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K D Crissinger

Publications and source records attributed to K D Crissinger.

At least 19 recordsLinked to original sources
PubMed1997

Unique crystalline inclusions in neonatal pig small intestine epithelial cells.

In this study we describe the presence of novel crystalline inclusions in the jejunal and ileal epithelium of newborn pigs. Hampshire/Yorkshire piglets (0-3 days) were anesthetized with pentobarbital and tissues were recovered following laparotomy. Sections of jejunum and ileum were prepared with a variety of fixatives for paraffin and methacrylate embedment for the light and electron microscopy. The characteristics of these crystalline structures have been demonstrated by cytochemical staining, immunohistochemical staining, and ultrastructural studies. Using light microscopy, it was determined that 10.8% of villus epithelial cells in the jejunum contained inclusions, whereas inclusions were present in 26.6% of the villus epithelial cells in the ileum. Inclusions were absent in crypt epithelial cells of both areas of the intestine, and the percentage of cells with inclusions increased towards the villus tip. Preliminary histochemical analysis has been unrevealing. The inclusions are periodic acid/Schiff's (PAS) reagent-negative, and do not stain for the presence of concentrated proteins. Using electron microscopy, the inclusions are found to be clustered in the supra-nuclear region of the cells and are generally oriented with the long axis of the cell. The crystals vary in size and have a dense core region surrounded by a regular less dense periphery.

Animals↗
PubMed1996

Intestinal oxygenation and mucosal permeability with luminal mother's milk in developing piglets.

We have previously observed a developmental difference in mucosal permeability (i.e. the younger the animal, the greater the increase in permeability) after exposure to luminal nutrients derived from cow's milk-based infant formulas. There has been tremendous speculation and some clinical evidence that mother's milk may be protective against mucosal injury in developing intestine. In this study, we hypothesized that instillation of sow's milk into the intestinal lumen of developing piglets would cause no differences in either intestinal metabolic demand (oxygen uptake) or mucosal permeability among age groups. Intestinal blood flow (total and fractionated), arteriovenous oxygen content difference, venous pressure, and capillary pressure were measured, and vascular resistance and oxygen uptake were calculated, after 30 min of intraluminal instillation of predigested and solubilized sow's milk in 1-d-old, 3-d-old, 2-wk-old, and 1-mo-old piglet jejunoileum. In a separate group of animals, plasma-to-lumen clearance of chromium-51 EDTA was evaluated during luminal perfusion with digested and solubilized sow's milk in 1-d-old, 3-d-old, and 1-mo-old piglet jejunoileum. Intestinal oxygen uptake was similar among age groups of developing piglets, but EDTA clearance was significantly higher for intestinal segments perfused with sow's milk in 1-d-old, compared with older, animals. Thus, luminal perfusion with predigested and bile acid-solubilized sow's milk in 1-d-old piglet jejunoileum, compared with perfusion in older piglets, causes increased mucosal permeability in 1-d-old intestine, but this increased permeability is not due to increased intestinal oxygen uptake (i.e. increased metabolic demand).

Animals↗
PubMed1994

An animal model of necrotizing enterocolitis induced by infant formula and ischemia in developing piglets.

BACKGROUND/AIMS: The lipid component of piglet formula (0.5% fat) causes increased mucosal permeability in 1-day-old piglets after ischemia/reperfusion. The present study examined if luminal exposure to infant formulas (3.5% fat) and ischemia/reperfusion result in an animal model of necrotizing enterocolitis and if injury is dependent on the formula fat composition. METHODS: Plasma-to-lumen clearance of 51Cr-ethylenediamine-tetraacetic acid was measured, and morphology was evaluated during luminal perfusion with preterm, term, and delipidated preterm cow milk-based infant formulas before and after ischemia/reperfusion in 1-day-old and 1-month-old piglet jejunoileum. In a separate set of experiments, a 1-2-cm segment of ileum was exteriorized and opened to expose the mucosal surface, and the villi were superfused with the above formulas (no ischemia). RESULTS: Before ischemia, clearances were markedly higher for intestinal loops perfused with preterm formula than for loops perfused with term and delipidated formulas in 1-day-old animals. After ischemia, clearances in loops perfused with preterm formula were significantly greater and grossly hemorrhagic and histologically necrotic compared with loops perfused with delipidated formula (minimal injury). Superfusion with preterm formula caused diffuse hyperemia and hemorrhage into intestinal villi. CONCLUSIONS: Luminal perfusion of 1-day-old piglet jejunoileum with predigested and bile acid-solubilized preterm infant formula, in combination with ischemia/reperfusion, produces an animal model of necrotizing enterocolitis, but only if the lipid fraction of the formula is present.

Animal Feed↗
PubMed1994

Regulation of hemodynamics and oxygenation in developing intestine: insight into the pathogenesis of necrotizing enterocolitis.

The pathogenesis of necrotizing enterocolitis remains unknown, but various factors have been postulated including, but not limited to, mesenteric ischemia, enteral alimentation, and infection. Since an understanding of circulatory physiology in developing intestine may provide insight into the role of mesenteric ischemia in the etiology of necrotizing enterocolitis, this review summarizes what is currently known about the regulation of blood flow and oxygenation in developing intestine and how it differs from that in adult intestine. The discussion is divided into intrinsic versus extrinsic factors. Phenomena which may be used to evaluate the capacity for intrinsic vasoregulation include pressure-flow autoregulation, reactive hyperemia, venous hypertension, arterial hypoxemia, and postprandial hyperemia. Extrinsic factors include neurologic and hormonal influences. Additionally, the susceptibility for tissue hypoxia as a function of age and the correlation with subsequent development of mucosal injury are discussed.

Cell Hypoxia↗
PubMed1994

Developing intestine is injured during absorption of oleic acid but not its ethyl ester.

Although lipids are essential nutrients in the mammalian diet, we have shown that fatty acids are injurious to epithelial cells of developing piglet intestine during luminal perfusion. Furthermore, the intestine of young animals sustains greater injury than that of older piglets. In an effort to understand the mechanism for this developmental injury, we investigated whether changes in the chemical configuration of oleic acid would alter this damage. Mucosal permeability, as quantitated by the plasma-to-lumen clearance of 51chromium EDTA, was evaluated during luminal perfusion with oleic acid as compared with its ethyl (ethyl oleate) and glyceryl (glycerol-1-mono-oleate) esters, solubilized with taurocholic acid, in jejunum of 1-d-, 3-d-, 2-wk-, and 1-mo-old piglets. 51Chromium EDTA clearance increased significantly during oleic acid and glycerol-1-mono-oleate perfusion, but did not increase during perfusion with ethyl oleate or saline. This result was not secondary to failure of absorption of ethyl oleate, as [14C]oleic acid and ethyl [1-14C]oleate were absorbed to a similar extent. Furthermore, developing intestine was able to remove the ethyl group and then re-esterify the fatty acid to form triacyglycerol. These studies indicate that oleic acid-induced mucosal injury can be abolished when the carboxylic group of the fatty acid is esterified with an ethyl, but not a glycerol, group. Since the ethyl ester is also absorbed and metabolized similarly to the free fatty acid, this may provide a means of supplying long-chain fatty acids to developing intestine without causing mucosal damage.

Animals↗
PubMed1993

Oleic acid-induced mucosal injury in developing piglet intestine.

A role for luminal nutrients, in particular products of lipid digestion, in the pathogenesis of mucosal injury to developing intestine has been postulated. We evaluated changes in mucosal permeability and light and electron microscopic histology induced by luminal perfusion with the long-chain fatty acid oleate in developing piglet intestine as a function of age and concentration of the fatty acid. 51Cr-labeled EDTA plasma-to-lumen clearance was measured in jejunum and ileum of 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets during sequential perfusion with saline control (20 min); 0, 1, 5, and 10 mM oleic acid/10 mM taurocholate in saline (20 min); and normal saline (60 min). The jejunum of piglets < or = 2 wk showed significantly greater increases in mucosal permeability compared with 1-mo-old animals after perfusion with oleic acid. This effect was dependent on the luminal concentration of the fatty acid and was associated with mucosal injury evident under light and electron microscopy. In contrast, the overall response in ileum was more attenuated compared with jejunum. Thus oleic acid, a common dietary fatty acid, induces dose- and age-dependent injury in developing piglet intestine. Investigation of the mechanisms of this injury may provide the basis for dietary modifications directed at decreasing the risk of mucosal injury during enteral feeding in neonatal intestine.

Aging↗
PubMed1993

Fatty acid-induced injury in developing piglet intestine: effect of degree of saturation and carbon chain length.

Luminal perfusion with the long-chain fatty acid (LCFA) oleate in concentrations similar to that found in premature infant formula produces a dose- and age-dependent mucosal injury in developing intestine. To investigate whether this lipid-induced phenomenon is a function of the degree of saturation and/or chain length of the fatty acid, 51Cr-EDTA plasma-to-lumen clearance was measured in jejunum and ileum of 1-d-, 3-d-, 2-wk-, and 1-mo-old piglets after perfusion with 5-mM solutions of different medium-chain saturated fatty acids and saturated and unsaturated LCFA. Mono- and polyunsaturated LCFA produced significant increases in jejunal permeability. In general, this effect was greater in piglets < or = 2 wk old compared with 1-mo-old animals, but no differences were observed among the unsaturated LCFA within an age group. In contrast, the alterations in mucosal permeability induced by medium-chain fatty acids were overall more attenuated than those induced by LCFA. Our results suggest that developing intestine is vulnerable to the injurious effect of dietary fatty acids and that the lipid-induced changes in mucosal permeability appear to be a function of the fatty acid chain length. The degree of saturation of the fatty acid does not alter its cytotoxic effects.

Animals↗
PubMed1992

The role of lipids in ischemia/reperfusion-induced changes in mucosal permeability in developing piglets.

This study determined which nutrient component of formula may be responsible for changes in ischemia/reperfusion-induced mucosal permeability, as quantitated by the plasma-to-lumen clearance of 51Cr-ethylenediaminetetraacetic acid, in newborn piglets. Loops of jejunoileum in 1-day-old and 1-month-old piglets were perfused with predigested and bile acid-solubilized solutions of formula, lipid, protein, carbohydrate, delipidated formula, or fatty acid during 1 hour each of control, ischemia, and reperfusion. Luminal perfusion with formula or lipid led to significantly greater increases in mucosal permeability during reperfusion in newborn intestine than did carbohydrate or protein, whereas mucosal permeability in older animals was not different among solutions. Removal of all lipids from the formula abolished the increased mucosal permeability associated with reperfusion in newborn animals. Perfusion with oleate, a monounsaturated dietary fatty acid, led to still greater increases in reperfusion-associated permeability in newborn but not older intestine. The oleate and lipid perfusions also caused significantly increased mucosal permeability in the absence of ischemia. Thus, it appears that a lipid component of formula, probably a fatty acid, is responsible for the increase in mucosal permeability induced by ischemia/reperfusion in newborn intestine and also leads to increased mucosal permeability in the absence of ischemia/reperfusion. Investigation of the mechanism of these lipid-associated changes in mucosal permeability may provide a rationale for dietary modifications that may decrease the risk of mucosal injury during feeding and ischemic stress in immature intestine.

Animals↗
PubMed1992

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.

Aging↗
PubMed1991

Postprandial hemodynamics and oxygenation in developing piglet intestine.

Age-related differences in the intestinal hemodynamic and oxygenation responses to feeding were studied in 1-day- (never-nursed and nursed-fasted), 3-day-, 2-wk-, and 1-mo-old piglets. A distal branch of the superior mesenteric vein draining an isolated loop of jejunoileum was used to measure intestinal blood flow, arteriovenous oxygen content difference, venous pressure, and capillary pressure. Calculations of oxygen uptake and vascular resistance were performed from the measured variables. Radioactive microspheres were used to measure fractionated flow. After luminal instillation of a cow milk-based formula, postprandial oxygen uptake increased to a similar extent in all age groups. In never-nursed newborns the increase was achieved by a dramatic rise in oxygen extraction with no change in total flow, while all other groups demonstrated a combined increase in blood flow and oxygen extraction. Mucosal blood flow increased to a similar extent in all age groups, but in never-nursed newborns it was at the expense of muscularis-serosa flow. Thus, because oxygen extraction and mucosal blood flow appear to be near maximal during feeding alone, newborn intestine may be at risk for tissue hypoxia and subsequent mucosal injury in the presence of a superimposed cardiovascular stress.

Aging↗
PubMed1990

Pathophysiology of gastrointestinal mucosal permeability.

The intestinal mucosa is composed of multiple barriers to the lumen-to-blood transport of solutes, including the unstirred water and mucous layers, the apical and basolateral cell membranes of the epithelial cell, the paracellular junctions, the interstitial matrix, and the capillary and lymphatic endothelia. The epithelial barrier appears effectively to restrict the movement of solutes with a radius as low as 3 A, yet it also permits limited permeation by molecules as large as albumin (36 A radius). There is evidence to suggest that the restrictive properties of the gastrointestinal mucosa are significantly altered under various physiological and pathological conditions, and measurement of plasma (or luminal) clearances of water-soluble molecules has proved to be a popular method for studying intestinal permeability. The aim of this review is to discuss the concept of the plasma clearance method, methodological aspects of the technique, factors that influence plasma-to-lumen clearance measurements (e.g. solute size, blood flow, and permeability of the epithelial cell barrier), and advantages and disadvantages of the clearance method. Finally, application of the clearance technique to the study of ischaemia/reperfusion-, ethanol-, and FMLP-induced mucosal injury will be described.

Animals↗
PubMed1990

Oxidant-induced increases in mucosal permeability in developing piglets.

Reactive oxygen metabolites have been implicated in the pathogenesis of mucosal injury induced by ischemia-reperfusion in adult animals, with recent interest centering on the capacity of polymorphonuclear neutrophil-derived oxidants to mediate this injury. A role for oxidants has also been postulated in the etiology of neonatal necrotizing enterocolitis. Based on evidence that the intrinsic capacity of the neonatal piglet intestine to detoxify hydrogen peroxide (H2O2) is minimal relative to that of older piglets, we characterized the changes in mucosal permeability induced by luminal perfusion with H2O2 and hypochlorous acid at concentrations that can be produced physiologically by activated neutrophils (0.05 mmol/L, 0.1 mmol/L, and 0.5 mmol/L), in the distal ileum of 1-d- and 1-mo-old piglets. Mucosal permeability was quantitated by measurement of blood-to-lumen clearance of 51-labeled chromium EDTA. Luminal perfusion with either H2O2 (0.05 mmol/L and 0.1 mmol/L) or hypochlorous acid (0.1 mmol/L and 0.5 mmol/L) significantly increased mucosal permeability in newborn piglets but did not affect mucosal permeability in 1-mo-old animals. Perfusion with 0.5 mmol/L H2O2 significantly increased mucosal permeability over control values in both age groups, but injury in the newborn intestine was significantly greater than that observed in 1-mo-old animals. Thus, as predicted by the reduced intrinsic capacity of the mucosa of neonatal piglets to detoxify H2O2, the ileum of newborn piglets is more vulnerable to oxidant-induced mucosal injury than is the ileum of older animals.

Age Factors↗
PubMed1989

Mucosal injury induced by ischemia and reperfusion in the piglet intestine: influences of age and feeding.

The pathogenesis of neonatal necrotizing enterocolitis is unknown, but enteral alimentation, infectious agents, and mesenteric ischemia have been frequently invoked as primary initiators of the disease. To define the vulnerability of the intestinal mucosa to ischemia and reperfusion in the developing piglet, we evaluated changes in mucosal permeability using plasma-to-lumen clearance of chromium 51-labeled ethylenediaminetetraacetic acid in the ileum of anesthetized 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets as a function of (a) duration of intestinal ischemia (20, 40, or 60 min of total superior mesenteric artery occlusion), (b) feeding status (fasted or nursed), and (c) composition of luminal perfusate (balanced salt solution vs. predigested cow milk-based formula). Baseline chromium 51-labeled ethylenediaminetetraacetic acid clearance was not significantly altered by ischemia, irrespective of duration, or feeding in all age groups. However, clearances were significantly elevated during reperfusion after 1 h of total intestinal ischemia in all age groups, whether fasted or fed. Reperfusion-induced increases in clearance did not differ among age groups when the bowel lumen was perfused with a balanced salt solution. However, luminal perfusion with formula resulted in higher clearances in 1-day-old piglets compared with all older animals. Thus, the neonatal intestine appears to be more vulnerable to mucosal injury induced by ischemia and reperfusion in the presence of formula than the intestine of older animals.

Aging↗
PubMed1989

Developmental biology of oxidant-producing enzymes and antioxidants in the piglet intestine.

The pathogenesis of neonatal necrotizing enterocolitis is unknown, but a possible role for reactive oxygen metabolites has been postulated. We evaluated whether developmental differences exist in the levels of 1) the free radical-generating enzyme xanthine oxidase, 2) granulocyte peroxidase, an index of the resident granulocyte population, 3) free radical-scavenging enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and 4) reduced glutathione, an endogenous antioxidant, in the ileal and colonic mucosa of 1-d-old, 3-d-old, 2-wk-old, and 1-mo-old piglets. We found no xanthine dehydrogenase/oxidase activity in 1-d to 1-mo-old piglets. Mucosal granulocyte peroxidase activity was higher in older animals, indicating that there was an age-dependent infiltration of granulocytes (eosinophils, neutrophils) in the distal bowel. The peroxidase activity per circulating granulocyte, however, did not vary with age. Superoxide dismutase activity was significantly higher in 1-d-old piglets than in all older age groups; glutathione peroxidase activity was significantly lower in 1-d-old animals than that of older age groups. There was no detectable catalase activity in the mucosa when tissue was corrected for catalase activity of blood. Finally, ileal GSH levels were significantly lower in 1-d-old than in 2-wk-old and 1-mo-old animals, whereas colonic reduced glutathione activity did not differ among age groups. In conclusion, the distal bowel of the neonatal piglet appears to have a limited capacity to generate oxidants via xanthine oxidase and resident granulocytes. However, the neonatal piglet intestine has a lower capacity to detoxify hydrogen peroxide than that of older animals.

Animals↗
PubMed1989

Intestinal blood flow and oxygen consumption: responses to hemorrhage in the developing piglet.

Age-related differences in the intestinal hemodynamic and oxygenation responses to arterial hemorrhage were studied in anesthetized and ventilated 1-d, 3-d, 1-wk, and 2-wk-old piglets. Steady-state values of superior mesenteric blood flow, venous pressure, and arteriovenous oxygen difference were obtained before and after 5 and 10 mL/kg arterial hemorrhage. With 5 mL/kg hemorrhage, intestinal blood flow fell significantly below baseline values, but oxygen extraction increased to maintain oxygen uptake at control levels in all age groups. In contrast to 2-wk-old piglets, the intestine of 1-d, 3-d, and 1-wk-old animals could not compensate for the greater reduction in blood flow produced by 10 mL/kg hemorrhage, resulting in a significant reduction in oxygen uptake. Thus, the intestine of developing piglets up to 1 wk of age appears to be at greater risk for tissue hypoxia induced by arterial hemorrhage than that of older animals.

Animals↗
PubMed1988

Autoregulatory escape from norepinephrine infusion: roles of adenosine and histamine.

Stimulation of sympathetic fibers or infusion of norepinephrine (NE) into the superior mesenteric artery (SMA) leads to an initial decrease in intestinal blood flow, which is followed by a return of flow toward the base-line value (autoregulatory escape) despite continued nerve stimulation or NE infusion. Although the mechanisms responsible for "autoregulatory escape" have not been defined, accumulation of vasodilator metabolites is frequently invoked to explain this phenomenon. Inasmuch as histamine and adenosine exist in high concentrations in the intestinal mucosa and both are potent vasodilators, we examined the effects of chlorpheniramine (an H1 blocker) and adenosine deaminase (degrades adenosine) on autoregulatory escape from NE infusion. In autoperfused piglet intestinal preparations, we measured SMA blood flow and the arteriovenous oxygen difference during intra-arterial NE infusion before and after blockade with chlorpheniramine or adenosine deaminase. Adenosine deaminase pretreatment increased the peak vasoconstrictor and reduced the steady-state escape responses to NE infusion. Chlorpheniramine did not affect either the vasoconstrictor or escape responses. The oxygen uptake changes induced by NE infusion were not dramatically modified by either treatment. These results indicate that adenosine but not histamine is responsible for at least part of the escape of intestinal blood flow from NE infusion.

Adenosine↗
PubMed1988

Developmental intestinal vascular responses to venous pressure elevation.

The response to venous pressure elevation is an important criterion for determining whether metabolic or myogenic mechanisms are involved in local vasoregulation. We studied the effects of venous pressure elevation on intestinal hemodynamics and oxygenation in 20 mixed-breed piglets, divided equally among 1-day-, 3-day-, 2-wk-, and 1-mo-old animals. A venous circuit was established between the superior mesenteric and jugular veins, which allowed measurement of superior mesenteric blood flow, venous pressure, capillary pressure, and arteriovenous oxygen difference at venous pressures between 0 and 20 mmHg. The resting intestinal oxygen uptake in 1-day-old piglets was significantly higher than in 2-wk-old and 1-mo-old piglets. The vascular response to venous pressure elevation in 1-day-old piglets was characterized by reductions in total and precapillary resistance and increased oxygen uptake, while older animals responded to venous pressure elevation with increases in total and precapillary vascular resistance and reductions in oxygen uptake. These results indicate that metabolic factors exert a dominant influence on the intestinal vasculature of the newborn, while myogenic factors predominate in older animals in response to venous pressure elevation.

Animals↗