. However, both arteriovenous oxygen difference and oxygen uptake were linearly correlated with lumen temperature. The relation between ileal oxygen uptake and lumen temperature was consistent with a change in metabolic rate for a 10 degrees C change in temperature (Q10) for oxygen consumption of 2.7. These observations indicate that ambient temperature exerts a profound influence on intestinal oxygen consumption and that variations in temperature may explain the wide range of intestinal oxygen uptake values reported in the literature.