thromboxane-b2 and Aortic-Aneurysm--Abdominal

Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis. A systematic review of the diversity and outcomes of existing AAA metabonomic research has been performed. Original research studies applying metabonomics to human aneurysmal disease are included. Seven relevant articles were identified: four studies were based on plasma/serum metabolite profiling, and three studies examined aneurysmal tissue. Aminomalonic acid, guanidinosuccinic acid, and glycerol emerge as potential plasma biomarkers of large aneurysm. Lipid profiling improves predictive models of aneurysm presence. Patterns of metabolite variation associated with AAA relate to carbohydrate and lipid metabolism. Perioperative perturbations in metabolites suggest differential systemic inflammatory responses to surgery, generating hypotheses for adjunctive perioperative therapy. Significant limitations include small study sizes, lack of correction for multiple testing false discovery rates, and single time-point sampling. Metabolic profiling carries the potential to identify biomarkers of AAA and elucidate pathways underlying aneurysmal disease. Statistically and methodologically robust studies are required for validation, addressing the hiatus in understanding mechanisms of aneurysm growth and developing effective treatment strategies.

Topics: Aortic Aneurysm, Abdominal; Biomarkers; Disease Progression; Glycerol; Guanidines; Humans; Lipoxins; Malonates; Metabolome; Metabolomics; Prognosis; Succinates; Thromboxane B2

Abdominal aortic aneurysmectomy (AAAectomy) results in a general ischemia-reperfusion syndrome accompanied by an acute rise in pulmonary artery pressure (PAP). We examined whether ulinastatin, a urinary trypsin inhibitor, prevents ischemia-reperfusion injury and increase in PAP after aortic unclamping (XU) during AAAectomy.. Prospective study.. Public, university-affiliated hospital.. Sixteen patients (11 males and 5 females) scheduled for AAAectomy.. The patients received 300000 IU of ulinastatin intravenously before XU (n = 8) or no additional treatment (n = 8) (control). Heart rate, central venous pressure, PAP, pulmonary arterial wedge pressure, arterial pressure, mixed venous oxygen saturation (Sv(O2)), and cardiac output were monitored. Arterial and mixed venous blood samples were analyzed for pH, Pa(CO2), Pa(O2), hemoglobin, and oxygen saturation, and the physiological shunt function (Qs/Qt) were calculated. Plasma concentrations of malondialdehyde, myeloperoxidase, granulocyte elastase, alpha1-antitrypsine, and thromboxane B2 and the stable hydrolysis products of thromboxane A2 were measured. Measurements were conducted before aortic crossclamping (XC) (baseline) and at 10, 30, and 60 minutes after XU.. A significant increase in PAP was observed 10 minutes after XU in the control group but not in the ulinastatin group. At 60 minutes after XU, Qs/Qt values had increased in the control group but had decreased in the ulinastatin group. There were no significant changes in malondialdehyde, thromboxane B2, granulocyte elastase, and alpha1-antitrypsine levels after XU in either group. A significant decrease in the plasma level of myeloperoxidase after XU was found in both groups.. The present study demonstrated that ulinastatin prevents increase in PAP and shunting after XU during AAAectomy.

Topics: Aged; alpha 1-Antitrypsin; Aorta; Aortic Aneurysm, Abdominal; Blood Pressure; Constriction; Female; Glycoproteins; Hemodynamics; Humans; Infusions, Intravenous; Intraoperative Period; Leukocyte Elastase; Male; Malondialdehyde; Peroxidase; Pulmonary Artery; Reperfusion Injury; Thromboxane B2; Trypsin Inhibitors

N-acetylcysteine (NAC) may offer renal and hepatic protection during surgery, but in experimental studies it has been shown to impair coagulation. Since very little is known about the effects of NAC on blood coagulation in surgical patients, we studied its effects during abdominal aortic reconstruction. NAC (a bolus of 150 mg/kg followed by a continuous 24-h infusion of 150 mg/kg) or the same volume of placebo was given intravenously, in a randomized double-blinded fashion, to 20 patients undergoing abdominal aortic aneurysm repair. The haematocrit, platelet count, prothrombin time, thromboelastometry, and platelet aggregation were studied during and after surgery. Total blood loss was also measured. The median (25th-75th percentiles) decrease of the prothrombin time value was 33.0% (30-37%) after NAC treatment and 6.5% (4-8%) after placebo (P<0.001). Postoperative prothrombin time values remained lower in the patients receiving NAC. In thromboelastometry tracings the coagulation time was more prolonged after the bolus of NAC (P=0.02). Platelet aggregation induced with adenosine diphosphate decreased after NAC but not after placebo. Low prothrombin time values before and after bolus infusions were associated with increased blood loss (P=0.008 and P=0.015, respectively). NAC has anticoagulant and platelet-inhibiting properties in patients undergoing major vascular surgery. This abnormal haemostatic activity should be considered when NAC is administered to patients with increased bleeding risk.

Topics: Acetylcysteine; Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Blood Coagulation; Blood Platelets; Double-Blind Method; Female; Free Radical Scavengers; Humans; Male; Middle Aged; Platelet Aggregation; Prothrombin Time; Thrombelastography; Thromboxane B2

To evaluate tissue protection by PGE1 during leg ischemia in patients undergoing aortic surgery.. Randomized, controlled prospective clinical trial.. Single university hospital.. 19 consecutive patients undergoing abdominal aortic aneurysm repair.. Patients received infusions of 30 ng/kg/min of PGE1 or saline.. Hemodynamic variables, lactate, creatine phosphokinase, and thromboxane B2 (TXB2) were measured. In the control group, the decrease in cardiac index (CI) after aortic cross-clamping (AXC) persisted until unclamping together with a decrease in femoral venous O2 content (CfvO2). In the PGE1 group, CI returned to baseline with a trend toward greater CfvO2 levels. During reperfusion in the PGE1 group, O2 consumption and lactate levels exceeded preclamp values. Pulmonary hypertension occurred equally in both groups but did not correlate with TXB2, which was not altered by surgery or by PGE1 infusion.. Intraoperative PGE1 treatment offers no benefit and may exacerbate tissue ischemia during AXC by redistributing microcirculatory flow or limiting cellular oxygen utilization in a manner that overwhelms any possible protective effect.

Topics: Aged; Alprostadil; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Female; Hemodynamics; Humans; Ischemia; Male; Middle Aged; Oxygen; Oxygen Consumption; Prospective Studies; Thromboxane B2

Many circulating haemostatic markers have been investigated in relation to the abdominal aortic aneurysm (AAA) size, growth as well as intraluminal thrombus (ILT) size. However, the results of these studies seem to be uncertain and inconsistent. The first aim of the present study was to compare the haemostatic parameters of fibrinolysis and some of thrombotic markers in patients with AAA and controls. We also examined the relationship between those parameters and both maximum aneurysm diameter and intraluminal thrombus thickness. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), fibrinogen (Fb), D-dimer, prothrombin fragments 1 and 2 (F1+2), thromboxane B2 (TXB2) and lipids profile were measured in 36 patients with AAA and 30 controls. The mean maximum aortic diameter in patients with the AAA was 59±12 mm (range 42-100). The mean ILT thickness was 32±10 mm (range 8-56). Among haemostatic factors, t-PA and D-dimer levels, but not PAI-1, were significantly higher in subjects with the AAA. There was a strong positive correlation between thickness of intraluminal thrombus and maximum aneurysm size (r=0.69, p<0.0001), and the negative relationship between t-PA and ILT thickness (r= -0.53, p=0.001) as well as aneurysm diameter (r= -0.38, p=0.023). Higher plasma concentrations of t-PA and D-dimer support the hypothesis that the secondary fibrinolysis plays an important role in the pathogenesis of the aortic abdominal aneurysm formation. In addition, the negative correlation between t-PA plasma level and ILT thickness suggests that thrombotic/fibrinolysis imbalance may favour accelerated formation of intraluminal thrombus and possibly aneurysm progression.

Topics: Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Biomarkers; Disease Progression; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Severity of Illness Index; Thrombosis; Thromboxane B2; Tissue Plasminogen Activator; Tomography, X-Ray Computed

Our laboratory has previously shown that the levels of secreted prostaglandin E(2) (PGE(2)), Thromboxane B(2) (TxB(2)), and interleukin-6 (IL-6) by aortic explant cultures were high in patients with ruptured abdominal aortic aneurysm (AAA). In the present study, we sought to examine the secretory levels of these inflammatory mediators in aortic explant cultured from a group of AAAs rupturing at a certain size and a group that did not rupture at that size. It was thought that such a comparison might reveal the contribution of those inflammatory mediators to the risk of AAA rupture.. All subjects had abdominal computed tomography (CT) scans to determine the size of the aneurysm, and surgical aortic tissue was collected from both nonruptured AAAs (18 with a mean size of 6 + 0.5 cm [range: 5-7 cm] and 12 with a mean size of 8 + 0.1 cm [range: 7.01-10 cm]) and ruptured AAAs (10 with a mean size of 5.8 + 0.3 cm [range: 5-7 cm] and 10 with a mean size of 7.8 + 0.1 cm [range: 7.01-10 cm]). Aortic explant cultures from different sizes of aneurysms were immediately established and the culture media were collected 72 h later.. The levels of PGE(2), TxB(2), and IL-6 secreted in the cultured medium were quantified by specific enzyme-linked immunosorbent assays (ELISA). The secretary levels of PGE(2), TxB(2), and IL-6 were significantly higher in ruptured AAAs than in nonruptured AAAs of similar diameter. However, there was no correlation between these three inflammatory mediators and the size of AAA.. This study shows that these inflammatory mediators may play a role in the progression toward rupture but may not be responsible for the expansion of AAA.

Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Dinoprostone; Enzyme-Linked Immunosorbent Assay; Humans; In Vitro Techniques; Inflammation Mediators; Interleukin-6; Thromboxane B2; Tomography, X-Ray Computed

To quantify the inflammatory and renal parameters in comparative cohorts of patients undergoing surgical or endovascular repair of abdominal aortic aneurysms (AAAs).. Forty-three patients (41 men; ages 58-81 years) underwent endovascular or conventional aneurysm surgery according to aortic morphology. All patients received a standard general anesthetic and had 12 serial blood and urine samples collected during the perioperative period. Samples underwent analysis for the cytokines interleukin (IL) 1beta tumor necrosis factor-alpha (TNF-alpha), and IL-6. White cell and platelet activation were estimated indirectly by measuring sL-selectin and 11-dehydrothromboxane B2, respectively. The urinary albumin:creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase (NAG) activity were estimated to assess renal injury. Fibrinogen and fibrinogen degradation products were calculated to assess activation of the clotting cascade.. Twenty-three patients underwent endovascular AAA repair and 20 had conventional surgery. Concentrations of IL-6 (p < 0.002) and TNF-alpha (p < 0.0004) were significantly higher in the conventional group. The ACR (p < 0.002) and urinary NAGs (p < 0.0009) were also significantly higher in this group, suggesting greater renal injury. Platelet activity was significantly greater in the endovascular group (p < 0.01), perhaps indicating thrombus organization within the aneurysm sac.. These data suggest that the inflammatory response associated with conventional aneurysm repair is largely obviated by endovascular techniques. This may potentially translate to a lower incidence of multiple organ failure after endovascular surgery.

Topics: Acetylglucosaminidase; Aged; Aged, 80 and over; Albuminuria; Aortic Aneurysm, Abdominal; Blood Platelets; Creatinine; Female; Fibrin Fibrinogen Degradation Products; Humans; Inflammation; Interleukin-1; Interleukin-6; Kidney; L-Selectin; Male; Middle Aged; Minimally Invasive Surgical Procedures; Prospective Studies; Thromboxane B2; Tumor Necrosis Factor-alpha

The aims of this study were to evaluate the effects of aortic clamping and unclamping on neutrophil and monocyte activation and release of plasma mediators in 20 patients undergoing elective aortic aneurysm surgery, and to correlate these findings with pulmonary haemodynamics and gas exchange.. Simultaneous arterial and mixed venous samples were obtained during and after aortic clamping and unclamping.. Neutrophil respiratory burst activity in mixed venous samples increased significantly during the period of aortic clamping. An initial increase in neutrophil CD11b expression in venous blood 5 min after clamp removal was followed by a significant decrease in level of expression. Plasma tumour necrosis factor levels increased at the end of the cross-clamp period and reached a maximum 60 min following reperfusion. There was a significant and sustained rise in plasma thromboxane B2 levels following clamp removal. This increase correlated with the development of increased pulmonary vascular resistance.. This study confirms the central role played by activated neutrophils in the early stages of reperfusion injury and also suggests a role for plasma mediators in mediating cardiopulmonary dysfunction during major vascular surgery.

Topics: Aged; Aortic Aneurysm, Abdominal; Blood Pressure; Constriction; Elective Surgical Procedures; Female; Hemodynamics; Humans; Lung; Lymphocyte Activation; Lymphocyte Count; Macrophage-1 Antigen; Male; Monocytes; Neutrophil Activation; Neutrophils; Reperfusion; Respiratory Burst; Thromboxane B2; Treatment Outcome; Tumor Necrosis Factor-alpha

Aortic aneurysm repair produces inflammatory mediators, neutrophil activation, and remote organ injury. Reperfusion plasma from these patients produces microvascular injury in an ex vivo chemotactic model. This study investigates the mechanism of this injury. Vena caval blood was obtained before and 15 minutes after aortic clamp removal (n = 16) or at laparotomy (n = 10). Plasma or saline solution was introduced into unit dose chambers fixed atop dermabrasions on the back of depilated anesthetized rabbits. Animals were treated with intravenous saline solution (n = 4); made neutropenic with nitrogen mustard (n = 4); pretreated with the xanthine oxidase inhibitor allopurinol (n = 4); or cotreated intravenously with the free radical scavengers superoxide dismutase (SOD) and catalase (n = 4). Three hours later neutrophil counts (polymorphonuclear cells [PMN]/mm3) and activity (free radical production by flow cytometry), protein leakage, and inflammatory mediators (thromboxane [TX] and leukotriene B4 [LTB4]) were measured. In contrast to control plasma in untreated rabbits, reperfusion plasma produced TX and LTB4 generation (1090 +/- 105 and 794 +/- 91 pg/ml, respectively, p < 0.01), PMN accumulation (1636 +/- 210/mm3, p < 0.01) and activation (276 +/- 31 mean fluorescent units), and microvascular permeability (554 +/- 90 micrograms/ml, p < 0.01). Neutropenia (3 +/- 1 PMN/mm3) and cotreatment with SOD and catalase abolished these responses, whereas pretreatment with allopurinol did not. Human reperfusion plasma contains a soluble factor that stimulates free radical generation by rabbit neutrophils to produce a microvascular injury characterized by de novo TX production, neutrophil accumulation and activation, and increased microvascular permeability to protein.

Topics: Allopurinol; Animals; Aortic Aneurysm, Abdominal; Catalase; Cell Movement; Chemotaxis, Leukocyte; Dermabrasion; Humans; Inflammation; Leukocyte Count; Leukotriene B4; Male; Neutrophils; Proteins; Rabbits; Reperfusion Injury; Skin; Superoxide Dismutase; Thromboxane B2