Acute mesenteric ischemia.

Acute mesenteric ischemia is a life-threatening surgical emergency associated with high morbidity and mortality rates. Presentation, physical exam, laboratory values and non-invasive imaging may all be non-specific. Angiography remains the gold standard for diagnosis. Advanced age and delay in diagnosis are associated with increased morbidity and mortality rates. Treatment includes resuscitation, mesenteric revascularization and resection of necrotic bowel. Multiple options exist for revascularization and include both open and endovascular approaches.

Hemodynamic conditions at the carotid bifurcation during protective common carotid occlusion.

OBJECTIVES: Carotid angioplasty and stenting procedures are associated with an obligatory release of particulate debris into the distal cerebral circulation. Although most of the emboli are small and do not result in symptomatic neurologic deficits, some may be large enough to cause stroke. For this reason, a variety of filters and balloon occlusion devices have been employed as adjuvants to decrease the risk of distal embolization during carotid stenting. Some of these devices rely on the arrest of antegrade blood flow with the use of inflow arrest. The present study was undertaken to investigate the hemodynamic conditions that exist at the carotid bifurcation during common carotid artery (CCA) occlusion. METHODS: Internal carotid artery (ICA) and external carotid artery (ECA) stump pressures were measured in 29 patients undergoing carotid endarterectomy. Duplex ultrasound scanning was used to measure the direction and velocity of blood flow in the ICA and ECA with the CCA cross-clamped but the ICA and ECA open, a clinical scenario analogous to CCA balloon occlusion at the time of carotid angioplasty and stenting. The direction and magnitude of ICA and ECA flow were compared with the stump pressures to determine whether a correlation existed between these variables. RESULTS: The mean stump pressure in the ICA and ECA averaged 56 +/- 16 and 53 +/- 12 mm Hg, respectively. The ICA systolic stump pressure was lower than the ECA systolic stump pressure in six patients (21%), and all of these patients had persistent antegrade systolic duplex blood flow by duplex interrogation during CCA occlusion. The ICA systolic stump pressure exceeded the ECA systolic stump pressure in 19 patients (66%), and all of these patients had retrograde ICA flow during systole. Diastolic flow was also well correlated with the magnitude of the ICA/ECA stump pressure differential, with antegrade diastolic ICA blood flow in all nine patients with an ICA diastolic stump pressure less than the ECA diastolic stump pressure. None of the 10 patients with ICA diastolic stump pressure greater than ICA diastolic stump pressure maintained antegrade ICA diastolic flow, but four of these patients had flow to zero in diastole. Overall, 13 of 29 patients (45%) could be surmised to be at risk for distal embolization to the brain based on the persistence of some element of either systolic or diastolic antegrade ICA flow during common carotid occlusion. CONCLUSIONS: Common carotid occlusion alone appears insufficient to protect against distal embolization during manipulations of the carotid bifurcation. Persistent systolic or diastolic antegrade blood flow occurs in a high proportion of patients, lending credence to the use of additional protective strategies to ameliorate the risk of embolic complications.

External-beam radiation therapy for improved dialysis access patency: feasibility and early safety.

Rectenwald, J. E., Pretus, H. A., Seeger, J. M., Huber, T. S., Mendenhall, N. P., Zlotecki, R. A., Palta, J. R., Li, Z. F., Hook, S. Y., Sarac, T. P., Welborn, M. B., Klingman, N. V., Abouhamze, Z. S. and Ozaki, C. K. External-Beam Radiation Therapy for Improved Dialysis Access Patency: Feasibility and Early Safety. Radiat. Res. 156, 53-60 (2001).Prosthetic dialysis access grafts fail secondary to neointimal hyperplasia at the venous anastomosis. We hypothesized that postoperative single-fraction external-beam radiation therapy to the venous anastomosis of hemodialysis grafts can be used safely in an effort to improve access patency. Dogs (n = 8) underwent placement of expanded polytetrafluoroethylene grafts from the right carotid artery to the left jugular vein. Five dogs received single-fraction external-beam photon irradiation (8 Gy) to the venous anastomosis after surgery. Controls were not irradiated. Shunt angiograms were completed 3 and 6 months postoperatively. Anastomoses, mid-graft, and the surrounding tissues were analyzed. Immunohistochemistry for smooth muscle cell alpha-actin, proliferating cellular nuclear antigen (PCNA), and apoptosis was performed. Incisions healed well, though all animals developed wound seromas. One control suffered graft thrombosis 4 months postoperatively. Angiography/histology confirmed severe neointimal hyperplasia at the venous anastomosis. The remaining seven dogs developed similar amounts of neointimal hyperplasia. PCNA studies showed no accelerated fibroproliferative response at irradiated anastomoses compared to controls. Skin incisions and soft tissues over irradiated anastomoses revealed no radiation-induced changes or increase in apoptosis. Thus we conclude that postoperative single-fraction external-beam irradiation of the venous anastomosis of a prosthetic arteriovenous graft that mimics the situation in humans is feasible and safe with regard to early wound healing.

Preprocedural risk stratification: identifying an appropriate population for carotid stenting.

PURPOSE: Given the uncertainties associated with carotid angioplasty and stenting, the initial assessment of the procedure may be best undertaken in a subgroup of patients at increased risk for complications with standard carotid surgery. In an effort to characterize such a subgroup, we reviewed the results of carotid endarterectomy in patients with and without significant medical comorbidity. METHODS: During a 10-year period 3061 carotid endarterectomies were performed at a single institution and entered prospectively into a registry. A high-risk patient subgroup was identified, defined by the presence of severe coronary artery disease, chronic obstructive lung disease, or renal insufficiency. The outcome of carotid endarterectomy was assessed with respect to perioperative stroke, myocardial infarction, or death, as well as the combined end point of one or more of the end points. RESULTS: The rate of the composite end point stroke/myocardial infarction/death was 3.8% in the total group of 3061 patients who underwent endarterectomy. As individual end points, the rate of stroke was 2.1%, myocardial infarction 1.2%, and death 1.1%. Among the high-risk subset, the composite end point stroke/myocardial infarction/death occurred in 7.4%. This rate was significantly greater than the corresponding rate of 2.9% in the low-risk subset (P <.0005). Similarly, the rate of stroke (3.5% vs 1.7%, P =.008) or death (4.4% vs 0.3%, P <.001) as solitary events was significantly greater in high-risk patients. CONCLUSIONS: Although carotid endarterectomy is an extremely safe procedure in most patients, results are not as favorable in a high-risk subset with severe coronary, pulmonary, or renal disease. The initial clinical evaluation of carotid stenting might best be undertaken in such a high-risk population, one that comprises patients for whom standard therapy is associated with a high rate of complications.

Laparotomy prevents lethal endotoxemia in a murine sequential insult model by an IL-10-dependent mechanism.

Multiple organ dysfunction and death are common sequelae after mesenteric ischemia-reperfusion injury as seen with mesenteric revascularization and thoracoabdominal aortic aneurysm repair. A second insult such as bacterial pneumonia occurring subsequent to the ischemia-reperfusion injury may contribute to these untoward effects. We hypothesized the sequential visceral/lower torso ischemia-reperfusion and endotoxemia in a murine model would increase the magnitude of the proinflammatory cytokine response and decrease survival. C57BL/6 mice underwent 20 min of supraceliac occlusion (IR), sham laparotomy (LAP), or no initial insult (CTRL) followed by intraperitoneal injection of a lethal dose of endotoxin (LPS [lipopolysaccharide 50 mg/kg] or saline vehicle at 24 h. Serum cytokine levels were measured by enzyme-linked immunosorbent assay (IL-10, IL-6) or WEHI bioassay [tumor necrosis factor (TNF)], and survival was determined at 5 days. The role of IL-10 on the TNF response and survival was examined in a subset of mice given mouse anti IL-10 IgM (25 mg/kg intraperitoneally) 2 h prior to the initial insult. Survival after LPS was significantly different (P < 0.05) among the treatment groups (IR, 64%; LAP, 55%; CTRL, 11%) and appeared to trend directly with the magnitude of the initial operation. The serum IL-10 levels in the IR and LAP groups were significantly increased 4 h after the initial insult and remained elevated at 24 h. Peak serum TNF levels after LPS were significantly lower in the IR and LAP groups. Administration of anti IL-10 IgM resulted in uniform mortality and a significant increase in the peak TNF levels after LPS administration for all initial treatment groups. Endogenous production of IL-10 following laparotomy down-regulates the TNF response and improves survival after endotoxemia.

Warfarin improves the outcome of infrainguinal vein bypass grafting at high risk for failure.

OBJECTIVE: Patients with marginal venous conduit, poor arterial runoff, and prior failed bypass grafts are at high risk for infrainguinal graft occlusion and limb loss. We sought to evaluate the effects of anticoagulation therapy after autogenous vein infrainguinal revascularization on duration of patency, limb salvage rates, and complication rates in this subset of patients. METHODS: This randomized prospective trial was performed in a university tertiary care hospital and in a Veterans Affairs Hospital. Fifty-six patients who were at high risk for graft failure were randomized to receive aspirin (24 patients, 27 bypass grafts) or aspirin and warfarin (WAR; 32 patients, 37 bypass grafts). All patients received 325 mg of aspirin each day, and the patients who were randomized to warfarin underwent anticoagulation therapy with heparin immediately after surgery and then were started on warfarin therapy to maintain an international normalized ratio between 2 and 3. Perioperative blood transfusions and complications were compared with the Student t test or with the chi2 test. Graft patency rates, limb salvage rates, and survival rates were compared with the Kaplan-Meier method and the log-rank test. RESULTS: Sixty-one of the 64 bypass grafts were performed for rest pain or tissue loss, and 3 were performed for short-distance claudication. There were no differences between the groups in ages, indications, bypass graft types, risk classifications (ie, conduit, runoff, or graft failure), or comorbid conditions (except diabetes mellitus). The cumulative 5-year survival rate was similar between the groups. The incidence rate of postoperative hematoma (32% vs 3.7%; P = .004) was greater in the WAR group, but no differences were seen between the WAR group and the aspirin group in the number of packed red blood cells transfused, in the incidence rate of overall nonhemorrhagic wound complications, or in the overall complication rate (62% vs 52%). The immediate postoperative primary graft patency rates (97.3% vs 85.2%) and limb salvage rates (100% vs 88.9%) were higher in the WAR group as compared with the aspirin group. Furthermore, the cumulative 3-year primary, primary assisted, and secondary patency rates were significantly greater in the WAR group versus the aspirin group (74% vs 51%, P = .04; 77% vs 56%, P = .05; 81% vs 56%, P = .02) and cumulative limb salvage rates were higher in the WAR group (81% vs 31%, P = .01). CONCLUSIONS: Perioperative anticoagulation therapy with heparin increases the incidence rate of wound hematomas, but long-term anticoagulation therapy with warfarin improves the patency rate of autogenous vein infrainguinal bypass grafts and the limb salvage rate for patients at high risk for graft failure.

Octreotide diminishes luminal nutrient transport activity, which is reversed by epidermal growth factor.

BACKGROUND: Octreotide (SMS) is a somatostatin analogue utilized in patients with short bowel syndrome (SBS) to decrease output. It may inhibit small bowel adaptation by blocking the secretion of trophic hormones such as epidermal growth factor (EGF). This study delineates the effects of SMS and EGF on nutrient transport in SBS. METHODS: One week after 70% jejunoileal resection, 20 New Zealand White rabbits (2 kg) received subcutaneous infusions of saline or EGF (1.5 micrograms/kg/hr) and injections of saline or SMS s.q.b.i.d. The study groups were EGF/saline, saline/saline, saline/SMS, and EGF/SMS. After 7 days of infusion, intestinal brush border membrane vesicles were prepared and nutrient transport measured. RESULTS: SMS reduced active nutrient transport. Kinetics confirmed this was secondary to a reduction in functional carriers in the brush border membrane, without a change in carrier affinity. The coinfusion of EGF ameliorated this effect. On an individual basis, EGF alone did not significantly increase nutrient transport, but when taken as a group, nutrients transport was upregulated 26%. CONCLUSIONS: SMS is detrimental to small bowel adaptation. EGF reverses this effect and may benefit patients with SBS who require SMS to control high intestinal output.

Sequential alterations in gut mucosal amino acid and glucose transport after 70% small bowel resection.

BACKGROUND: Studies in animals with short bowel syndrome (SBS) suggest that up-regulation of nutrient transporter activity occurs as an adaptive response to the loss of absorptive area. It is unclear, however, whether nutrient transport is altered at the cell membrane in SBS. The purpose of this study is to clarify amino acid and glucose transport in small intestinal luminal mucosa after 70% small bowel resection in rabbits. METHODS: New Zealand white rabbits underwent 70% jejunoileal resection (n = 27) or a sham operation (n = 19). Brush border membrane vesicles were prepared from small intestinal mucosa at 1 week, 1 month, and 3 months by magnesium aggregation-differential centrifugation. Transport of L-glutamine, L-alanine, L-leucine, L-arginine, and D-glucose was assayed by a rapid mixing-filtration technique. RESULTS: We observed no difference in uptake of all amino acids and glucose at 1 week. The uptake of amino acids and glucose was decreased by 20% to 80% in animals with SBS at 1 month. By 3 months all uptake values except that of glucose returned to normal. Kinetic studies of the system B transporter for glutamine indicate that the decrease in uptake at 1 month was caused by a reduction in the Vmax (1575 +/- 146 versus 2366 +/- 235, p < 0.05) consistent with a decrease in the number of functional carriers on the brush border membrane. CONCLUSIONS: In addition to the anatomic loss of absorptive area after massive bowel resection, alterations in enterocyte transport function may be responsible for malabsorption in patients with SBS.

The effects of low-dose radiation on neointimal hyperplasia.

PURPOSE: We sought to determine whether low-dose radiation can inhibit neointimal hyperplasia immediately after balloon injury to the common carotid artery and to assess the extent of endothelial regeneration after treatment. METHODS: Sprague-Dawley rats were subjected to balloon injury to the common carotid artery. Immediately after injury rats were treated with a single dose of iridium 192 radiation at 5 gy, 10 gy, and 15 gy or received no radiation (control). Three weeks after injury and treatment, vessels were harvested and compartment areas were measured on fixed specimens. Scanning and transmission electron microscopy, along with Evans blue dye uptake into injured vessels, was used to assess the effect radiation had on endothelial regeneration. RESULTS: Rats receiving radiation at all three doses demonstrated no intimal thickening when compared with rats that were not treated (at 5 Gy 0.01 +/- 0.01 mm2; at 10 Gy 0.02 +/- 0.01 mm2; at 15 Gy 0.05 +/- 0.02 mm2; with balloon injury/no radiation 0.12 +/- 0.02 mm2; p < 0.01). In addition, the groups that were irradiated had no medial thickening when compared with control rats (at 5 Gy 0.22 +/- 0.02 mm2; at 10 Gy 0.21 +/- 0.02 mm2; at 15 Gy 0.22 +/- 0.07 mm2; with balloon injury/no radiation 0.37 +/- 0.03 mm2; p < 0.01). Endothelial regeneration, evaluated by transmission and scanning electron micrographs along with uptake of Evans blue dye, was significantly greater in animals that received radiation compared with controls. CONCLUSIONS: Low-dose radiation prevents the occurrence of neointimal hyperplasia after balloon injury and may have a future role in vascular grafting.

Starvation induces differential small bowel luminal amino acid transport.

BACKGROUND: The importance of small intestinal mucosa functions has been emphasized in recent years because gut metabolism becomes better defined. One of the major activities of the enterocyte is amino acid transport, which is important not only for the organism but also for the integrity of the mucosa. Bowel rest during the postoperative period is marked by decreased calorie and protein intake with atrophy of the brush border mucosa. We sought to determine whether active amino acid transport is altered during 72 hours of fasting. METHODS: New Zealand white rabbits were fed (control) or fasted for 72 hours. Brush border membrane vesicles were prepared from scraped jejunal mucosa, and their purity was assessed by marker enzyme enrichment (17- to 25-fold). Transport of tritiated glutamine, arginine, alanine, methylamino-isobutyric acid (MeAIB), and leucine into brush border membrane vesicles was measured by rapid mixing filtration. RESULTS: Fasted animals lost on average 138 +/- 51 gm of body weight. Glutamine and arginine transport were decreased in rabbits fasted for 72 hours compared with controls; alanine, MeAIB, and leucine transport were maintained. The decrease in Glutamine transport was due to a decrease in Vmax (545 +/- 22 versus 836 +/- 93 pmol/mg protein/10 sec; p < 0.05), consistent with a decrease in the number of functional transporter proteins. Km values were similar in both groups (644 +/- 25 versus 624 +/- 18 mumol/L), indicating no change in carrier affinity. CONCLUSION: Differential changes occur in brush border amino acid transport during a 3-day period of bowel rest. The apparent gut nutritive transporters for Glutamine and arginine are decreased, although the gluconeogenic transporters for alanine, MeAIB, and leucine are maintained. These adaptive changes may help explain the difficulties seen in postoperative and critically ill patients on prolonged bowel rest.

Preoperative fasting improves survival after 90% hepatectomy.

OBJECTIVE: To assess whether alterations in preoperative fatty acid oxidation and gluconeogenesis induced by fasting will affect survival and liver regeneration following 90% hepatectomy in the rat. DESIGN: In a randomized, controlled trial, Wistar rats (N = 157) were separated into two groups. Rats in the first group fasted for 24 hours. Rats in the second group were allowed to eat ad libitum until the time of operation. These groups were further randomized to receive either 20% glucose or tap water ad libitum postoperatively. INTERVENTIONS: Ninety percent hepatectomy; 24-hour fast; 5% glucose feeding. MAIN OUTCOME MEASURES: Survival, DNA synthesis in the hepatic remnant along with glucokinase activity (GKA) and glycogen content, serum ketone bodies (KB), free fatty acid (FFA), glucose, and ad libitum glucose consumption (GC) were serially quantified. RESULTS: Fasting rats that were offered glucose (fasted/glucose) after hepatectomy demonstrated better survival at 48 hours than the rats that were fed before the procedure and given glucose following hepatectomy (fed/glucose), 95% vs 52% (P < .05). The fasted/glucose group also had a greater peak rate of DNA synthesis (550 +/- 110 vs 275 +/- 40 disintegrations per minute per 0.001 mg of DNA, P < .05). Survival was poor in both groups when only tap water was offered to the animals after hepatectomy (31% vs 12%). In the fasted/glucose group, GC 1 hour after hepatectomy was greater than that for fed rats (1.3 +/- 0.175 vs 0.73 +/- 0.176 g/h, P < .05), yet GKA was suppressed (3.4 +/- 0.42 vs 8.05 +/- 2.77 nmol/min per milligrams of protein, P < .05). Fasting before hepatectomy and consuming glucose after causes elevations in both FFA (1.26 +/- 0.19 vs 0.82 +/- 0.13 mol/mL., P < .05) and KB (18.96 +/- 2.82 vs 11.4 +/- 3.94 mmol/mL, P < .05). Normal glucose was maintained in the fasted/glucose group, but fell to 63 +/- 14 mg/dL at 8 hours after hepatectomy in the fed/glucose group. CONCLUSIONS: Fasting before hepatectomy shifts energy utilization to fat oxidation and gluconeogenesis, which appears to ameliorate liver failure after hepatectomy in this severe model of hepatic resection.