Jejunal Blood Flow Research Articles

Effect of the beta-adrenergic blockade on intestinal lactate production and glycogen concentration in dogs infused with hexoses

To investigate effect of beta adrenergic blockade on intestinal lactate production and glycogen concentration in dogs infused with hexoses. Experiments were carried out on 35 fasted male anaesthetized dogs weighing between 9 and 16kg. The animals were divided into 7 (5 dogs per group) groups. Group I dogs served as control and infused with normal saline, groups II-IV were intravenously infused with glucose (1.1mg/kg/min), fructose (1.1mg/kg/min) and galactose (1.1mg/kg/min) respectively while groups V-VII animals were pretreated with propranolol (0.5mg/kg) and were infused with glucose, fructose or galactose respectively. A vein draining the proximal segment of the jejunum was cannulated along with right and left femoral arteries and veins. Glucose uptake was calculated as the product of jejunal blood flow and the difference between arterial and venous glucose levels (A-V glucose), part of the jejunum tissue was homogenized for estimation of glycogen concentration, and plasma lactate was assayed using lactate colorimetric kit. The result showed significant increase in venous lactate production in response to glucose (78.30±4.57mg/dL), fructose (60.72±1.82mg/dL) and galactose (71.70±1.30mg/dL) when compared with the control group (51.75±1.32mg/dL) at (p<0.05) with no significant difference in animals pretreated with propranolol. There was no significant difference in glycogen concentration (p>0.05) in animals infused with hexoses only compared with propanolol pretreated group. Results suggests that one of the possible fates of the enormous amount of glucose taken up by the intestine is conversion to lactate and not glycogen and β-adrenergic receptor does not affect it.

Chronic treatment with rofecoxib but not ischemic preconditioning of the myocardium ameliorates early intestinal damage following cardiac ischemia/reperfusion injury in rats

There is some recent evidence that cardiac ischemia/reperfusion (I/R) injury induces intestinal damage within days, which contributes to adverse cardiovascular outcomes after myocardial infarction. However, it is not clear whether remote gut injury has any detectable early signs, and whether different interventions aiming to reduce cardiac damage are also effective at protecting the intestine. Previously, we found that chronic treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), limited myocardial infarct size to a comparable extent as cardiac ischemic preconditioning (IPC) in rats subjected to 30-min coronary artery occlusion and 120-min reperfusion. In the present study, we aimed to analyse the early intestinal alterations caused by cardiac I/R injury, with or without the above-mentioned infart size-limiting interventions. We found that cardiac I/R injury induced histological changes in the small intestine within 2 h, which were accompanied by elevated tissue level of COX-2 and showed positive correlation with the activity of matrix metalloproteinase-2 (MMP-2), but not of MMP-9 in the plasma. All these changes were prevented by rofecoxib treatment. By contrast, cardiac IPC failed to reduce intestinal injury and plasma MMP-2 activity, although it prevented the transient reduction in jejunal blood flow in response to cardiac I/R. Our results demonstrate for the first time that rapid development of intestinal damage follows cardiac I/R, and that two similarly effective infarct size-limiting interventions, rofecoxib treatment and cardiac IPC, have different impacts on cardiac I/R-induced gut injury. Furthermore, intestinal damage correlates with plasma MMP-2 activity, which may be a biomarker for its early diagnosis.

Morbid obesity and type 2 diabetes alter intestinal fatty acid uptake and blood flow

AimsBariatric surgery is the most effective treatment to tackle morbid obesity and type 2 diabetes, but the mechanisms of action are still unclear. The objective of this study was to investigate the effects of bariatric surgery on intestinal fatty acid (FA) uptake and blood flow.Materials and MethodsWe recruited 27 morbidly obese subjects, of whom 10 had type 2 diabetes and 15 were healthy age‐matched controls. Intestinal blood flow and fatty acid uptake from circulation were measured during fasting state using positron emission tomography (PET). Obese subjects were re‐studied 6 months after bariatric surgery. The mucosal location of intestinal FA retention was verified in insulin resistant mice with autoradiography.ResultsCompared to lean subjects, morbidly obese subjects had higher duodenal and jejunal FA uptake (P < .001) but similar intestinal blood flow (NS). Within 6 months after bariatric surgery, obese subjects had lost 24% of their weight and 7/10 diabetic subjects were in remission. Jejunal FA uptake was further increased (P < .03). Conversely, bariatric surgery provoked a decrease in jejunal blood flow (P < .05) while duodenal blood flow was preserved. Animal studies showed that FAs were taken up into enterocytes, for the most part, but were also transferred, in part, into the lumen.ConclusionsIn the obese, the small intestine actively takes up FAs from circulation and FA uptake remains higher than in controls post‐operatively. Intestinal blood flow was not enhanced before or after bariatric surgery, suggesting that enhanced intestinal FA metabolism is not driven by intestinal perfusion.

Effects of meal and incretins in the regulation of splanchnic blood flow.

ObjectiveMeal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions.DesignA non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed.MethodsEffects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with 15O-water and 15O-carbon monoxide, respectively.ResultsIngestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1.ConclusionTogether, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow.

Effect of age on gastrointestinal and hepatic first-pass effects of levodopa in rats

Presystemic elimination of levodopa (20 mg kg-1) has been studied in 5- to 104-week-old male Wistar rats. The gastrointestinal and hepatic contribution to the overall first-pass effect was estimated separately after the drug had been administered intravenously, orally and intraportally. The contribution of the gut to the overall first-pass effect of this drug was greater than that of the liver in any age-group of the rats. Both the overall and intestinal first-pass effects of levodopa were greatest in 11-week-old rats and relatively small in both young (between weeks 5 and 7) and aged (between weeks 52 and 104) rats. In contrast, the hepatic first-pass effect did not show any significant age-dependent change. Age-related change in the jejunal blood flow could not explain the unique age-dependence in the intestinal first-pass metabolism of levodopa. However, the present age-dependence in the oral systemic availability of this drug between adult (11 weeks) and aged (52 to 104 weeks) rats was found to be similar to the tendency that has been reported between normal adult subjects and aged patients with Parkinson's disease.

EFFECTS OF LOW ABDOMINAL BLOOD FLOW AND DOBUTAMINE ON BLOOD FLOW DISTRIBUTION AND ON THE HEPATIC ARTERIAL BUFFER RESPONSE IN ANAESTHETIZED PIGS

Low cardiac output impairs the hepatic arterial buffer response (HABR). Whether this is due to low abdominal blood flow per se is not known. Dobutamine is commonly used to increase cardiac output, and it may further modify hepatosplanchnic and renal vasoregulation. We assessed the effects of isolated abdominal aortic blood flow changes and dobutamine on hepatosplanchnic and renal blood flow. Twenty-five anesthetized pigs with an abdominal aorto-aortic shunt were randomized to 2 control groups [zero (n = 6) and minimal (n = 6) shunt flow], and 2 groups with 50% reduction of abdominal blood flow and either subsequent increased abdominal blood flow by shunt reduction (n = 6) or dobutamine infusion at 5 and 10 microg kg(-1) min(-1) with constant shunt flow (n = 7). Regional (ultrasound) and local (laser Doppler) intra-abdominal blood flows were measured. The HABR was assessed during acute portal vein occlusion. Sustained low abdominal blood flow, by means of shunt activation, decreased liver, gut, and kidney blood flow similarly and reduced local microcirculatory blood flow in the jejunum. Shunt flow reduction partially restored regional blood flows but not jejunal microcirculatory blood flow. Low-but not high-dose dobutamine increased gut and celiac trunk flow whereas hepatic artery and renal blood flows remained unchanged. Neither intervention altered local blood flows. The HABR was not abolished during sustained low abdominal blood flow despite substantially reduced hepatic arterial blood flow and was not modified by dobutamine. Low-but not high-dose dobutamine redistributes blood flow toward the gut and celiac trunk. The jejunal microcirculatory flow, once impaired, is difficult to restore.

Systemic and regional haemodynamics in pigs with acute liver failure and the effect of albumin dialysis

Objective. Acute liver failure (ALF) is haemodynamically characterized by a hyperdynamic circulation. The aims of this study were to investigate the systemic and regional haemodynamics in ALF, to measure changes in nitric oxide metabolites (NOx) and to evaluate whether these haemodynamic disturbances could be attenuated with albumin dialysis. Material and methods. Norwegian Landrace pigs (23–30 kg) were randomly allocated to groups as controls (sham-operation, n=8), ALF (hepatic devascularization, n=8) and ALF + albumin dialysis (n=8). Albumin dialysis was started 2 h after ALF induction and continued for 4 h. Systemic and regional haemodynamics were monitored. Creatinine clearance, nitrite/nitrate and catecholamines were measured. A repeated measures ANOVA was used to analyse the data. Results. In the ALF group, the cardiac index increased (PGT<0.0001), while mean arterial pressure (PG=0.02) and systemic vascular resistance decreased (PGT<0.0001). Renal resistance (PG=0.04) and hind-leg resistance (PGT=0.003) decreased in ALF. There was no difference in jejunal blood flow between the groups. ALF pigs developed renal dysfunction with increased serum creatinine (PGT=0.002) and decreased creatinine clearance (P=0.02). Catecholamines were significantly higher in ALF, but NOx levels were not different. Albumin dialysis did not attenuate these haemodynamic or renal disturbances. Conclusions. The haemodynamic disturbances during the early phase of ALF are characterized by progressive systemic vasodilatation with no associated changes in metabolites of NO. Renal vascular resistance decreased and renal dysfunction developed independently of changes in renal blood flow. After 4 h of albumin dialysis there was no attenuation of the haemodynamic or renal disturbances.

Intestinal injury after thoracic aortic cross-clamping in the pig

Background The mucosal surface epithelium is an essential part of the functional intestinal barrier, but its structural response to ischemia/reperfusion is only partly characterized. The purpose of this study was to provide a detailed morphological evaluation of intestinal surface epithelium after aortic cross-clamping. Material and methods Pigs were subjected to thoracic aortic cross-clamping for 60 min and subsequent reperfusion for 120 min. Tissue blood flow and high-energy phosphates were measured with microspheres and HPLC, respectively. Urinary excretion of 14C polyethylene glycol (MW 4000 Da) (PEG-4000), loaded into an intestinal loop, provided an index of intestinal permeability. Results Jejunal blood flow was restored at 10 min after aortic declamping. Denudation of the basement membrane of the intestinal villi tips, as a consequence of epithelial shedding, increased markedly during the initial 60 min of reperfusion ( P = 0.002). During the following 45 min, the denuded basement membrane was partly covered with low cuboidal and squamous-shaped cells extending lamellipodia over a wavy basement membrane. Restoration of ATP at 60 min after aortic declamping correlated inversely to the extent of denuded basement membrane ( r = 0.75, P = 0.032). Permeability of PEG-4000 increased markedly after aortic declamping and was linearly correlated to the area of denuded basement membrane ( r = 0.87, P = 0.01). Conclusions Reperfusion for 2 h after aortic cross-clamping is associated with initial aggravation of ischemia-induced injury in the porcine jejunum, but thereafter with restitution of the surface epithelium. Restoration of ATP may be important to avoid intestinal injury after ischemia. Increased permeability of a macromolecule in response to reperfusion is closely correlated to injury of the surface epithelium.

Local metabolic effects of dopexamine on the intestine during mesenteric hypoperfusion.

This self-controlled experimental study was designed to test the hypothesis that dopexamine, a synthetic catecholamine that activates dopaminergic (DA-1) and beta2-adrenergic receptors, improves oxygenation in the jejunal mucosa during intestinal hypotension. In six normoventilated barbiturate-anesthetized pigs, controlled reductions in superior mesenteric arterial pressure (PSMA) was obtained by an adjustable clamp around the artery. Dopexamine infusions (0.5 and 1.0 microg.kg(-1).min(-1)) were administered at a freely variable PSMA (i.e., with the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. We continuously measured superior mesenteric venous blood flow (QMES; transit-time ultrasonic flowmetry), jejunal mucosal perfusion (laser Doppler flowmetry), and tissue oxygen tension (PO2TISSUE; microoximetry). Jejunal luminal microdialysate of lactate, pyruvate, and glucose were measured every 5 min. Measurements of mucosal PCO2 (air tonometry), together with blood sampling and end-tidal PCO2 measurements, enabled calculations of pHi and PCO2 gap. Dopexamine reduced mesenteric vascular resistance and increased QMES at a PSMA of 50 mmHg and 30 mmHg. At a PSMA of 30 mmHg, dopexamine increased mesenteric oxygen delivery but did not influence mesenteric oxygen uptake or extraction. In this situation, dopexamine had no beneficial effect on jejunal mucosal blood flow. On the contrary, dopexamine increased mesenteric net lactate production and PCO2 gap, whereas PO2TISSUE and pHi decreased. Jejunal luminal microdialysate data demonstrated an increased lactate concentration and a pattern of decreased glucose concentration and increased luminal lactate-pyruvate ratio. These negative metabolic effects of dopexamine should be taken into account in situations of low perfusion pressures.

Effects of three different resuscitation regimens on jejunal tissue oxygen supply after hemorrhagic shock

In this study we evaluated effects of blood (B; n = 7), gelatine (G; n = 8) and Ringer's lactate (R; n = 8) resuscitation on jejunal microvascular blood flow (PU), tissue microvascular hemoglobin oxygen saturation (HbO2t) and jejunal mucosal tissue oxygen tension (PO2muc) after severe haemorrhage (50% of estimated blood volume) in pigs.

Effects of intraluminal distention and decompression on microvascular permeability and hemodynamics of the equine jejunum.

To determine whether intraluminal distention and subsequent decompression of the equine jejunum affects intestinal blood flow, hemodynamics, and microvascular permeability. 5 healthy adu t horses. Horses were anesthestized and underwent exploratory laparotomy. Two jejunal segments were identified as sham-operated or instrumented segments. After baseline values were obtained, intraluminal distention was created in the experimental segment to induce an ntraluminal pressure of 18 cm H2O. After 120 minutes of distention, the intestine was decompressed for 120 minutes. Mesenteric blood flow, oxygen delivery, oxygen consumption, microvascular permeability, wet weight-to-dry weight ratio, neutrophil infiltration, and vascular resistance were determined and comparisons made among control, sham-operated, and experimental segments. Mean jejunal blood flow was 21.4 ml/min per kg. There was a significant decrease in mesenteric bood flow to the distended intestine (13.4 ml/min per kg). Blood flow increased significantly during the decompression period (340% of baseline blood flow). Intraluminal distention and subsequent decompression resulted in a significant increase in microvascular permeability, as determined by the osmotic reflection coefficient. Oxygen delivery and oxygen content decreased significantly during the distention period and increased during decompression. Morphologic evaluation revealed a significant increase in edema and neutrophil infiltration after distention and decompression, compared with results for the sham-operated or control segments. Intraluminal distention and decompression of the equine jejunum results in low-flow ischemia and edema, which may contribute to adhesions and ileus in the postoperative period after surgery for obstructions of the small intestines.

Decreases in organ blood flows associated with increases in sublingual P CO 2 during hemorrhagic shock

Earlier studies demonstrated that not only the stomach but also the esophageal wall served as an appropriate site for estimating the severity of circulatory shock by using tonometric methods. We then conceived of the option of sublingual tonometry. In the present study, we tested the hypothesis that the changes in sublingual PCO2 serve as indicators of decreases in blood flow to sublingual and visceral tissue. In Sprague-Dawley rats, sublingual PCO2 increased from 50 to 127 Torr and arterial blood lactate increased from 0.9 to 11.2 mmol/l during bleeding. Sublingual blood flow simultaneously decreased to approximately 32% of preshock values. After reinfusion of shed blood, organ blood flows and sublingual PCO2 were promptly restored to near-baseline values. There were corresponding decreases in blood flows in the tongue, stomach, jejunum, colon, and kidneys during hemorrhagic shock. Increases in sublingual PCO2 were highly correlated with decreases in sublingual blood flow (r = 0.80), tongue blood flow (r = 0.81), gastric blood flow (r = 0.74), jejunal blood flow (r = 0.65), colon blood flow (r = 0.80), and renal blood flow (r = 0.75). Unbled control animals demonstrated no significant changes. Therefore, we anticipate that sublingual tonometry will provide a useful, noninvasive alternative for monitoring visceral PCO2.

Changes in hemodynamics in jejunal flaps of rabbits due to ischemia, venous congestion, and reperfusion as measured by means of colored microspheres.

The effect on the jejunal hemodynamics of restoration of blood flow of the jejunal artery or vein in the free jejunal flap has not yet been elucidated. In the present study, a model of ischemia and reperfusion in the jejunal flap of rabbits, and that of venous congestion and reperfusion, were prepared. Jejunal blood flow was measured by means of colored microspheres, and changes in jejunal blood flow were analyzed. Three segmental jejunal flaps were designed on each rabbit (n = 16), with one artery and one vein kept intact. Arterial clamp and venous clamp groups were prepared with a control group in which there was no clamping. After clamping for 5 minutes (n = 7), the jejunal blood flow of the arterial clamp group decreased to 1.6 percent of that of the control group (p = 0.0002), and that of the venous clamp group decreased to 31.2 percent of that of the control group (p = 0.0041). At 5 minutes after release of clamping, the jejunal blood flow of the arterial clamp group recovered to only 74.1 percent of that of the control group, with no consistent tendency; that of the venous clamp group recovered to 45.9 percent of that of the control group (p = 0.0194), with an increase of only 14.7 percent over that of the clamped jejunal blood flow group. Thus, injury of the jejunal hemodynamics in the venous clamp group had already begun in response to clamping for 5 minutes. After clamping for 30 minutes (n = 9), the jejunal blood flow of the arterial clamp group decreased to 4.3 percent of that of the control group (p = 0.0060), and that of venous clamp group decreased to 12.5 percent of that of the control group (p = 0.0106). At 5 minutes after release of clamping, jejunal blood flow of the arterial clamp group recovered to 171.0 percent of that of the control group (p = 0.0295), and that of venous clamp group recovered to 41.7 percent of that of the control group (p = 0.0276). Jejunal blood flow of the arterial clamp group recovered to 409.7 percent of that of the venous clamp group (p < 0.0001). When measurement of jejunal blood flow was repeated twice after changing the color of microspheres, jejunal blood flow of the second measurement was approximately 24 percent greater in mean value than that of the first measurement. The histologic results of the jejunum of the arterial clamp group clamped for 30 minutes showed no injury, which was similar to the results of the control group. The jejunum of the venous clamp group clamped for 5 minutes showed injury with severe hemorrhage in the lamina propria, and irreversible injury 30 minutes thereafter, with massive hemorrhage in all layers of the jejunal wall. In conclusion, as microcirculatory hemodynamics and histologic results of the jejunum demonstrated evidence of injury even by venous congestion for 5 minutes, restoration of blood flow of the free jejunal flap must be started from the jejunal vein.

The effects of progressive anemia on jejunal mucosal and serosal tissue oxygenation in pigs.

Anemia may promote intestinal hypoxia. We studied the effects of progressive isovolemic hemodilution on jejunal mucosal (Po2muc), and serosal tissue oxygen tension (Po2ser, Clark-type surface electrodes), mucosal microvascular hemoglobin oxygen saturation (Hbo2muc), and hematocrit (Hctmuc; tissue reflectance spectophotometry) in a jejunal segment. Twelve domestic pigs were anesthetized, paralyzed, and mechanically ventilated. Laparatomy was performed, arterial supply of a jejunal segment isolated, and constant pressure pump perfused. Seven animals were progressively hemodiluted to systemic hematocrits (Hctsys) of 20%, 15%, 10%, and 6%. Baseline for Po2muc, Po2ser and Hbo2muc was 23.5 +/- 2.1 mm Hg, 57.5 +/- 4 mm Hg, and 47.0% +/- 6.4% which were not different from the five controls. Despite a significant increase in jejunal blood flow, jejunal oxygen delivery decreased and oxygen extraction ratio increased significantly at Hctsys 10% and 6%. Po2ser decreased significantly below or at Hctsys of 15%, whereas Po2muc and Hbo2muc were maintained to Hctsys of 10%, but less than 10% Hbo2muc and mesenteric venous pH decreased significantly, implying that physiological limits of jejunal microvascular adaptation to severe anemia were reached. Decrease of Hctmuc was less pronounced than Hctsys. In conclusion, redistribution of jejunal blood flow and an increase in the ratio of mucosal to systemic hematocrit are the main mechanisms maintaining mucosal oxygen supply during progressive anemia.

Differential effects of an infusion of endotoxin on proximal and distal feline jejunal permeability

The effects of an intravenous infusion of endotoxin (750 μg/kg) or an equal volume of saline solution (control) on the proximal and distal jejunal permeability and blood flow were evaluated in cats. In 8 cats, proximal and distal jejunal segments were isolated and mucosal clearance of 51Cr-ethylenediaminetetraacetic acid (EDTA) was measured. The mucosal clearance in the distal loop was not altered by endotoxin infusion in 6 cats given endotoxin or 2 cats given saline solution. In 6 cats given endotoxin, the proximal jejunal segment exhibited a 10-fold increase in mucosal permeability. In contrast, mucosal clearance remained stable in the proximal jejunal loop in 2 cats infused with saline solution. In a second group of 13 cats (7 cats infused with endotoxin; 6 cats infused with saline solution), blood flow to the proximal and distal segments was measured. Either endotoxin (n = 7) or saline solution (n = 6) did not significantly alter blood flow to the proximal and distal jejunum in these experiments. Samples of proximal and distal jejunum were collected from 12 cats (6 cats infused with endotoxin and 6 cats infused with saline solution). There was significantly more epithelial necrosis in the endotoxin treated cats than in the saline treated cats. Neutrophil infiltration was greater in the jejunal segments of endotoxin treated cats than in the jejunal segments of saline treated cats. In the endotoxin treated cats, there was significantly greater necrosis in the proximal jejunal segment than in the distal jejunal segment. There were no significant differences in numbers of neutrophils in the proximal and distal jejunal segments. These results demonstrate that the proximal jejunum is more sensitive to endotoxin-induced increases in mucosal permeability than is the distal jejunum. The increases in mucosal permeability in the proximal jejunum were not accompanied by significant reductions in jejunal arterial blood flow. Endotoxemia induced neutrophil infiltration to the proximal and distal jejunum.

Exposure to ionizing radiation alters vasoreactivity in rat jejunum ex vivo.

The effect of ionizing radiation on jejunal blood flow was investigated in rats receiving whole-body exposure to 10 Gy gamma-radiation. Irradiation resulted in increased myeloperoxidase activity, indicative of neutrophil infiltration, and prostaglandin E2 synthesis by 2 h post-irradiation, but had no effect on leukotriene B4 synthesis. In ex vivo intestinal chamber studies, exposure to radiation reversed the mucosal-submucosal blood flow changes elicited by intravenous administration of leukotriene C4 (1 microgram.kg-1.min-1 for 10 min) or endothelin 1 (1 microgram.kg-1.min-1 for 5 min), but not that elicited by topical capsaicin (100 or 640 microM), as measured by laser Doppler flowmetry. The effect of radiation on vascular responses to leukotriene C4, but not those to endothelin 1, was reversed by pretreatment of the rats with the cyclooxygenase inhibitor, indomethacin (5 mg/kg). There was no significant effect of irradiation on mean arterial pressure or on ion or protein effluxes into the chamber bathing solution, nor did irradiation alter transmural potential difference. These studies point to altered responsiveness of the jejunal mucosal-submucosal vasculature shortly after exposure to ionizing radiation. Changes in function could reflect the onset of an acute inflammatory response, and appear to have cyclooxygenase-dependent and -independent components.

Effects of indomethacin on jejunal mucosal blood flow in the infant rat

Effects of indomethacin on jejunal mucosal blood flow in the infant rat

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98 +/- 12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42 +/- 9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27 +/- 5% and increased AP by 37 +/- 11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42 +/- 7%, 65 +/- 12%, and 58 +/- 8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.v.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.

Effects of cardiopulmonary bypass on gut blood flow, oxygen utilization, and intramucosal pH

Studies documenting rises in endotoxin after cardiopulmonary bypass (CPB) have postulated gut mucosal hypoperfusion. We have investigated alterations in jejunal blood flow by laser Doppler flow measurement, intramucosal pH (pHi) by tonometry, and oxygen utilization in a canine model of hypothermic CPB (n = 11 dogs). After 10 minutes of hypothermic CPB, despite no major reduction in superior mesenteric artery flow, mucosal laser Doppler flow decreased to −38.2% ± 9.3% of levels obtained before bypass ( p = 0.008) and serosal laser Doppler flow, to −47.3% ± 11.4% ( p = 0.006). During the hypothermic phase, mesenteric oxygen consumption fell from 0.18 ± 0.01 to 0.098 ± 0.01 mL · min −1 · kg −1 ( p = 0.005), and mesenteric oxygen delivery fell from 1.97 ± 0.39 to 1.14 ± 0.12 mL · min −1 · kg −1 ( p = 0.05). There was no change in jejunal pHi. During the rewarming phase, there was a substantial increase in mucosal laser Doppler flow, peaking at +69.8% ± 15.2% ( p = 0.03), whereas serosal laser Doppler flow returned to values seen prior to CPB (−16.4% ± 21.5%; p = 0.25). These changes coincided with a surge in oxygen consumption (0.33 ± 0.042 mL · min −1 · kg −1; p = 0.009), white mesenteric oxygen delivery remained depressed at 1.09 ± 0.12 mL · min −1 · kg −1 ( P = 0.04). Jejunal pHi fell from a value of 7.36 ± 0.04 before CPB to 7.12 ± 0.07 ( p = 0.02), thus indicating mucosal hypoxia. During the rewarming phase of hypothermic CPB, there is a disparity between mesenteric oxygen consumption and oxygen delivery with villus tip ischemia; these findings may explain the pathophysiology of endotoxemia during CPB.

L-NAME, nitric oxide and jejunal motility, blood flow and oxygen uptake in dogs.

1. The effects of the inhibitor of nitric oxide (NO) synthesis, NG-nitro-L-arginine methyl ester (L-NAME), on systemic arterial blood pressure and jejunal motility, blood flow, and oxygen uptake have been investigated in anaesthetized dogs. 2. L-NAME (cumulative doses of 0.1-20 mg kg-1, i.v.) dose-dependently increased blood pressure and jejunal motility and decreased heart rate. The maximal response of these three variables occurred at doses, 3, 10 and 10 mg kg-1, respectively. L-NAME (cumulative doses of 0.5-5 mg kg-1) also dose-dependently induced jejunal vasoconstriction. The jejunal vascular resistance returned to control values as the cumulative doses reached 10 and 20 mg kg-1, which corresponded to the maximal increase in jejunal motility. 3. A single intravenous injection of L-NAME (10 mg kg-1) produced a prompt increase in blood pressure, which lasted for at least 50 min. 4. L-NAME (10 mg kg-1) produced a progressive rise in jejunal motility reaching its maximum (47 +/- 6 mmHg) 15 min after the administration, and lasting for 40-50 min. Both the basal lumen pressure and the amplitude of rhythmic contractions increased during this period. 5. L-NAME (10 mg kg-1) produced a triphasic change in jejunal vascular resistance and blood flow measured by timed collection of venous outflow. The blood flow decreased initially (-43% at 5 min), increased (+35%) and returned to control value between 15 and 35 min, then decreased (-35%) 40-50 min post-infusion. Jejunal vascular resistance reflected the blood flow response (+88% at both 5 and 50 min). The time during which the reversal of the vasoconstriction occurred (15-35 min) corresponded to the time of marked increase in motility, and was accompanied by a significant increase in jejunal oxygen uptake (+ 18%).6. The L-NAME-induced increase in motility was prevented by L-arginine (1 g kg-1, i.v.) but not by D-arginine pretreatment. The interim (15-35 min) changes in jejunal blood flow, vascular resistance and oxygen uptake were also prevented by L-arginine pretreatment.7. L-Arginine pretreatment attenuated L-NAME-induced hypertension for 5 min.8. The L-NAME-induced increases in jejunal vascular resistance and motility were inhibited by either local intra-arterial infusion of L-arginine (32 mM local arterial blood concentration) or topical application of 2 MicroM nitroglycerin. Infusion of D-arginine (32 mM local arterial blood concentration) had no such effect.9. The L-NAME-induced increase in blood pressure was not the mechanism by which jejunal motility was increased, because similar increases in blood pressure by mefenamate (10 mg kg-1, i.v.) had no such effect.10. Thus, inhibition of nitric oxide synthesis by L-NAME increased jejunal motility and vascular resistance and the marked increase in motility can abolish or reverse the vasoconstriction. Endogenous nitric oxide may play a role in regulating motility and blood flow in the resting canine jejunum.