Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00530 (Portal)
 4,208 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to determine portal blood flow and mitochondrial and hepatic function during extrahepatic obstruction. Twenty-two male Wistar rats which had undergone bile duct ligation were compared 7 days later to 20 sham-operated controls. Portal flow and mitochondrial respiratory control ratio were reduced by 50% and 35%, respectively (P less than 0.01), and serum alanine-aminotransferase levels increased significantly (P less than 0.01) in the extrahepatic cholestatic group. These results suggest that cholestasis may cause an imbalance between the energy supply and the high demand of the liver leading to a state of partial ischemia.
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PMID:Portal flow and mitochondrial function during extrahepatic cholestasis. 322 50

The elevation of serum alkaline phosphatase (ALP) that develops in the dog after 24 hours of colon ischemia was studied to determine its tissue origin. Portal, hepatic, and aortic blood were sampled but no difference in ALP level among these sites was found. In sera shown to have a significant rise in ALP, other tests of liver function were unchanged from normal, suggesting the ALP did not originate from the liver. On electrophoresis the "ischemic ALP" migrated faster than a known liver ALP standard but more slowly than an intestinal ALP sample.
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PMID:Studies on the alkaline phosphatase rise following colon ischemia. 746 48

Experimental and clinical observations indicate that the liver allograft is less immunogenic than other organ transplants and can promote immune tolerance. Because interleukin-10 recently emerged as a macrophage and T-cell-derived cytokine with potent immunosuppressive properties, we studied its production in 28 patients undergoing orthotopic liver transplantation. Plasma levels of immunoreactive interleukin-10 dramatically increased within 2 hr after liver allograft reperfusion, with peak levels ranging between 214 and 4998 pg/ml (median = 677 pg/ml). This systemic release of interleukin-10 was transient because it returned to low levels by 48 hr (range = 26 to 51 pg/ml). The higher interleukin-10 levels measured in right atrial blood as compared with portal blood indicated that interleukin-10 was most likely synthesized within the liver graft. To get insight into the cellular origin of interleukin-10, we also measured serum levels of interleukin-4 and interferon-gamma, both produced by T cells, and interleukin-8, a cytokine secreted by macrophages, in eight patients. Interleukin-4 and interferon-gamma levels remained undetectable in most of the patients, whereas interleukin-8 levels paralleled those of interleukin-10. Portal endotoxemia was probably not involved in interleukin-10 production because endotoxin levels remained low (< 20 pg/ml) before and after liver allograft reperfusion. Interleukin-10 plasma levels did not correlate either with cold ischemia time or with the occurrence of rejection episodes. We conclude that orthotopic liver transplantation is associated with a massive release of interleukin-10 and interleukin-8, most likely produced by allograft macrophages.
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PMID:Systemic release of interleukin-10 during orthotopic liver transplantation. 792 30

It is possible that the mucosal damage in congestive gastropathy of portal hypertensive patients may have an ischemic basis, since rewarming time in other sites correlates with local blood flow, a method was designed to assess the capacity of the gastric mucosa to rewarm the stomach after a cold challenge, as an index of ischemia. Eleven control subjects and 15 patients with portal hypertension (10 treated with sclerotherapy) were studied with an integrated circuit temperature transducer connected to a digital display. A balloon containing the temperature transducer inside was reversibly fixed 10 cm. proximally to the distal end of a panendoscope. Once upper endoscopy was completed, the balloon placed in the antrum was infused with cooled water (2 degrees C) through a polyethylene tube. The time elapsed for the water to be rewarmed from 20 degrees C to 25 degrees C to 30 degrees C and 20 degrees C to 30 degrees C was measured. Reproducibility of repeated measurements, gave a coefficient of variation of 6%. Total rewarming time was (-mean +/- SD) 178 +/- 51.3 seconds, significantly higher in Portal hypertensive patients as compared to 114 +/- 34.7 seconds in Controls (P < 0.001). (95% Confidence Interval: -X = 63.4 seconds Cl 45.02 to 81.78). 60% of Sensitivity and 100% of Specificity The slower rewarming time in patients with portal hypertension may be the result of mucosal ischaemia, but oedema and cellular infiltration could also affect the heat flow.
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PMID:A new method to assess gastric mucosa rewarming time in patients with portal hypertension. 805 87

The purpose of this experimental study was to determine the hemodynamic conditions of intraperitoneal viscera during pneumoperitoneum by using either CO2 gas or helium (He) for insufflation. In 16 mongrel dogs (divided into a CO2 group and an He group) subjected to 14 mmHg pneumoperitoneum for 60 min, the following parameters were assessed at times before and 1, 2, 5, 15, 30, 45, and 60 min thereafter: (1) intestinal mucosal blood flow, by means of a laser-Doppler probe inplanted into a jejunal loop; (2) portal pressure and portal blood pCO2, through a catheter inserted via a mesenteric jejunal vein; (3) intramural jejunal pH (pHi), by means of a Tonometer, which expresses the degree of tissue ischemia; (4) inferior vena cava pressure and blood pCO2, through a catheter inserted via a femoral vein; and (5) from the systemic circulation pulse rate, arterial blood pressure, CO, CVP, PVP, SaO2, pCO2, and paO2 were measured through a catheter placed into a femoral artery and a Swan-Ganz thermodilution catheter inserted via external jugular vein: CI and SVR were then calculated. Jejunal mucosal blood flow was found decreased (P < 0.0001) and pHi revealed gut mucosal ischemia. Portal and inferior vena cava pressures were found to be elevated (P < 0.0001), as was blood pCO2 of these vessels (P < 0.001), in only the CO2 group. From the systemic circulation, arterial blood pressure, CO, CI, SaO2, and paO2 revealed a decrease (P < 0.001) while arterial pCO2 (only CO2 group), CVP, SVR, and PVP revealed an increase (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic events in the peritoneal environment during pneumoperitoneum in dogs. 827 94

Leukocyte adhesion may play a central role in the pathogenesis of preservation-reperfusion injury to liver grafts. We previously showed that lymphocyte adhesion to sinusoids is dependent on the length of cold ischemia. In the present study we examined the mechanisms of lymphocyte adherence after harvesting combined with a short and a long preservation time. The effects of lymphocyte adherence on liver function were also examined. Rat livers were stored at 1 degrees C in University of Wisconsin solution for 45 min or 30 hr and then reperfused at 37 degrees C in the isolated perfused rat liver with isogeneic lymphocytes in an asanguineous perfusate. The role of reactive oxygen intermediates was investigated with allopurinol, a vitamin E analog and ascorbate or superoxide dismutase and catalase. For us to determine the role of Kupffer cells, Kupffer cell blockade was produced by gadolinium chloride. Leukotriene B4 effects were examined with the lipooxygenase inhibitor, nordihydroguaiaretic acid. We evaluated the possible presence of mechanical obstruction by studying flow rates and the circulation of red blood cells. We examined the role of adhesion molecules by pretreating lymphocytes with trypsin or neuraminidase and by exposing livers to arabinogalactan. We investigated the effects of lymphocyte adhesion on liver function by comparing perfusate liver enzymes in livers reperfused with and without lymphocytes, with trypsinized lymphocytes and with an increased number of lymphocytes. Allopurinol significantly reduced hypoxanthine degradation, and nordihydroguaiaretic acid inhibited leukotriene B4 release into the perfusate. The ability of gadolinium chloride to inhibit Kupffer cells was shown by colloid carbon uptake. In livers harvested and preserved for 45 min, lymphocytes decreased about 40% during reperfusion. In livers preserved for 30 hr, the reduction was significantly greater (about 80%). Lymphocyte adherence was lessened in livers preserved for 45 min by all three of the reactive oxygen intermediate protectants and by gadolinium chloride. In contrast, neither reactive oxygen intermediate protectants nor gadolinium chloride reduced adherence in livers preserved for 30 hr. Nordihydroguaiaretic acid had no effect in livers preserved for either 45 min or 30 hr. Portal flow in livers preserved for 45 min and 30 hr was similar, suggesting an absence of mechanical obstruction, and this finding was supported by a complete absence of red cell trapping. Trypsinization of lymphocytes and exposure of livers to arabinogalactan significantly lessened lymphocyte adherence in livers preserved for 30 hr but not in those preserved for 45 min.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lymphocyte adherence in the reperfused rat liver: mechanisms and effects. 838 Jul 89

Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes (PMN) may play a critical role in ischemia-reperfusion injury. To evaluate whether similar mechanisms are operative in human liver, six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were randomized for utilization of hepatic vascular exclusion (HVE) as a model of ischemia-reperfusion injury. Portal and systemic levels of acute reactant cytokines (interleukin 6 [IL-6], interleukin 1 [IL-1], tumor necrosis factor alpha [TNF-alpha]) and neutrophil adhesion in serial liver biopsy specimens were studied. Correlations among mediators, leukocyte adhesion, and markers of liver injury were also evaluated. Hepatic vascular exclusion resulted in substantial and reproducible changes in portal and arterial IL-6 levels in both cirrhotic and noncirrhotic patients. Portal and systemic cytokine levels were comparable in most instances, whereas levels were usually higher in cirrhotic patients than in noncirrhotic patients. Negative correlations were found between IL-6 levels at the time of reperfusion and later TNF-alpha levels. IL-6 levels correlated negatively with numerous markers of hepatocellular injury and the number of postoperative complications. Hepatic vascular exclusion increased neutrophils adhesion after reperfusion in cirrhotic patients but not in noncirrhotic patients. In cirrhotic patients, the degree of leukocyte adhesion after reperfusion correlated with several postoperative markers of liver injury. This study in humans shows that acute reactant cytokines are released during liver ischemia and, interestingly, that IL-6 levels strongly correlate with clinical and laboratory measures of injury. Further studies to evaluate possible causal relationship with hepatic injury are warranted, with emphasis on the role of IL-6 and PMN adhesion.
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PMID:Acute reactant cytokines and neutrophil adhesion after warm ischemia in cirrhotic and noncirrhotic human livers. 867 64

An in vivo rat model of isolated intestinal ischemia-perfusion was developed. This is used to compare the effects of crosslinked hemoglobin (PolyHb) versus crosslinked hemolobin-superoxide dismutase-catalase (PolyHb-SOD-CAT) on free radical generation in ischemia-reperfusion. Fasted, anesthetized male Sprague Dawley rats underwent midline laparotomy with cannulation of the abdominal aorta and inferior vena cava. Ligation was carried out at the renal pedicles bilaterally and the aorta and vena cava proximally at the diaphragm and distally above the femoral bifurcation. The system was flushed of blood with 20 ml of lactated Ringer's solution. The portal vein was then cannulated with distal clamping at the porta hepatis so that isolated intestinal perfusion could be achieved with the aorta as the inlet and the portal vein as the outlet. Following a 90 minute ischemic time, perfusates containing modified hemoglobin (5 g/dl) and 4-hydroxybenzoate (5 mM) were infused at 0.8 ml/min for 10 min. Portal vein effluent samples were collected at 2.5 minute intervals. Hydroxyl radical generation was assessed by an aromatic hydroxylation technique with 4-hydroxybenzoate (4HB). Reaction of hydroxyl radical with 4HB produces 3,4 dihydroxybenzoate (3,4 DHBA). In the PolyHb group, the levels of 3,4-DHBA increased 10.75-13.58 x-fold above pre-perfusion values compared to 2.25-3.75 x-fold in PolyHb-SOD-CAT group. This indicates that PolyHb-SOD-CAT is effective in reducing in vivo hydroxyl radical generation following reperfusion. Since free radicals may play a major role in the pathogenesis of ischemia-reperfusion injury, this suggests a role for PolyHb-SOD-CAT as a possible protective perfusate in intestinal reperfusion injury.
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PMID:Crosslinked hemoglobin-superoxide dismutase-catalase scavenges free radicals in a rat model of intestinal ischemia-reperfusion injury. 908 38

The authors investigated whether amelioration of intestinal mucosal injury, due to ischemia-reperfusion (I/R), with oxygenated perfluorocarbon (PFC) would reduce an oxidant-generated lung injury. The small intestine is increasingly recognized as a primary effector of distant organ injury. Clinical and experimental studies suggest oxidant species and activated neutrophils as the agents responsible for lung injury after intestinal I/R. The role of intestinal mucosal injury has not been defined. Oxygenated PFC was perfused through the lumen of the intestine during periods of I/R. Portal venous effluent was examined for reactive oxygen species and lung tissue was examined for lipid peroxidation. Luminal perfusion of oxygenated PFC during intestinal I/R reduced oxidant species in the portal blood. This correlated with a reduction in lung lipid peroxidation. Oxygenated PFC prevented intestinal mucosal injury resulting from induced I/R. Amelioration of mucosal injury reduced oxidant generation in the portal venous circulation that was proportional to the reduction in measured lung injury. Protection of the mucosa with intraluminal oxygen may prevent I/R-associated lung injury.
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PMID:Mucosal protection from intestinal ischemia-reperfusion reduces oxidant injury to the lung. 944 91

Intestinal ischemia may evoke an inflammatory response and eventually multiple organ failure. We investigated whether intestinal ischemic injury induces systemic lipid peroxidation and changes in the plasma antioxidant capacity in a pig model. Together with cardiovascular parameters, arterial and portal venous blood of 7 pigs were measured for thiobarbituric acid-reactive material diene conjugates, fluorescent chromolipids and plasma antioxidant capacity during graded occlusion of superior mesenteric artery and reperfusion. Plasma levels of lipid peroxidation products did not change significantly during graded ischemia and reperfusion. Portal venous plasma antioxidant capacity increased slightly during reperfusion (from 96.16 +/- to 3.91 to 142.49 +/- 12.01 mumol/l, p < 0.05). Although elevated levels of free radical reaction products have been found in ischemia-reperfusion, we found no evidence of systemic lipid peroxidation in our intestinal ischemia model.
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PMID:Lipid peroxidation products and antioxidant capacity in portal venous and systemic arterial plasma during gradual intestinal ischemia and reperfusion in pigs. 956 42


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