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PubMed2006

Phosphorylation of endothelial nitric-oxide synthase is diminished in mesenteric arteries from septic rabbits depending on the altered phosphatidylinositol 3-kinase/Akt pathway: reversal effect of fluvastatin therapy.

Endothelial dysfunction plays a crucial role in the pathophysiology of sepsis. Alterations in endothelial nitric-oxide synthase (eNOS) may contribute to the impaired endothelial function. We investigated whether the regulatory mechanism for eNOS phosphorylation and activation is altered in a rabbit lipopolysaccharide-induced septic model. Following induction of sepsis, a time-dependent marked reduction in eNOS phosphorylation was observed in mesenteric arteries, with a significant decrease in eNOS expression. Likewise, Akt phosphorylation was progressively and profoundly reduced, although total Akt remained unchanged. Furthermore, the amounts of the two subunits of phosphatidylinositol 3-kinase (PI3-K) in the membranous pool were diminished without changes in the total amount of the PI3-K heterodimer, indicating a decrease in translocation to the membranes. In vivo treatment with fluvastatin restored the decrease in eNOS phosphorylation in septic mesenteric vessels. This was possibly the result of the recovery of Akt phosphorylation. Treatment with the PI3-K inhibitor wortmannin partially inhibited the fluvastatin-induced increases in phosphorylation of Akt and eNOS, and the decrease in translocation of PI3-K heterodimer to the membranes during sepsis was slightly improved by fluvastatin. Sepsis-induced impairment of eNOS expression was also nearly normalized by fluvastatin. It is noteworthy that rabbits treated with fluvastatin exhibited a dramatic improvement in sepsis survival. The present results showed vascular abnormalities of the PI3-K/Akt pathway involved in the impairment of eNOS phosphorylation and activation in sepsis. We also suggest that fluvastatin would ameliorate vascular endothelial dysfunction, in part, presumably via its recovery effect on Akt-dependent eNOS phosphorylation. It may be potentially useful for therapy of sepsis.

Androstadienes↗

PubMed1990

Lactated Ringer's solution versus 3% albumin for resuscitation of a lethal intestinal ischemic shock in rats.

Previously, we determined that a colloid concentration of about 3% was optimal for resuscitation of lethal ischemic intestinal shock model in rats. Maximal volumes of lactated Ringer's solution (RL) alone only expanded plasma volume (PV) to 80% of preshock level, while increasing volumes of 3% albumin (ALB) in RL linearly expanded PV up to twice the preshock level. This study compares the effect of RL and ALB on survival and PV in 175 rats. The solutions were given in volumes to induce suboptimal PV expansion, requiring 10 and 44 ml/100 g body weight (bwt) of ALB and RL, respectively. ALB (20 ml/100 g bwt) was then given to induce a PV above the preshock level. Shock was induced by exteriorizing the small intestine and occluding the superior mesenteric vessels for 75 min. PV was estimated using Hct. Therefore, infusions were given continuously for 6 h in volumes that maintained a stable Hct. Untreated shocked animals developed hemoconcentration (Hct 58%) corresponding to a PV of 56% of preshock level, with 2% (1/53) of the animals surviving 24 h. The maximum effect of RL (44 ml/100 g bwt) was to expand PV to 80% of preshock level, with a 32% 24-h survival rate. Only 23% as much ALB (10 ml/100 g bwt) was needed to induce similar blood volume expansion with 24-h survival rate of 46%. When the larger volume of ALB (20 ml/100 g bwt) was used, PV expanded to 115% of preshock level, and 24-h survival to 76%, greater than that achieved with either the smaller volume of ALB or RL alone (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Resting intracellular pH in mesenteric resistance arteries from spontaneously hypertensive and Wistar-Kyoto rats: effects of amiloride and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid.

In order to investigate the membrane-located mechanisms that control intracellular pH in resistance arteries, mesenteric vessels from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 5 weeks of age were mounted in a myograph and loaded with 2',7'-bis(carboxyethyl)5,6-carboxyfluorescein (BCECF). Resting intracellular pH was studied over 10 min in the presence of amiloride (1 mmol/l), or 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS; 0.2 mmol/l). In the presence of DIDS, there was no significant difference in the resulting fall in intracellular pH over 10 min between rat strains. However, in the presence of amiloride there was a significantly greater fall in intracellular pH in SHR (P less than 0.001). These data indicate that in the resting state Na(+)-H+ exchange is increased in SHR resistance arteries at the time when blood pressure is rising and vascular remodelling is taking place.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2001

Oscillation in the activities of MEK/ERK1/2 during cardiopulmonary bypass in pigs.

BACKGROUND: Because cardiopulmonary bypass (CPB) is associated with edema and vasoreactive dysfunction and ERK1/2 pathway is involved in vascular contractility and permeability, a time course study was performed to monitor MEK/ERK1/2/Elk-1 activities during CPB. METHODS: Pigs were subjected to normothermic CPB for 90 minutes followed by post-CPB perfusion for 180 minutes. Atrial myocardium was sampled before CPB, 5 minutes after CPB onset, 5 minutes after weaning from CPB, and at the end of post-CPB. Skeletal muscle and mesenteric vessels samples were harvested before CPB, 5 minutes after CPB institution, and every 30 minutes thereafter to the end of post-CPB. Samples were analyzed by immunoblotting and immunofluorescence microscopy with the use of specific antibodies against active (phosphorylated) forms of ERK1/2, MEK1/2, and Elk-1. RESULTS: Pigs that were subjected to CPB showed an increase in phospho-ERK1/2 after 30 minutes of CPB, followed by a decrease after 90 minutes. Another phosphorylation peak was observed 30 to 60 minutes of post-CPB, followed by a decrease to below baseline at the end of reperfusion. MEK1/2 and Elk-1 activation profiles paralleled ERK1/2 activity peaks. Control samples showed no significant increase above basal levels. CONCLUSIONS: Activation of MEK/ERK1/2/Elk-1 pathways closely follows major CPB surgical manipulations (institution and termination) and could be related to morbidity during and after CPB.

Animals↗

PubMed2005

Mesenteric venous thrombosis with transmural intestinal infarction: a population-based study.

OBJECTIVE: To determine the cause-specific mortality from and incidence of transmural intestinal infarction caused by mesenteric venous thrombosis (MVT) in a population-based study and to evaluate the findings at autopsy by evaluating autopsies and surgical procedures. METHODS: All clinical (n = 23,446) and forensic (n = 7569) autopsies performed in the city of Malmö between 1970 and 1982 (population 264,000 to 230,000) were evaluated. The autopsy rate was 87%. The surgical procedures were performed in 1970, 1976, and 1982. Autopsy protocols coded for intestinal ischemia or mesenteric vessel occlusion, or both, were identified in a database. In all, 997 of 23,446 clinical and 9 of 7,569 forensic autopsy protocols were analyzed. A 3-year sample of the surgical procedures, comprising 21.3% (11,985 of 56,251) of all operations performed during the entire study period, was chosen to capture trends of diagnostic and surgical activity. In a nested case-control study within the clinical autopsy cohort, four MVT-free controls, matched for gender, age at death, and year of death were identified for each fatal MVT case to evaluate the clinical autopsy findings. RESULTS: Four forensic and 23 clinical autopsies demonstrated MVT with intestinal infarction. Seven patients were operated on, of whom six survived. The cause-specific mortality ratio was 0.9:1000 autopsies. The incidence was 1.8/100,000 person years. At autopsy, portal vein thrombosis and systemic venous thromboembolism occurred in 2 of 3 and 1 of 2 of the cases, respectively. Obesity was an independent risk factor for fatal MVT (P =.021). CONCLUSIONS: The estimated incidence of MVT with transmural intestinal infarction was 1.8/100,000 person years. Portal vein thrombosis, systemic venous thromboembolism and obesity were associated with fatal MVT.

Adult↗

PubMed1987

The influence of dietary marine oil (Polepa) and evening primrose oil (Efamol) on prostaglandin production by the rat mesenteric vasculature.

The interactions of n-6 and n-3 fatty acids on prostaglandin metabolism in the isolated rat mesenteric vessels were studied. Sprague-Dawley rats (200-220 g) were fed for two weeks a fat-free semi-synthetic diet supplemented with 10% by weight of different combinations of Evening Primrose Oil (Efamol), a rich source of linoleic acid (LA) and gamma-linolenic acid (GLA), the immediate precursor of dihomo-gamma-linolenic acid (DGLA), and Polepa (POL), a marine oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The combinations of supplement were as follows: 9% Efamol - 1% POL, 8% Efamol - 2% POL, 7% Efamol - 3% POL, 6% Efamol - 4% POL, 5% Efamol - 5% POL. The outflow of thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), PGE2, and PGE1 was decreased in relation to the proportion of marine oil in the diet, except for the group which received 8% Efamol - 2% POL, and which showed an increase in 6-keto-PGF1 alpha, PGE2, and PGE1. The decrease in TxB2 was much greater than those of 6-keto-PGF1 alpha or PGE2, while PGE1 followed the same pattern as prostacyclin and PGE2. These results suggest that n-3 fatty acids, at high concentrations, inhibits conversion of both DGLA and AA to eicosanoids. Low concentrations of fish oil may, in contrast, increase formation of desirable 1 and 2 series eicosanoids.

Administration, Oral↗

PubMed1975

Intestinal necrosis and perforation after renal transplantation.

An acute intestinal disorder occurred in seven patients soon after renal transplantation. The disorder was characterized initially by massive abdominal distention with progression to multiple bowel perforations in three patients and extensive bowel necrosis in two. Surgical manipulation did not appear to be the cause since the transplants were performed retroperitoneally in the iliac fossa. Ischemia also was not a factor since the mesenteric vessels were patent with no evidence of thrombus formation or vasculitis. The cause appeared to be related to immunosuppressive agents, in particular, high doses of corticosteroids. The disease process appeared to be reversible if immunosuppression was discontinued early, as occurred in two patients.

Adult↗

PubMed1978

Pancreatic cystadenoma. A clinicopathologic study of 45 cases.

Forty-five patients with pancreatic cystadenoma were treated surgically at the Mayo Clinic between 1939 and 1975. Each lesion was classified as mucous or serous. The most frequent lesion site was the tail of the pancreas. The typical patient was a middle-aged woman with upper abdominal pain and a palpable mass on initial examination. Total extirpation of the cystadenoma was the treatment of choice; internal drainage or external drainage of these cysts should not be done. Occasionally, the nearness of the tumors to the mesenteric vessels precluded excision. The mucous type had malignant potential whereas the serous does not. None of the cystadenomas subsequently underwent malignant degeneration. Because of the slow-growing characteristics of the tumor, undue operative risks should not be taken.

Adult↗

PubMed1978

Mesenteric fibromatosis in Gardner's syndrome.

Two patients with mesenteric fibromatosis in Gardner's syndrome were treated by us. These tumors are slow-growing and may remain quiescent for long periods. Review of similar cases in the literature discloses that less than half of these tumors have been removed, pointing to the difficulty of their resection. Dissection of the infraduodenal portion of superior mesenteric vessels may help define whether these tumors are resectable. Radiation therapy or treatment with antiestrogens may be helpful in the treatment of unresectable tumors.

Adult↗

PubMed1981

Balloon-catheter dilation as an adjunct to arterial surgery.

Balloon-catheter dilation of arterial stenoses and/or occlusions has been found to be helpful when used both as an adjunct to arterial surgery and as definitive treatment. Used preoperatively, it enables the extent of surgery to be limited and may improve the patient's general condition and ability to undergo surgery; such is seen when renal or mesenteric vessels are dilated preoperatively. During surgery, it can be used to augment the surgery, particularly in an area that is difficult to expose or out of the operative field. Postoperatively, it is often useful in maintaining patency of a graft or its inflow and outflow tract. Judicious use of this modality can enhance arterial surgery and improve results.

Arterial Occlusive Diseases↗

PubMed1992

How secure are laparoscopically placed clips? An in vitro and in vivo study.

We tested the security of laparoscopic, hemostatic clips in vitro and in vivo. In vitro, the force needed to transversely dislodge clips that were applied to silicone (Silastic) tubing ranged from a mean +/- SEM of 1.81 +/- 0.07 N (Endo Clip) to 2.68 +/- 0.04 N (Ligaclip). The force needed to axially dislodge clips that were applied to silicone tubing ranged from 4.08 +/- 0.20 N (Endo Clip) to 4.78 +/- 0.18 N (Ligaclip). In vivo, on mesenteric vessels in anesthetized pigs, 34 of 100 clips that were applied laparoscopically with the Endo Clip were moved or dislodged compared with 11 of 100 of those applied with the Ligaclip. We conclude that laparoscopically placed vascular clips applied with the Ligaclip are more secure than those applied with the Endo Clip. The laparoscopic surgeon should be aware of the relative ease with which clips may be dislodged.

Animals↗

PubMed1995

The ability of laparoscopic clips to withstand high intraluminal pressure.

OBJECTIVE: To determine if commercially available clips for laparoscopic surgery become displaced with high intraluminal pressures. DESIGN: In vivo model in which the splenic, renal, and mesenteric vessels together with the gallbladder of anesthetized living pigs were individually occluded using titanium and absorbable clips and then subjected to pressures of 300 mm Hg; and in vitro model in which the procedure was repeated on freshly removed human gallbladders with the attached segment of cystic duct. INTERVENTION: The intraluminal pressure of the occluded segment was increased until (1) the clip was released, (2) the vessel burst, or (3) the predetermined pressure (300 mm Hg) was obtained. RESULTS: A total of 90 clips were examined. No clip could be displaced from any porcine vessel at intraluminal pressures of up to 300 mm Hg. One vessel burst before the predetermined pressure was obtained, the clips remaining intact. Clips placed on the porcine and human models also could not be displaced by a pressure of 300 mg Hg. CONCLUSION: Commercially available titanium and absorbable clips do not disrupt when subjected to high intraluminal pressures. Postoperative bile leaks are more likely to result from necrosis of the cystic duct than displacement of the clip by the pressure within the biliary system.

Animals↗

PubMed1999

Preoperative sonographic diagnosis of midgut malrotation with volvulus in adults: the "whirlpool" sign.

Midgut malrotation and volvulus, found mostly in children, are rare and difficult to diagnose preoperatively in adults. We report 2 cases in which a 68-year-old man and a 75-year-old woman presented with intermittent cramping abdominal pain, abdominal distention, and vomiting. Abdominal sonography demonstrated wrapping of the superior mesenteric vein and bowel loops around the superior mesenteric artery (the "whirlpool sign") in both patients. Abdominal CT revealed similar findings. The diagnoses of midgut volvulus and mesenteric malrotation were made, and the patients underwent laparotomy. The man was confirmed to have duodenojejunal malrotation and volvulus, and the woman had cecal volvulus. The whirlpool sign is valuable for the preoperative diagnosis of mesenteric vessel malrotation and midgut volvulus.

Aged↗

PubMed2005

Overexpression of the Del1 gene causes dendritic branching in the mouse mesentery.

In the present study, we established transgenic mice overexpressing Del1, a ligand of integrins, to examine the effect of overexpression of Del1 on vascular morphogenesis. In the wild-type mouse, mesenteric vessels are shaped like rakes consisting of a long stalk and short branches at the periphery. In contrast, those in transgenic mice showed typical dendritic architecture consisting of a few large primary branches with smaller spreading branches. The phenotype of mice overexpressing Del1 suggests the existence of a tissue-specific mechanism for branching morphogenesis in the mesentery.

Animals↗

PubMed1995

Management of alimentary tract duplication in children.

Duplication of the alimentary tract is rare but potentially dangerous. Five of 72 children with alimentary tract duplication treated between 1973 and 1992 died from postoperative complications; a further ten required more than one operation. Ileal duplications were the commonest, occurring in 16 patients (22 per cent). Thoracoabdominal duplications were the most complicated and responsible for much of the overall morbidity and mortality. Surgical complications were related to the size and location of the duplication, communication with the gastrointestinal tract or vertebral canal, presence of heterotopic gastric mucosa and involvement of mesenteric vessels. Complete excision of the duplication should be possible in most cases.

Adolescent↗

PubMed1995

Diagnostic laparoscopy combined with laparoscopic ultrasonography in staging of cancer of the pancreatic head region.

The aim of this study was to assess the additional role of diagnostic laparoscopy combined with laparoscopic ultrasonography in the staging of patients with pancreatic head malignancy. Between January 1993 and June 1994, 73 patients with stage I cancer of the pancreatic head determined by preoperative investigation (endoscopic retrograde cholangiopancreatography and Doppler ultrasonography) were eligible for laparoscopic ultrasonography. The peritoneal cavity was investigated for peritoneal deposits, intrahepatic metastases, malignant infiltration of the portal and superior mesenteric vessels, and N3 lymph node metastases. All patients without histologically proven metastases proceeded to laparotomy. Seventy patients were eligible for evaluation. Sixteen of the 21 patients with distant metastases were diagnosed by laparoscopy with ultrasonography. Forty-nine patients had surgical exploration and trial dissection to assess local resectability. Twenty-nine patients (41 per cent) had resectable pancreatic head tumours. The positive predictive value of local ingrowth as determined by laparoscopic sonography was 93 per cent. Laparotomy was avoided in 19 per cent of patients and the preoperative stage was changed in 41 per cent. Laparoscopy including ultrasonography was effective in staging pancreatic head malignancy.

Humans↗

PubMed2005

Management of midgut carcinoids.

Midgut carcinoids developing in the small intestine represent the most common cause of the carcinoid syndrome, with severe symptoms of flush, diarrhoea, and fibrotic valvular heart disease. The tumours may be histologically identified with specific chromogranin A or synaptophysine immunostainings, and by serotonin reactivity, which supports a midgut origin. Urinary 5-HIAA excretion and serum chromogranin A measurements are used as biochemical tumour markers for clinical diagnosis, and as important monitors of treatment effects and prognostic predictors. The midgut carcinoids have typically slow proliferation and extended disease course, and surgical treatment has become increasingly important for their management. Surgery should aim to remove primary tumours and mesenteric metastases, which may cause long-term abdominal complications, by typical fibrotic intestinal entrapment and small bowel ischaemia due to encasement of mesenteric vessels. Attempts should also be made to surgically remove or ablate liver metastases, since this may significantly contribute to palliation of the carcinoid syndrome. In patients with this syndrome surgery is combined with continuous biotherapy with long-acting somatostatin analogues and interferon, which may alleviate symptoms and cause stable disease with slow progression. Favourable survival and life-quality can be expected with this treatment also in patients with advanced midgut carcinoids.

Balloon Occlusion↗

PubMed1993

Identification of dopamine1A receptors in the rat small intestine.

Dopamine receptors have been localized to several tissues outside the central nervous system including the kidney and mesenteric vessels. To determine if there are dopamine1 receptors within the small intestine, homogenates of the antimesenteric halves of the entire jejunum and ileum of adult rats were prepared and competitive inhibition studies and Scatchard analysis were performed at room temperature using 125I-SCH 23982 and SCH 23390. The specific binding of 125I-SCH 23982 to the intestinal tissue homogenates was rapid, saturable with ligand concentration, and reversible. Analysis of the Scatchard plots revealed a single class of receptors with an apparent dissociation constant of 10.77 +/- 2.32 nM and maximum receptor density of 1.37 +/- 0.34 fmole/mg protein. Emulsion autoradiography performed using 125I-SCH 23982 on antimesenteric sections of the rat small intestine revealed that the dopamine1 receptors are located on cells at the base of the intestinal crypts. Two dopamine1 subtypes (D1A and D1B) have been identified by molecular biological techniques. Using a ribonuclease protection assay we found expression of the D1A receptor gene in the small intestinal tissue. These studies are the first to identify, characterize, and localize receptors for the endogenous catecholamine, dopamine, within the rat small intestine and to confirm the expression of the D1A receptor gene.

Animals↗