Small intestinal mucosal lesions in feline septic shock: a study on the pathogenesis

The pathogenesis of small intestinal mucosal damage in septic shock was explored in experiments on 15 cats given live E coli i.v. Villous (absorptive site) blood flow was studied by the carbon monoxide uptake technique using isolated small intestinal segments. In eight of the cats, segments were perfused intraluminally with oxygenated or nitrogenated saline. The main part of the small intestine was unperfused and served as control. Nine cats (60%) developed mucosal damage. They had significantly lower arterial blood pressure at the end of septicemia (56 +/- 6) than cats without mucosal damage (76 +/- 3 mmHg). Total intestinal blood flow was similar before or during septicemia. Villous blood flow before septicemia was 3.7 +/- 0.5 ml/min X 100 g intestine and 5.1 +/- 1.0 (n.s.) in the two groups, respectively, and remained unchanged. Intraluminal perfusion with oxygenated but not with nitrogenated saline prevented the development of mucosal damage. It was concluded that the small intestinal mucosal damage is due to hypoxia in spite of unchanged villous blood supply.     

Intestinal permeability and absorptive capacity in children with portal hypertension

BACKGROUND: Portal hypertension may affect intestinal function leading to malnutrition in children with liver disease. The aim was to determine whether children with portal hypertension with or without liver disease had impaired absorptive capacity and intestinal barrier function (intestinal permeability) and to ascertain whether these abnormalities related to changes in body composition. METHODS: Twenty-six children with portal hypertension were divided according to aetiology into: Group 1 intrahepatic (n = 15) and Group 2 prehepatic (n = 11). Thirty-five children acted as controls. Carbohydrate absorption and intestinal permeability were assessed using a sugar absorption/permeability test and a variety of anthropometric measurements were obtained. RESULTS: 3-O-methyl-D-glucose, D-xylose and L-rhamnose excretion were significantly reduced in both patient groups compared to controls (P < or = 0.008) and the differential urinary excretion of melibiose/rhamnose (intestinal permeability) was significantly increased in Group 1 only (P < 0.05). Anthropometric measurements showed low Z scores in both groups, but there was no significant (P > 0.05) difference between them. There was no significant correlation between urinary excretion of sugars. anthropometric measurements and energy intake. CONCLUSIONS: Increased portal pressure reduces the absorptive capacity of the small intestine, while liver disease itself leads to increased intestinal permeability.     

Age-related changes of intestinal absorption of α-aminoisobutyric acid,tyrosine and Tyr-D-Ala-Gly in rats

Intestinal absorption of α-aminoisobutyric acid (AIB), tyrosine (Tyr) and Tyr-D-Ala-Gly (TAG) was studied in vitro in rats of three different ages (4, 14 and 24 months old). When the sacs of everted ileum from the rats were incubated in Krebs-Henseleit buffer solution containing AIB (2.5 × 10⁻³M), Tyr (5 × 10⁻⁵M), or TAG (7.3 × 10⁻⁵M) at 37 °C for 20 minutes, the intestinal transmural transport and absorption of AIB and TAG were smaller in 24-month-old rats than in 4-month-old rats with data calculated by moles per weight (mg) of intestine. When data were calculated with moles per length (cm) of intestine, only transmural transport of AIB was smaller. After the sacs were incubated for 60 minutes transmural transport and absorpotion of AIB and Tyr were smaller in 24-month-old rats than in 4-month-old rats with data calculated by intestinal weight. Only transmural transport of tyrosine was smaller in 24-month-old rats when data were calculated by length of intestine. These results indicate that aging has a different effect on intestinal absorption of amino acids than it has on absorption of peptides.     

高渗盐胶体对失血性休克大鼠小肠黏膜形态的影响

目的:研究小容量高渗盐羟乙基淀粉液(HSH)复苏失血性休克大鼠时肠黏膜形态的变化和血清NO浓度变化.方法:SD大鼠麻醉后放血致平均动脉压40mmHg±5mmHg,维持30min,SD大鼠随机分成3组:(1)高渗盐羟乙基淀粉复合液+回输失血(HSH组);(2)乳酸林格液复苏+回输失血(LR组);(3)假休克组,只进行血管置管;观察休克前后血浆NO浓度的动态变化,并留取小肠组织观察病理改变.结果:HSH组大鼠复苏后血浆NO无明显下降,复苏前(30.03μmol/L±4.77μmol/L)和复苏后(27.33μmol/L±8.76μmol/L)比较,无显著差异(P>0.05),小肠的病理损伤也显著减轻.LR组血浆NO浓度明显降低,复苏前(28.37μmol/L±6.24μmol/L)和复苏后(17.48μmol/L±5.24μmol/L)比较,有显著差异(P<0.05),小肠的病理损伤无明显改善.结论:应用HSH有助于改善失血休克引起的肠道损伤;其机制可能与HSH减少内皮细胞功能损害有关.     

Absorption of bile acids in dog as determined by portal blood sampling: evidence for colonic absorption of bile acid conjugates

The intestinal phase of enterohepatic circulation, such as site and state of bile acid absorption, along the length of the intestinal tract has been speculated but not directly quantitated. In order to gain insight into the actual state of intestinal absorption of bile acid, the bile acid composition of portal blood from various segments of the intestinal tract was studied in dogs after loading endogenous bile acid by injection of caerulein. Total and unconjugated bile acids were determined with and without enzymatic hydrolysis, respectively. The amount of conjugated bile acids was calculated by subtracting unconjugated from total bile acids. Quantitation of cholic, chenodeoxycholic, deoxycholic and lithocholic acids and their conjugates was carried out by gas chromatography/mass spectrometry/selected ion monitoring with deuterated bile acids as internal standards. The major site of absorption of taurine-conjugated bile acid, a major conjugate form in the dog, was the distal small intestine. In addition, a considerable amount of cholic acid was found to be absorbed from the distal large intestine, the majority of which was still in the conjugated form. The pronounced absorption of the unconjugated secondary bile acid from the large intestine suggests the very active formation of the secondary bile acid in situ.     

Bacterial translocation in acute liver injury induced by D- galactosamine

Acute liver injury is associated with a high rate of infectious and septic complications. Most of these infections are produced by gram negative enteric bacteria. We evaluated bacterial translocation, intestinal permeability, blood flow, portal pressure, and intestinal microflora after induction of liver injury and 70% liver resection in the rat. The rate of translocation to both portal and arterial blood was 100% at 24 hours and 50% at 48 hours after liver resection compared with 83% to portal vein and 50% to aortic blood at both time points after acute liver injury. Translocation to intraabdominal organs (liver, spleen, and mesenteric lymph nodes) was 100% in both groups at both 24 and 48 hours. The rate of translocation increased after liver injury at 48 hours with progression of the liver injury but was decreased in the 70% liver resection group with improvement of liver function. "Total aerobic" and "total anaerobic" bacterial counts in small intestine and cecum were not affected. Pulmonary, distal small intestine, and cecal blood flow were decreased in both groups, whereas blood flow in the proximal small intestine was unaffected. Portal pressure and flow were increased after 70% liver resection, but they were decreased in acute liver injury. After acute liver injury, permeability of both distal small intestine and cecum increased, but after liver resection only cecal permeability increased. The results of this experiment show that bacterial translocation occurs in experimental acute liver injury and that its dynamic, pattern and fate are different from that observed after liver resection, which is a reversible surgical model of liver insufficiency. (Hepatology 1996 Jan;23(1):97-103)     

Acute increase by portal insulin in intestinal glucose absorption via hepatoenteral nerves in the rat

BACKGROUND & AIMS: Insulin exerts a strict short-term control of glucose disappearance by glucose storage as well as degradation in the liver and peripheral insulin target tissues, but an acute control of glucose appearance by glucose absorption in the intestine is as yet unknown. The aim of the present study was to evaluate, whether insulin acutely modulates intestinal glucose absorption. METHODS: In the isolated, nonrecirculating joint perfusion of the small bowel and liver of the rat via the celiac trunc and the superior mesenteric artery, glucose absorption was examined without and with infusion of insulin via the portal vein. RESULTS: Portal insulin enhanced acutely intestinal glucose absorption. This thus far unknown stimulatory effect of portal insulin was dose-dependent and detectable at physiological insulin concentrations. Atropine infused into the superior mesenteric artery completely prevented the insulin-dependent increase in intestinal glucose absorption, and carbachol caused a similar increase as portal insulin. CONCLUSIONS: Portal insulin dose-dependently generated a signal in the liver or portal vein. This signal was transmitted in a retrograde direction against the blood stream in the portal vein to the small intestine via hepatoenteral muscarinic nerves. This signal markedly increased intestinal glucose absorption. (Gastroenterology 1996 Jun;110(6):1863-9)     

The high metabolic cost of a functional gut

BACKGROUND & AIMS: Animal studies have shown that more than half of the dietary protein intake is used by the gut and that a large proportion of this utilization is devoted to (glyco-)protein synthesis. Recycling of these secretions may play a critical role in the regulation of overall dietary amino acid bioavailability. METHODS: Four piglets (age 32 days, 8-10 kg) bearing portal, arterial, and duodenal catheters and a portal flow probe were infused with a complete diet via the duodenum for 12 hours, followed by 12 hours of fasting. The portal balance of glucose and amino acids was measured throughout the 24-hour period. The animals also received duodenal and intravenous infusions of different lysine and threonine tracers. Measurements of intestinal tracer utilization and reappearance in the portal blood were used to calculate intestinal amino acid utilization and recycling. RESULTS: From 0 to 6 hours, one third of the protein intake appeared in the portal blood. As feeding continued, the portal glucose balance (60% of intake) was constant, but the net amino acid portal balance became progressively more positive. Significant net amino acid absorption continued for at least 6 hours after the cessation of feeding. Over 24 hours, 52% of the dietary protein intake appeared in the circulation and one third of this derived from recycled intestinal secretions. CONCLUSIONS: Intestinal recycling of amino acids contributes significantly to their systemic availability and may be a critical factor in amino acid nutrition.     

Making Sense of Gut Contents

A method for studying intestinal absorption with the aid of a catheter in the portal vein is described. The absorption of glucose from the human small intestine was estimated by simultaneous sampling of portal and arterial blood. A dose of 12 g glucose deposited intraduodenally was absorbed within approximately 1 hour, the major part of it within 30 minutes.     

Intramucosal pH measurement with tonometers for detecting gastrointestinal ischemia in porcine hemorrhagic shock

Intraluminal pCO/ was measured in the stomach, small intestine, and sigmoid colon of pigs using balloon catheters (Tonomitor). With the simultaneously determined arterial blood HCO3 concentration, the intramucosal pH (pHi) could be calculated using the Henderson-Hasselbalch equation. Cardiac output and portal venous flow were measured using Swan-Ganz catheters. A series of 35 normotensive pigs were studied to achieve normal values of cardiac output, gastrointestinal pHi, and blood flow in pigs. In another series of pigs (n = 12), hemorrhage was induced in two steps and followed by retransfusion. Five additional animals served as controls. Gastric, small intestinal, and colonic pHi decreased with increasing degree of hemorrhage but remained unchanged in the controls. Following severe hemorrhage, pHi fell below the normal range in all pigs but one. It recovered only partly following retransfusion. Histological examination of specimens obtained following retransfusion revealed normal mucosa in six of eight investigated animals and superficial mucosal injury in the remainder, indicating that abnormal pHi may be found for a period in the microscopically normal gastro-intestinal mucosa. Monitoring pHi in the stomach, small intestine, or colon using tonometers could be a useful technique to reveal insufficient mucosal blood flow in the alimentary canal.     

Rapid absorption of luminal polyamines in a rat small intestine ex vivo model

BACKGROUND AND AIM: Not only biosynthesis, but also uptake from the intestinal lumen, are important polyamine sources. However, there has been no information regarding dynamic polyamine transport in the small intestine. We evaluated polyamine uptake from the small intestine using a rat ex vivo model. METHODS: The organ block consisting of the small intestine and blood vessels was used. The isolated small intestine was placed in a warmed saline bath and perfused in a non-circulating manner via the superior mesenteric artery. Radio-labeled putrescine, spermidine or spermine (7.4 x 104 Bq), with 1.0 mL of phosphate buffer saline (pH 7.4) was instilled into the jejunal lumen for 1 min. Blood samples from the portal vein were collected and sample radioactivity was determined. In another experiment, an immunohistochemical study of polyamine was performed. RESULTS: After 14C-polyamine instillation, radioactivity in the portal vein samples immediately increased and then decreased gradually. The absorptive pattern did not differ among the three polyamines. The recovery rates from radioactivity at the portal vein among the three polyamines were approximately 61-76% during the initial 10 min after the administration of 14C-polyamine, and were not different from each other. Aminoguanidine, which inhibits putrescine degradation, significantly suppressed initial putrescine uptake and recovery percentage. The intraluminal administration of spermine caused an increase in the immunoreactivity of the spermine antibody in the intestinal villi. CONCLUSION: Luminal polyamines were rapidly absorbed by the intestinal mucosa and then subsequently transferred into the portal vein using a rat ex vivo model. The prior administration of aminoguanidine significantly inhibited initial putrescine transport into the portal vein.     

Hepatic arterial and portal flow in cardiogenic and hemorrhagic shock in awake dogs

The changes in liver blood flow produced by experimental cardiogenic and hemorrhagic shock are relatively unexplored. Fifteen unanesthetized dogs in which electromagnetic blood flow transducers had been implanted on the common hepatic artery and portal vein were subjected to acute myocardial infarction by mercury embolization of the circumflex coronary artery. Another group of ten dogs were bled to an arterial pressure of 40 mmHg and maintained at that level for 2 hours before reinfusion. Six additional dogs in which blood flow transducers had been implanted on the superior mesenteric artery and portal vein also were subjected to hemorrhage. In three of the six, phenoxybenzamine was infused directly into the superior mesenteric artery 45 minutes prior to bleed-out. During cardiogenic shock, both hepatic arterial and protal venous flow fell. However, whereas protal flow continued to fall, eventually stabilizing at values 36 +/- 3% of control, hepatic arterial flow subsequently rose, reaching values 93 +/- 9% above control. Total liver blood flow, after an initial decline to 53 +/- 4% of control levels rose as a result of the increased hepatic arterial flow to 73 +/- 4% of control values. During hemorrhage, both hepatic arterial and protal venous flows decreased as aortic pressure fell. Within 5 minutes of reinfusion, hepatic arterial flow surpassed its control values. Portal flow also increased but, on a percentage basis, not to so great an extent. Flow in hepatic artery remained high for 40 minutes after reinfusion, whereas portal flow rapidly decreased to levels seen at the end of hemorrhage. In hemorrhage without alpha-adrenergic receptor blockade the superior mesenteric bed constricted, thereby supporting systemic pressure. With alpha-adrenergic blockade, however, mesenteric flow became pressure-dependent and no longer acted as a homeostatic mechanism.     

Porcine intestinal ammonia liberation. Influence of food intake, lactulose and neomycin treatment

Lactulose and neomycin have, besides influencing ammonia production of the intestinal flora, been proposed to reduce glutamine-dependent ammonia formation. To test this hypothesis we determined the effects of lactulose and neomycin on the release or uptake of ammonia, urea, and amino acids across the intestine of freely moving healthy pigs. Blood was sampled from catheterized piglets (20 +/- 0.8 kg; n = 6) before and 1, 2, 3, and 6 h after a standard pig meal (750 g, 12% protein). After a week of lactulose (Legendal; 2 x 60 g/day) or neomycin (8 g/day) treatment this procedure was repeated. Electromagnetic portal and small bowel flow measurements were carried out in separate groups of pigs. Flow measurements were independent of the kind of food ingested. No significant alterations in flow could be detected during the 6 h study period. Portal and porto-arterial ammonia differences were significantly decreased after lactulose (-20%) and neomycin (-35%) treatment. alpha-Amino-nitrogen absorption decreased in both groups as compared to controls, but this decrease did not reach significance. Systemic and portal glutamine levels as well as intestinal glutamine utilization were significantly lower in the treatment groups. Citrulline and glutamate levels and intestinal production decreased after treatment. In this in vivo model, ammonia liberation after protein meals decreased in animals pretreated with lactulose or neomycin. The decreased systemic and consequently intestinal glutamine utilization may contribute to a reduction of endogenous ammonia formation in the gut wall. Diminished absorption from the gut of alpha-amino-nitrogen may, however, also contribute to a decrease in ammonia production.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional differences in microvascular response in rat intestine during acute elevation of portal pressure

The effect of acute elevation of portal pressure on the blood flow of rat intestinal microvessels was studied using a laser Doppler velocimeter and in vivo microscopy. The total intestinal blood flow decreased when portal pressure increased more than + 15 cmH₂O above the basal value. Blood flow in villus capillaries did not change at portal pressures of + 5 to + 15 cmH₂O, but did decrease at + 20 cmH₂O. Blood flow in muscle capillaries decreased at all steps of portal hypertension. Red blood cell velocity was decreased by portal hypertension in large venules, but not in small venules of the submucosa. Large venules, but not small venules, dilated in acute portal hypertension. Large arterioles in the submucosa constricted, while small arterioles dilated at portal pressures of + 10 to + 15 cmH₂O. In conclusion, the intestinal microvascular flow response differs according to the degree of portal hypertension and the location on the microvascular tree. Blood flow in villus capillaries and in small submucosal venules is maintained at a small degree of portal hypertension.     

Selective and non-selective beta receptor blockade in the reduction of portal pressure in patients with cirrhosis and portal hypertension.

To elucidate the mechanisms by which beta receptor blockade leads to a reduction of portal pressure, 18 patients with cirrhosis and portal hypertension were given comparable doses of propranolol or metoprolol. The fall in portal pressure was more marked with propranolol together with a significant reduction in hepatic blood flow, which was not seen with metoprolol. No correlation between the reduction in cardiac output and the decrease in portal pressure or changes in hepatic blood flow could be elicited in each group, but there was a direct relationship between the decrease in hepatic blood flow and fall in portal pressure in the propranolol treated patients. The difference observed may be related to blockade of beta 2 vasodilator receptors in the splanchnic circulation which will occur only with propranolol and lead to a greater fall in splanchnic blood flow than will be produced by a reduction in cardiac output alone. Metoprolol, by maintaining effective hepatic blood flow, may be preferable to propranolol in patients with severely impaired liver function.     

The digestive adaptation of flying vertebrates: high intestinal paracellular absorption compensates for smaller guts

Anecdotal evidence suggests that birds have smaller intestines than mammals. In the present analysis, we show that small birds and bats have significantly shorter small intestines and less small intestine nominal (smooth bore tube) surface area than similarly sized nonflying mammals. The corresponding >50% reduction in intestinal volume and hence mass of digesta carried is advantageous because the energetic costs of flight increase with load carried. But, a central dilemma is how birds and bats satisfy relatively high energy needs with less absorptive surface area. Here, we further show that an enhanced paracellular pathway for intestinal absorption of water-soluble nutrients such as glucose and amino acids may compensate for reduced small intestines in volant vertebrates. The evidence is that l-rhamnose and other similarly sized, metabolically inert, nonactively transported monosaccharides are absorbed significantly more in small birds and bats than in nonflying mammals. To broaden our comparison and test the veracity of our finding we surveyed the literature for other similar studies of paracellular absorption. The patterns found in our focal species held up when we included other species surveyed in our analysis. Significantly greater amplification of digestive surface area by villi in small birds, also uncovered by our analysis, may provide one mechanistic explanation for the observation of higher paracellular absorption relative to nonflying mammals. It appears that reduced intestinal size and relatively enhanced intestinal paracellular absorption can be added to the suite of adaptations that have evolved in actively flying vertebrates.     

Relationship between intestinal volume secretion and oxygen uptake

The effects of net volume secretion on blood flow, oxygen extraction, and oxygen uptake were analyzed in autoperfused segments of cat ileum. Intestinal secretion was induced by local intraarterial infusion of glucagon, histamine, theophylline, prostaglandin E₁ or vasoactive intestinal peptide, and, by intraluminal placement of cholera toxin or ricinoleic acid. Net volume secretion rates were determined using a volume recovery method. Intestinal oxygen uptake was increased by all secretagogues. The increased oxygen uptake by the secreting intestine resulted from an increased blood flow or oxygen extraction or both. Significant positive correlations between intestinal oxygen uptake and secretion rate were acquired only during cholera toxin, theophylline, and prostaglandin E₁, secretion. The results indicate that the metabolic work incurred in the small bowel during secretory states greatly exceeds that reported for the absorptive state.     

Intestinal microvascular adaptation to chronic portal hypertension in the rat

Microvascular pressures, diameters, and flow velocities were measured in the small intestine of rats with chronic stenosis of the portal vein. Ten days after portal vein stenosis, portal venous pressure increased (13.8 +/- 0.4 mmHg vs, 7.3 +/- 0.5 mmHg; p less than 0.05) whereas systemic arterial pressure decreased (94.2 +/- 2.0 mmHg vs. 106.5 +/- 1.6 mmHg; p less than 0.05). Red blood cell centerline velocity, measured in first-order arterioles, was significantly higher in portal hypertensive rats (24.3 +/- 1.2 mm/s vs. 19.6 +/- 1.3 mm/s), yet there was no significant change in the diameters of these vessels. Microvascular pressures and diameters of first- and second-order arterioles were not different between control and portal hypertensive rats. However, both pressure (34.3 +/- 2.7 mmHg vs. 28.0 +/- 1.8 mmHg) and diameter (30.4 +/- 0.6 microns vs. 21.4 +/- 2.1 microns) were significantly increased in the third-order arterioles of portal hypertensive rats. A consistent elevation in pressure was observed throughout the distal segments (capillaries to first-order venules) of the intestinal microcirculation of portal hypertensive rats. The results of these studies indicate that the increased intestinal vascular pressures associated with chronic portal hypertension result from a combination of reduced arteriolar resistance and venous congestion.     

Effect of portal hypertension onIn Vivo bile acid-mediated small intestinal mucosal injury in the rat

This study's purpose was to determine whether portal hypertension adversely affects small intestinal mucosal injury. Portal hypertension was produced in male Sprague-Dawley rats by two-stage ligation of the portal vein. Sham-operated rats were used as controls. Two weeks later, intestinal injury was produced byin vivo perfusion with 5 mM chenodeoxycholic acid for 30 min. Intestinal injury was assessed by quantitative morphometry and by measuring intestinal water and mannitol absorption. Portal hypertension resulted in more injury in the distal perfused intestine as manifested by increased villus tip denudation [portal hypertensive 52.5±9.6sem) vs controls 28.1±5.7m, P=0.05). Additionally there was a significant decrease in the unperfused duodenal villus height in portal hypertensive rats (portal hypertensive 755±22 vs controls 848±28m, P<0.02). Portal hypertension had no significant effect on the increase in mannitol absorption or water secretion caused by chenodeoxycholic acid perfusion. This study suggests that portal hypertension alters small intestinal mucosa and increases susceptibility to injury.This work was supported in part by a grant from the Research Service of the Veterans Administration.     

Effects on myocardial contractility of blood-borne material released from the feline small intestine in simulated shock.

There is a pronounced derangement in cardiovascular function in the cat after a 2- or 3-hour period during which shock is simulated in the small intestine by regional hypotension (BP = 30-35 mm Hg) during activation of vasoconstrictor nerve fibers. It has been proposed that these effects are caused by blood-borne cardiode-pressant substance(s) released from the "shocked" small intestine. To obtain further evidence for this hypothesis we performed a study on two heart preparations in vitro. Rabbit papillary muscles or isolated beating rat hearts were exposed to intestinal venous plasma obtained from control cats and from cats subjected to simulated intestinal shock for 2 or 3 hours. while control plasma induced only a slight depression of myocardial contractility, plasma from "shocked" intestine caused a significant decrease in peak isometric tension of the papillary muscles or a fall in systolic pressure of the rat hearts. Since the experiments on papillary muscle indicated that time to peak tension was largely unaffected by the plasma samples, we conclude that the feline intestine in shock releases material into blood that exerts a negative inotropic effect on the myocardium.