Migrating motility complexes persist after severe traumatic shock in patients who tolerate enteral nutrition.

BACKGROUND: Postinjury small bowel ileus is poorly characterized and may be an important factor in intolerance to enteral nutrition (EN). We, therefore, placed jejunal manometry catheters in high-risk trauma patients. Our hypothesis was that the presence of "fasting migrating motility complex (MMC)" activity and conversion to a "fed pattern" at goal rate of EN would be present in those patients who tolerate jejunal feeding. METHODS: After obtaining baseline fasting manometry pressure tracings, jejunal feeding was advanced stepwise to a set goal while tolerance was monitored and intolerance was treated by a standard approach. RESULTS: Of the 10 study patients, 7 were able to be maintained on EN. Five (50%) had "fasting MMCs" and had good tolerance to early advancement of EN. The remaining five patients did not exhibit "fasting MMCs" and four had poor tolerance to early advancement of EN. Overall, nine patients reached goal rate of EN of which four converted to a "fed pattern." This, however, was not associated with later tolerance to EN. CONCLUSION: EN is feasible following severe traumatic shock. Surprisingly, half of the patients had fasting MMCs. This requires intact neural and motor function and was associated with good tolerance of early EN.

Differing mechanisms of stimulation of Na+ absorption in rabbit proximal colon.

Both alpha2-adrenergic agonists and decreased Na+ in the bathing fluids stimulate electroneutral Na+ absorption in rabbit proximal colon, but it is unclear whether they have similar modes of action. We sought to define regulatory events involved with stimulation of Na+ absorption by these two agonists. Transport parameters were assessed by ion flux studies under short-circuit and pH stat conditions, recordings of intracellular electrical potential difference (psi(mc)) with microelectrode impalements, and measurement of intracellular pH (pH(i)). Epinephrine elicited a yohimbine-inhibitable alkalinization of pH(i) but did not alter psi(mc) In contrast, lowered serosal Na+ concentration ([Na+]) did not significantly increase pH(i) but did depolarize psi(mc). Removal of serosal HCO(3)- stimulated Na+ absorption and reversed residual ion flux from secretion to absorption. pH stat studies demonstrated epinephrine-stimulated, amiloride-inhibitable serosal alkalinization. Serosal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibited Na+ absorption. Epinephrine and lowered [Na+] have different effects on intracellular parameters associated with electroneutral Na+ absorption. Epinephrine stimulates an apical Na+/H+ exchanger. Lowered [Na+] elicits responses consistent with a coupled Na+-HCO(3x)- exit step. Coordinated function of apical Na+/H+ exchangers and a basolateral Na+-HCO(3)(x)- symport permit Cl(-)-independent electroneutral Na+ absorption while maintaining pH(i) homeostasis. Given the low [Cl-] environment of the colonic lumen, this transport pathway may be important for electroneutral Na+ absorption.

Propionate-initiated changes in intracellular pH in rabbit colonocytes.

BACKGROUND/AIMS: Because regulation of intracellular pH (pHi) is critical to basic cell functions, most cells have evolved mechanisms to closely regulate intracellular acid-base balance. Short-chain fatty acids (SCFAs), the predominant luminal anion in the colon, acidify the cell interior in several cell systems, but their effect on their "natural target," the colonocytes, has not been examined thoroughly. METHODS: We monitored the pHi response to a model SCFA, propionate, in isolated cells and epithelial sheets from rabbit proximal colon loaded with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and -6)carboxyfluorescein. RESULTS: SCFAs induced a characteristic pHi response curve in colonocytes: an immediate acidification and a recovery phase returning to baseline in 100-200 seconds. Acidification was altered by increasing concentrations of SCFAs, by increasing SCFA chain length, extracellular osmolarity, and intracellular pH, and finally, Na+ removal. The recovery phase was slowed by amiloride and 4-alpha-OH cinnamate, an inhibitor of proton-monocarboxylate cotransport. CONCLUSIONS: Physiological concentrations of SCFAs have profound effects on intracellular pH. Simple diffusion of the SCFA may not explain the complexities of propionate-induced protonated acidification; the pH recovery phase may involve multiple processes including Na(+)-H+ exchange and H(+)-SCFA cotransport. Luminal constituents such as SCFAs may have significant effects on the intracellular pH and function of colonocytes.

Segmental differences in short-chain fatty acid transport in rabbit colon: effect of pH and Na.

Short-chain fatty acids (SCFAs) are the predominant luminal anion in the mammalian colon. Although they are rapidly absorbed in vivo, little is known about the mechanisms of transepithelial transport in vitro. Previous studies have suggested that SCFA transport may be linked to Na absorption or an anion exchange mechanism. We compared the transport of propionate under short-circuit conditions in rabbit proximal and distal colon to determine whether there were segmental differences, how SCFAs may be linked to either Na absorption or anion transport, and whether SCFAs, as weak electrolytes, may be affected by transepithelial pH gradients. In distal colon, propionate transport was not significantly altered by stimulation of electrogenic Na absorption, epinephrine or Cl removal. However, a modest transepithelial pH gradient (luminal 6.8/serosal 7.4) stimulated propionate absorption. In proximal colon, propionate transport was significantly altered by maneuvers that either stimulated (lowered [Na] in the bathing media) or inhibited (theophylline) apical Na-H exchange. Neither Cl removal, nor the anion exchange inhibitor DIDS, nor a transepithelial bicarbonate gradient, altered propionate transport. A transepithelial pH gradient inhibited propionate secretion, but not in a manner entirely consistent with the effect of pH on the distribution of a weak electrolyte. These results suggest that there is significant segmental heterogeneity in colonic SCFA transport; that transepithelial propionate fluxes are altered by changes in pH or electroneutral Na absorption (Na-H exchange), but not by chloride removal, bicarbonate gradients or electrogenic Na absorption. Regulation of SCFA transport may be an important factor in the physiology of colonic fluid balance.

Short-chain fatty acid absorption in rabbit colon in vitro.

Short-chain fatty acids are the predominant luminal anion in the colon and are generally absorbed rapidly in vivo. However, the mechanisms of in vitro transport of short-chain fatty acids have not been fully delineated. Therefore, we examined [14C]propionate fluxes in rabbit proximal colon under short-circuit conditions. There was minimal metabolism of propionate (less than 10%), permitting accurate flux measurements using a radioisotopic tracer. In a 20 mmol/L propionate Ringer's solution at pH 7.4, there was a significant rate of propionate secretion (-0.58 +/- 0.08 microEq.cm-2.h-1). Decreasing pH to 6.8 by decreasing bicarbonate concentration in the bathing medium resulted in increases in unidirectional fluxes but no change in net transport. Reversal of propionate secretion to propionate absorption was elicited by HEPES substitution for bicarbonate at pH 6.8 or by serosal addition of epinephrine, which increases apical Na(+)-H+ exchange in this epithelium. Propionate absorption was blocked by both amiloride, an Na(+)-H+ exchange inhibitor, and ouabain. Under basal conditions, there was a concentration-dependent increase in basal unidirectional propionate fluxes with no change in net transport as the concentration of propionate increased from 10 to 60 mmol/L. In contrast, a concentration-dependent saturation of epinephrine-stimulated propionate absorption was apparent. Transepithelial propionate gradients did not yield a significant diffusion potential. These results suggest that, in rabbit proximal colon, (a) there is bidirectional diffusion of propionate, most probably in the protonated rather than the ionized form; (b) a component of propionate transport is active and linked to electroneutral Na+ absorption through apical Na(+)-H+ exchange; and (c) changes in composition of the fluid bathing the proximal colon in vitro may significantly alter both rates and direction of short-chain fatty acid transport. Regulation of transcellular active transport may play an important role in colonic short-chain fatty acid conservation.

Acid-base regulation of ion transport in rabbit ileum in vitro.

Changes in acid-base balance have a major influence on ion transport in the ileum. The goals of the present study were to delineate (a) the specific transport processes most affected by changes in acid-base metabolism, (b) the individual roles of pH, PCO2, and concentration of HCO3- in modulating ion transport, and (c) the relationship between acid-base sensitive and other ion-transport systems. Ion transport and electrical parameters were measured in rabbit ilea in vitro under short-circuit conditions with systematic variations of pH, PCO2, and concentrations of HCO3-. Increasing HCO3- concentrations, with constant PCO2 and increasing pH, caused a decrease in electroneutral Na+ and Cl- absorption. At 5 mmol/L HCO3-, net fluxes of Na+ and Cl- were 5.9 +/- 1.4 and 4.5 +/- 1.1 microEq.cm-2.h-1, while at 50 mmol/L HCO3-, net Na+ and Cl- fluxes were 0.7 +/- 0.7 and 0.2 +/- 0.6 microEq.cm-2.h-1. Transepithelial HCO3(-)-gradient experiments suggested that serosal HCO3- was the principal factor. Changes in PCO2 showed a complex biphasic response, increasing net Cl- flux as PCO2 increased from 11-30 mm Hg in 5 mmol/L HCO3-; net Na+ flux increased as PCO2 was changed from 36 to greater than 100 mm Hg in 22 mmol/L HCO3-. In contrast, increasing pH in a bicarbonate-free N-2-hydroxyethylpiperazine-N'-2 = ethane sulfonic acid buffer did not significantly alter Na+ transport. Acid-base stimulated Na+ absorption was inhibited by 10(-3) mol/L amiloride, but not by bumetanide, consistent with the involvement of Na(+)-H+ exchange rather than Na(+)-Cl- cotransport. Epinephrine did not increase Na+ absorption under acid-base stimulated conditions, but glucose did, suggesting that the rate-limiting step for electroneutral absorptive processes under these conditions occurs at the apical rather than the basolateral membrane. Combining all experiments, a significant correlation existed between net flux of Na+ and HCO3- concentration (r = -0.72, P less than 0.05) and between net flux of Na+ and pH (r = -0.68, P less than 0.01). Chloride absorption was correlated with pH (r = 0.72, P less than 0.01). These results suggest a profound regulatory role for acid-base balance in electroneutral Na(+)-Cl- transport in rabbit ileum in vitro.

Potassium secretion in response to taurodeoxycholic acid in the newborn rabbit colon.

The newborn colon fails to secrete Cl in response to concentrations of dihydroxy bile acid that cause Cl secretion in adult colonic tissue in vitro. Bile acids also cause secretion of potassium in adult tissues, but there is no information concerning bile acid effects on potassium transport in newborn colon. We mounted newborn rabbit distal colon in Ussing chambers specially designed for newborn colon and measured potassium transport. Basal potassium transport was secretory. Taurodeoxycholic acid, 100 microM, (TDC) decreased JKnet from -0.76 +/- 0.07 to -0.94 +/- 0.11 microEq cm-2 h-1, p less than 0.05, without increasing Isc. Serosal ouabain, 0.1 mM, abolished the secretory response to TDC. Mucosal Ba2+, a potassium channel blocker in many epithelia, did not inhibit K secretion. Similar serosal exposure to TDC in adult colon tissues decreased JKnet from -0.09 +/- 0.29 to -1.63 microEq cm-2 h-1, p less than 0.01, and increased Isc. We conclude that, although the chloride secretory response to dihydroxy bile acids is absent in the newborn, K secretion is elicited in the newborn, similar to the adult colon.

Regulation of bicarbonate transport in rabbit ileum: pH stat studies.

Although it is well recognized that the ileum secretes bicarbonate, understanding of the mechanisms of the transport of this ion has been limited by the inability to measure fluxes in vitro. However, by clamping the bathing fluid at a set pH using a pH stat system, accurate measurements of bicarbonate movement can be made. Bicarbonate transport in rabbit ileum in vitro was measured by simultaneously employing both the pH stat and short-circuit techniques. The role of acid-base balance was assessed by systematically altering buffer bicarbonate concentration, pH, and partial pressure of CO2 (PCO2). Bicarbonate secretion was strongly correlated with both serosal [HCO3-] (r = 0.824, P less than 0.01) and serosal pH (r = 0.793, P less than 0.01). Bicarbonate absorption was not significantly altered by mucosal [HCO3-], pH, or PCO2. Paracellular movement of bicarbonate, as assessed by voltage clamping and diffusion potential experiments, did not appear to be a major component of transcellular transport. Epinephrine stimulated bicarbonate absorption significantly, both in Cl-containing and Cl-free Ringer solution but did not alter bicarbonate secretion. Epinephrine-induced decreases in short-circuit current were correlated with enhanced bicarbonate absorption. Bicarbonate secretion was inhibited by serosal chloride and serosal bumetanide; mucosal chloride stimulated bicarbonate secretion. Mucosal chloride did not affect bicarbonate absorption. Glucocorticoids enhanced both bicarbonate absorption and secretion. These results suggest that there are discrete apical and basolateral transport mechanisms that regulate bicarbonate transport. Bicarbonate secretion may be mediated by a basolateral bumetanide-sensitive, chloride-inhibitable transporter and by an apical chloride-bicarbonate exchange process.

Steroids alter ion transport and absorptive capacity in proximal and distal colon.

Steroids are potent absorbagogues, increasing Na and fluid absorption in a variety of epithelia. This study characterizes the in vitro effects of pharmacological doses of gluco- and mineralocorticoids on transport parameters of rabbit proximal and distal colon. Treatment with methylprednisolone (MP, 40 mg im for 2 days) and desoxycortone acetate (DOCA, 12.5 mg im for 3 days) resulted in a significant increase in short-circuit current (Isc) in distal colon, suggesting an increase in basal Na absorption. Amiloride (10(-4) M) caused a significantly negative Isc in MP-treated tissue, demonstrating a steroid-induced, amiloride-insensitive electrogenic ion transport in distal colon. The effect of two absorbagogues, impermeant anions (SO4-Ringer) and amphotericin, were compared in control and steroid-treated distal colon. In controls, both absorbagogues increased Isc. Impermeant anions caused a rise in Isc in both MP and DOCA tissues, suggesting that the high rate of basal Na absorption had not caused a saturation of the Na pump. The steroid-treated colons, however, did not consistently respond to amphotericin. Amiloride inhibited the entire Isc in MP-treated distal colon that had been exposed to amphotericin; this suggested that amphotericin had not exerted its characteristic effect on the apical membrane of steroid-treated colon. In proximal colon, steroids did not alter basal rates of transport; however, epinephrine-induced Na-Cl absorption was significantly greater in MP-treated vs control (P less than 0.005). Steroids increase the absorptive capacity of both proximal and distal colon for Na, while increasing basal Na absorption only in the distal colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of upper airway carbon dioxide on ventilation and blood gases in the awake pony.

Carbon dioxide concentrations were increased during expiration in the upper one-half of the trachea, pharynx, and nasal sinuses to determine if elevation of upper airway CO2 would alter breathing or arterial blood gases in the awake pony. Carbon dioxide (100%) was injected into the midcervical trachea via a chronically implanted transcutaneous cannula during the first part of the animal's expiration. This maneuver elevated upper airway expiratory CO2 concentrations but prevented any exogenous CO2 from entering the lung and being absorbed into the arterial blood. Twelve experiments were performed on six ponies in which upper airway CO2 was elevated 2, 4, and 6% above the normal expired CO2 concentrations. Tidal volume increased in a dose dependent manner during upper airway CO2 exposure, but total ventilation was unchanged from base-line measurements made while the animal breathed room air. Arterial Po2 also increased during upper airway CO2 administration, reaching a mean value 6 Torr (1 Torr = 133.322 Pa) greater than the base-line values at the +6% CO2 exposure. We conclude that upper airway CO2 exposure alters breathing pattern slightly (increases tidal volume) and increases arterial PO2 in the awake pony.

Rabbit proximal colon: a distinct transport epithelium.

Rabbit proximal colon (PC), examined in vitro, exhibits transport characteristics distinct from distal colon. Unlike distal colon, PC does not demonstrate amiloride-inhibitable electrogenic Na absorption. Additionally, neither amphotericin nor "stimulatory" anions induce Na absorption in PC. Electrical measurements and radioisotopic flux studies under short-circuit conditions indicate that PC is a moderately leaky epithelium with a conductance (9.0 +/- 0.2 mS) midway between ileum and distal colon; under basal conditions PC has Na and Cl transport rates near zero, and 5.5 microM epinephrine (Epi) stimulates electrically silent Na-Cl coupled absorption. The mechanism of this cotransport was investigated further: Cl substitution with either sulfate or gluconate did not substantially alter Epi-enhanced Na absorption. The Epi stimulation of Cl absorption in a Na-free solution was diminished. Amiloride, 10(-3) M, inhibited Epi-enhanced Na absorption by approximately 50%. The effects of cAMP-mediated (theophylline or 8-bromo-cAMP) and Ca-mediated (ionophore A23187) secretory stimuli were examined. In the basal state, none of these agents had a consistent effect on ion transport. However, after stimulation of Na and Cl absorption by Epi, both of the cAMP-related secretagogues had a marked antiabsorptive effect on Na and Cl transport. The antiabsorptive effects of Ca ionophore A23187 were less marked. These results suggest that rabbit proximal colon a) does not share the transport properties characteristic of distal colon, b) possesses an Epi-sensitive, Na-Cl-coupled absorptive pathway, and c) responds to secretory stimuli in an antiabsorptive manner rather than by electrogenic secretion.

Cerebrovascular response to acute decreases in arterial PO2.

The purpose of these studies was to examine the time course of the cerebrovascular response to acute hypoxia in unanesthetized ponies. An electromagnetic flow transducer chronically placed on the internal carotid artery of the pony allowed continuous recording of internal carotid artery blood flow (ICBF) which has been shown to be representative of cerebral blood flow (CBF). The ponies were subjected to three levels of acute isocapnic hypoxia (PaO2 = 62, 44, and 39 mm Hg for hypoxia level I, II, and III, respectively), and the temporal and steady-state cerebrovascular response was examined. ICBF increased significantly at all three hypoxia levels (8, 25, and 40% at hypoxia I, II, and III, respectively). This increase was rapid in the two most severe levels of hypoxia, beginning within 45 s, and was complete within 90 s. The increase lagged behind the reduction in PaO2 by 24-28 s. During the very mild level of hypoxia (I), no such rapid increase in flow was observed; rather, the increase occurred only after 5 min of hypoxia. Microsphere (15 microns diameter) measurements from six ponies during the most severe level of hypoxia (III) demonstrated that CBF increased 38%. Noncerebral tissues known to be vascularly connected to the circle of Willis, and thus capable of receiving blood flow via the internal carotid artery, either did not change or increased so slightly during hypoxia that their effect on ICBF was minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Methylprednisolone increases absorptive capacity of rabbit ileum in vitro.

The effect of glucocorticoids on intestinal ion transport was studied in ileum in vitro from control and methylprednisolone (MP)-treated (40 mg im for 2 days) rabbits under the following conditions: a) basal rates of Na and Cl transport, b) the response to an individual absorptive stimulus (alanine, glucose, or epinephrine), and c) the response to a combination of the three absorptive stimuli. The results indicate that MP 1) increases basal absorption of Na and Cl and secretion of bicarbonate (as measured by residual ion flux), 2) does not alter the specific transport pathways stimulated by maximal doses of alanine, glucose, or epinephrine, but 3) significantly increases the absorptive capacity of ileum. After addition of combined alanine, glucose, and epinephrine, MP-treated ileum absorbed 15.8 mueq X cm-2 X h-1 Na (vs. 6.6 in controls, P less than 0.001) and 9.5 mueq X cm-2 X h-1 Cl (vs. 4.1 in controls, P less than 0.005). Additionally MP did not alter the Na dependence of either the short-circuit current or Cl absorption found in controls, although there appears to be a portion of residual ion flux insensitive to epinephrine inhibition. These data suggest that the MP-induced increase in absorptive capacity is due to an increase in a postapical transport step, most probably the Na pump.

Regional cerebral blood flow during hypercapnia in the anesthetized rabbit.

These experiments were designed to test the hypothesis that increases in blood flow to the lower brainstem would be greater than forebrain regions during arterial hypercapnia. Total and regional cerebral blood flow (CBF) was measured via the tracer microsphere technique in seven anesthetized New Zealand white rabbits during normocapnia (arterial PCO2 congruent to 40 torr) and hypercapnia (arterial PCO2 congruent to 80 torr). During normocapnia average CBF was 0.77 ml/min/g, and regional measurements of blood flow indicated significantly greater flow to the cerebrum (0.86 ml/min/g) than either the medulla (0.52 ml/min/g) or the pons (0.49 ml/min/g). When arterial PCO2 was increased average CBF increased 113%, and a significant linear regression was calculated for arterial PCO2 vs CBF [CBF (ml/min/g) = 0.028 PCO2 (torr) - 0.502]. The distribution of blood flow within the brain was similar to normocapnia except that blood flow to the cerebellum was now greater than any other brain region (1.97 ml/min/g for the cerebellum compared to 1.66 ml/min/g for the cerebrum). Absolute increases in blood flow to the lower brainstem were equal to or less than other areas of the brain. We conclude that ponto-medullary blood flow does not increase disproportionate to other areas of the brain during hypercapnia, but some redistribution of CBF does occur in that cerebellar blood flow increased significantly more than the cerebrum, medulla, or pons.