Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most modifications and applications of the orthotopic rat liver transplantation (ORLT) model require clamping of the portal vein, thus leading to ischemia of the gut. The purpose of this study was to evaluate the effect of portal vein clamping during ORLT on hepatic microcirculation and leukocyte--endothelial interaction by intravital fluorescence microscopy. ORLT were performed following 1 hr of cold storage in EuroCollins solution without (standard group) and with insertion of a portojugular shunt (shunt group) to minimize intestinal ischemia. ORLT induced reduction of perfused sinusoids (83%) and velocity of leukocytes (311 +/- 4.5 microns/sec; mean +/- SEM) compared with nontransplanted controls (99% and 417 +/- 4.9 microns/sec). Portojugular shunt during ORLT improved hepatic microvascular perfusion (89% and 355 +/- 3.4 microns/sec; P less than 0.05). Furthermore, percentage of permanent and temporary adherent leukocytes decreased significantly when a portosystemic shunt was applied (from 33.5 +/- 1% to 22.1 +/- 1% and 19.7 +/- 1.2% to 14.0 +/- 0.9%; P less than 0.05). The results of the study reveal that intestinal congestion and reperfusion results in a rise in leukocyte adhesion to the sinusoidal wall and in disturbances of the hepatic microcirculation. It seems likely that increased endotoxin concentrations in the portal vein induce an activation of hepatic macrophages that subsequently cause release of chemoattractant mediators. In conclusion, side effects of intestinal ischemia during experimental liver transplantation surgery on liver function due to release of chemoattractant mediators should be considered when experimental data are transferred to clinical settings.
 ...
PMID:Hepatic microcirculatory disturbances due to portal vein clamping in the orthotopic rat liver transplantation model. 189 13

Infusing pigs with lipopolysaccharide (LPS) decreases superior mesenteric artery blood flow (Qsma), suggesting that mesenteric hypoperfusion may be responsible for LPS-induced alterations in gut mucosal permeability. To test this hypothesis, we studied four groups of anesthetized swine. Group 1 animals (N = 6) were infused with LPS (250 micrograms/kg over 1 hour beginning at 60 minutes) and continuously resuscitated with Ringer's lactate (48 mL/kg per hour). In group 2 (N = 5), Qsma was decreased by 50% by means of a mechanical occluder to mimic the LPS-induced alterations in Qsma observed in group I. Group 3 (N = 5) was included to document our ability to detect ischemia/reperfusion-induced alterations in mucosal permeability; in these pigs, Qsma was decreased in steps to zero flow (at 150 to 210 minutes) and then perfusion was restored (at 210 to 270 minutes). Pigs in group 4 (N = 6) served as normal controls; these animals were resuscitated with Ringer's lactate at the same rate as in group 1 but were not infused with LPS. To assess mucosal permeability, we measured plasma-to-lumen clearances for two markers, chromium 51-labeled edetic acid monohydrate (EDTA) and urea. Loading and maintenance infusions of the markers were given intravenously, and a 20-cm isolated segment of small intestine was continuously perfused at 2 mL/min with Ringer's lactate at 37 degrees C. Results were expressed as the ratio of the clearances for the two probes (CEDTA/CUREA). In group 3, CEDTA/CUREA was 999% +/- 355% of baseline at 270 minutes. In group 1, CEDTA/CUREA was 572% +/- 235% of baseline at 270 minutes. In groups 2 and 4, however, CEDTA/CUREA did not change significantly from the baseline value over the duration of the study. These data suggest that increased mucosal permeability after LPS is due to factors other than (or in addition to) mesenteric hypoperfusion.
 ...
PMID:Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor. 189 58

Mechanical ventilation with positive end-expiratory pressure (PEEP) diminishes gut and hepatic blood flow and redistributes cardiac output away from the splanchnic circulation. This flow-limited environment can aggravate underlying hypoperfusion and ischemia in the postinjury setting. To examine the effects of low dose dopamine on a lung injury PEEP model of gut hypoperfusion, six anesthetized, splenectomized canines were instrumented with arterial, pulmonary artery, portal vein, and hepatic vein catheters. Electromagnetic flow probes were placed around the hepatic artery and portal vein for continuous flow measurements. Gut and hepatic blood flow, oxygen delivery, oxygen consumption, and extraction ratio were calculated at four time points: baseline, 1 hr after lung injury with oleic acid, 1 hr after ventilation with 10 cm H2O PEEP, and 1 hr after the continuous infusion of dopamine. Portal flow and gut oxygen delivery fell significantly with the infusion of PEEP. These values returned to near baseline levels with the addition of dopamine. Gut oxygen extraction increased from 16 +/- 2% to 35 +/- 3% with PEEP but returned to near baseline with dopamine (20 +/- 4%, P less than 0.01 compared to PEEP). We conclude that dopamine improves blood flow and oxygen delivery to the gut in this flow-limited model. This may preserve splanchnic physiology during PEEP ventilation for acute lung injury.
 ...
PMID:The effect of low dose dopamine on gut hemodynamics during PEEP ventilation for acute lung injury. 190 74

Gut barrier failure and bacterial translocation (BT) after thermal injury may result from splanchnic vasoconstriction and intestinal ischemia. The role of the renin-angiotensin system in intestinal blood flow and BT after thermal injury was studied by pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril in Wistar rats before sham or 30% scald burn. Adequacy of ACE inhibition was documented by the absence of a hypertensive response to angiotensin I, and intestinal blood flow was determined using 51Cr-labeled microspheres. Small bowel blood flow was decreased by 46% at 4-h postburn (P less than 0.05) in untreated burned animals despite maintenance of normal cardiac index but returned to baseline levels by 24 h after injury. Enalapril pretreatment resulted in maintenance of small bowel blood flow after thermal injury and was associated with a significantly reduced incidence of BT (20% vs. 75% in untreated burned animals, P less than 0.01). These findings further implicate intestinal ischemia in the etiology of gut barrier dysfunction after thermal injury, mediated in part by activation of the renin-angiotensin system.
 ...
PMID:Splanchnic vasoconstriction and bacterial translocation after thermal injury. 192 2

Hela S3 cells were grown in suspension both randomly and, synchronously using hydroxyurea which blocks cells at the G1/S interface. Cryosections were prepared, freeze-dried and analyzed by X-ray microanalysis. As cells moved into S and through M phases [Na] and [Cl] increased; both returned to normal levels upon re-entering G1 phase. The Na/K ratio was 1:1 in G1 phase. Infection of HeLa S3 cells in G1 phase with vaccinia virus resulted in no change in intracellular [Na]. Infection of neonatal mice with murine rotavirus was localized to villus tip enterocytes and gave rise to diarrhoea which was maximal at 72h post-infection (p.i.). Diarrhoea was preceded by ischemia of villi (18-42h p.i.) and villus shortening (maximal at 42h p.i.), and was also coincident with a dramatic regrowth of villi. At 48h p.i. a proliferative zone of electron lucent cells was observed in villus base regions. Cryosections of infected gut, taken before, during, and after infection, together with corresponding age-matched controls, were freeze-dried and analysed by X-ray microanalysis. At 48h p.i. electron lucent villus base cells were shown to be more hydrated, and, to contain higher levels of both Na and Cl and lower levels of P, S, K and Mg than corresponding control cells. These studies (we argue) increase confidence in the use of X-ray microanalysis in studying biological systems, provide some insight into the process of cell division, and constitute the basis of a new concept of diarrhoeal secretion.
 ...
PMID:From HeLa cell division to infectious diarrhoea. 196 48

Bacterial translocation (BT) occurs transiently after thermal injury and may result from an ischemic intestinal insult. To evaluate continued intestinal ischemia in the ongoing BT associated with sepsis after injury, rats were randomized to (1) 30% burn injury with Pseudomonas wound infection (BI), (2) BI + fluid resuscitation (BI + Fluid), (3) BI after allopurinol pretreatment to inhibit xanthine oxidase (BI + Allo), or (4) BI after azapropazone pretreatment to inhibit neutrophil degranulation (BI + Aza). On postburn days (PBD) 1, 4, and 7, animals were studied for evidence of BT and intestinal lipid peroxidation. BI + Fluid, BI + Allo, and BI + Aza significantly (p less than 0.05) reduced rates of BT and ileal lipid peroxidation acutely after thermal injury (PBD 1) compared to BI. All four groups had equally high rates of BT associated with the onset of sepsis (PBDs 4 and 7), without evidence of further intestinal lipid peroxidation. These data indicate that the chronic gut barrier failure associated with sepsis after injury occurs independently of continued intestinal ischemia.
 ...
PMID:Differential pathophysiology of bacterial translocation after thermal injury and sepsis. 206 68

Transient episodes of gut mucosal ischemia occur in many patients having cardiac surgery. Ischemic mucosal injury increases mucosal permeability and promotes the translocation of bacterial toxins and bacteria and, hence, the release of mediators. Collectively these substances are the putative cause of LOS, nosocomial infections, and MSOF. Circumstantial evidence suggests that the morbidity and mortality from cardiac surgery might be greatly reduced by preventing or limiting in duration the episodes of gut mucosal ischemia. This objective is unlikely to be reliably achieved in clinical practice without monitoring the adequacy of gut mucosal oxygenation. The adequacy of gut mucosal oxygenation can be conveniently monitored in the stomach with a Tonomitor incorporated into a nasogastric tube, because changes induced in this organ by disturbances in DO2 reflect changes occurring in other parts of the gut. Preventative measures currently possible in routine clinical practice include maintaining an intramucosal pH at normal levels by optimizing DO2, preventing the release of splanchnic vasoconstrictors and the formation of cellular aggregates by the use of pulsatile perfusion during bypass, and minimizing oxygen requirements with cooling and muscle relaxation. The translocation of bacterial toxins and bacteria across injured mucosa may be minimized by gut lavage before surgery. Therapeutic measures for gut mucosal ischemia currently possible in routine clinical practice include, in addition to the preventative measures outlined above, the prevention of free radical-induced mucosal injury during resuscitation, parenteral antibiotics, the treatment of sepsis, and the resection of infarcted gut.
 ...
PMID:Gut mucosal ischemia during cardiac surgery. 209 99

Celiac compression is usually a benign condition, but when surgery necessitates division of collaterals from the superior mesenteric artery, it may cause life-threatening gut ischemia. We report a case of cholangiocarcinoma necessitating pancreaticoduodenectomy in a patient with celiac artery compression by the median arcuate ligament. Preoperative duplex scanning confirmed the celiac stenosis and revealed retrograde flow through collaterals from the superior mesenteric artery. Intraoperative continuous wave Doppler examination revealed that gastric blood flow disappeared with compression of the superior mesenteric artery. This maneuver no longer affected gastric flow after transection of the compressing structures at the celiac origin. Preoperative identification of celiac artery stenosis is crucial to prevent small bowel ischemia and possible anastomotic breakdown or liver failure. Duplex scanning can provide important insight about collateral circulation, and intraoperative Doppler testing can assess the adequacy of revascularization.
 ...
PMID:Pancreaticoduodenectomy and the celiac artery compression syndrome. 215 92

Several studies have demonstrated that granulocytes accumulate in the intestinal mucosa following ischemia/reperfusion. It has been suggested that leukotriene B4 may be released during ischemia/reperfusion and consequently may promote granulocyte infiltration into the mucosa. The objectives of this study were to determine whether (a) leukotriene B4 is produced in the gut mucosa during ischemia and reperfusion, and (b) inhibition of leukotriene B4 attenuates granulocyte infiltration into the postischemic intestinal mucosa. Isolated segments of cat intestine were subjected to 3 hours of ischemia and 1 hour of reperfusion. Mucosal samples were obtained during baseline, ischemia at 3 hours and reperfusion at 1 hour. Leukotriene B4 production was determined by radioimmunoassay. Tissue-associated myeloperoxidase activity was used to quantitate granulocyte accumulation in the mucosal samples. In untreated animals, mucosal leukotriene B4 concentration was higher at reperfusion compared with baseline levels. The reperfusion-induced increase in mucosal leukotriene B4 was entirely prevented by pretreatment with either nordihydroguaiaretic acid (Sigma Chemical Co., St. Louis, MO) or L663,536 (Merck-Frosst, Montreal, Quebec, Canada), two potent lipoxygenase inhibitors. Both lipoxygenase inhibitors, as well as leukotriene B4 antagonist (SC-41930) significantly attenuated the reperfusion-induced infiltration of granulocytes. These results indicate that leukotriene B4 plays an important role in mediating the granulocyte accumulation elicited by reperfusion of the ischemic bowel.
 ...
PMID:Role of leukotriene B4 in granulocyte infiltration into the postischemic feline intestine. 217 Feb 22

Acute lung injury characterized by increased microvascular permeability is one feature of multiple-organ system failure and the adult respiratory distress syndrome. Intestinal ischemia-reperfusion injury has been linked to this type of acute lung injury. The purpose of these experiments was to examine the pathogenic mediators that link the two processes, with particular emphasis on the roles of endotoxin and tumor necrosis factor alpha (TNF alpha). Previously described characteristics of the acute lung injury in this rat model of intestinal ischemia-reperfusion include pulmonary neutrophil sequestration, depletion of lung tissue ATP, alveolar endothelial cell disruption, and increased microvascular permeability. Plasma levels of TNF in the systemic circulation of sham-operated animals and those with intestinal ischemic injury less than 60 minutes in duration were very low or undetectable. Intestinal ischemia for 120 minutes was associated with TNF elevation to 1.19 +/- 0.50 U/mL. Reperfusion for periods of 15 and 30 minutes generated 5- to 10-fold increases in circulating TNF levels (6.61 +/- 3.11 U/mL, p greater than 0.05 and 10.41 +/- 5.41 U/mL, p = 0.004 compared to sham); however this increase in circulating TNF was transient and largely cleared within 60 minutes after initiating reperfusion. Portal vein endotoxin levels were found to increase significantly before the appearance of TNF in systemic plasma, suggesting that gut-derived endotoxin may induce TNF release from hepatic macrophages into the systemic circulation. Anti-TNF antibody attenuated the increase in pulmonary microvascular permeability in this preparation but did not prevent pulmonary neutrophil sequestration. These observations suggest that endotoxin and TNF have pathogenic roles in this acute lung injury, but that mechanisms of adherence of neutrophils to endothelial cells independent of TNF may be involved. The accumulation of neutrophils in the lung but the prevention of a vascular permeability increase in the presence of antibody to TNF may imply an in vivo role for TNF in the process of neutrophil activation. These studies provide additional evidence of the importance of the endogenous inflammatory mediators in the development of systemic injury in response to local tissue injury.
 ...
PMID:Evidence for tumor necrosis factor-induced pulmonary microvascular injury after intestinal ischemia-reperfusion injury. 217 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>