interleukin-8 and Aortic-Aneurysm--Thoracic

In-hospital outcomes are generally acceptable in patients with type B dissection; however, some patients present with undesirable complications, such as aortic expansion and rupture. Excessive inflammation is an independent predictor of adverse clinical outcomes.. We have investigated the underlying mechanisms of catastrophic complications after acute aortic dissection (AAD) in mice.. When angiotensin II was administered in lysyl oxidase inhibitor-preconditioned mice, AAD emerged within 24 hours. The dissection was initiated at the proximal site of the descending thoracic aorta and propagated distally into an abdominal site. Dissection of the aorta caused dilatation, and ≈70% of the mice died of aortic rupture. AAD triggered CXCL1 and granulocyte-colony stimulating factor expression in the tunica adventitia of the dissected aorta, leading to elevation of circulating CXCL1/granulocyte-colony stimulating factor levels. Bone marrow CXCL12 was reduced. These chemokine changes facilitated neutrophil egress from bone marrow and infiltration into the aortic adventitia. Interference of CXCL1 function using an anti-CXCR2 antibody reduced neutrophil accumulation and limited aortic rupture post AAD. The tunica adventitia of the expanded dissected aorta demonstrated high levels of interleukin-6 (IL-6) expression. Neutrophils were the major sources of IL-6, and CXCR2 neutralization significantly reduced local and systemic levels of IL-6. Furthermore, disruption of IL-6 effectively suppressed dilatation and rupture of the dissected aorta without any influence on the incidence of AAD and neutrophil mobilization.. Adventitial CXCL1/granulocyte-colony stimulating factor expression in response to AAD triggers local neutrophil recruitment and activation. This leads to adventitial inflammation via IL-6 and results in aortic expansion and rupture.

Topics: Acute Disease; Adventitia; Aged; Aminopropionitrile; Angiotensin II; Animals; Antibodies, Monoclonal; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Aortic Dissection; Aortic Rupture; Aortography; Chemokine CXCL1; Chemokine CXCL12; Chemotaxis, Leukocyte; Dilatation, Pathologic; Disease Models, Animal; Female; Granulocyte Colony-Stimulating Factor; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Neutrophil Activation; Neutrophil Infiltration; Neutrophils; Receptors, Interleukin-8B; Signal Transduction; Time Factors

Despite its presumed effectiveness and clinical use, the physiology of selective visceral perfusion combined with distal aortic perfusion during open thoracoabdominal aortic surgery has not been characterized. Thus, the aim of this study was to establish a translatable model of thoracic aortic-clamping to assess the effect of selective visceral perfusion with added distal aortic perfusion on local intestinal macrohemodynamics and microhemodynamics, intestinal histopathology, and markers of inflammation and intestinal damage.. A thoracolaparotomy was performed in 15 pigs, and the aorta was exposed, including the origins of celiac trunk and superior mesenteric artery. The animals were divided into three cohorts: control (I), thoracic aortic cross-clamping (II), and thoracic aortic cross-clamping with selective visceral perfusion plus distal aortic perfusion using extracorporeal circulation (III). Macrocirculatory and microcirculatory blood flow was assessed by transit time ultrasound volume flow measurements and fluorescent microspheres. Intestinal ischemia-reperfusion injury was determined by the analysis of perioperative intestinal fatty acid-binding protein (IFABP) and interleukin-8 (IL-8) levels and correlated with histopathologic changes.. Severe intestinal tissue injury and an inflammatory response were observed in cohort II compared with cohort III for IL-8 (38.2 vs 3.56 pg/mL; P = .04). The procedure in cohort III resulted in a flow and pressure-associated intestinal hypoperfusion compared with cohort I in the superior mesenteric artery (mean blood pressure, 24.1 ± 10.4 vs 67.2 ± 7.4 mm Hg; P < .0001; mean flow rates: 353.3 ± 133.8 vs 961.7 ± 310.8 mL/min; P < .0001). This was paralleled in cohort III vs cohort I by a significant mucosal injury (IFABP, 713 ± 307.1 vs 170 ± 115.4 pg/mL; P = .014) despite a profound recruitment of intestinal microcirculation (338% ± 206.7% vs 135% ± 123.7%; P = .05).. This study reports a novel large-animal model of thoracic aortic cross-clamping that allows the study of visceral perfusion strategies. However, we demonstrated with IL-8 and IFABP measurements that thoracoabdominal aortic aneurysm surgery with selective visceral perfusion and distal aortic perfusion is superior to the clamp-and-sew technique, even though small intestinal tissue damage cannot be completely avoided by selective visceral perfusion and distal aortic perfusion. In any case, this model seems to be a platform to evaluate and optimize measures for gut wall protection.

Topics: Animals; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Blood Flow Velocity; Constriction; Extracorporeal Circulation; Fatty Acid-Binding Proteins; Female; Hemodynamics; Interleukin-8; Intestines; Models, Animal; Regional Blood Flow; Reperfusion Injury; Swine; Vascular Surgical Procedures; Viscera

Visceral injury and inflammation are evaluated in patients undergoing extracorporeal circulation (ECC) either with distal aortic perfusion (DAP) during thoracic aortic aneurysm (TAA) repair or DAP and selective organ perfusion (DAP and SP) during thoracoabdominal aortic aneurysm (TAAA) repair.. Visceral hypoperfusion and subsequent visceral injury, mainly to the gut, have been implicated as central events in the development of systemic inflammatory response syndrome (SIRS) and organ dysfunction after major surgery. Patients undergoing DAP or DAP and SP are exposed to artificial visceral perfusion, potentially leading to the development of intestinal injury and systemic inflammation.. To assess visceral injury arteriovenous differences of fatty acid binding proteins were measured for the gut (I-FABP and L-FABP) and left kidney (L-FABP) along with systemic plasma concentrations. Systemic ALT was used as liver injury marker. Plasma IL-6 and IL-8 denoted systemic inflammation.. During ECC systemic I-FABP and L-FABP levels increased in both groups, representing intestinal injury. Significantly elevated levels of I-FABP (P < 0.001) and L-FABP (P < 0.001) were found in the DAP and SP group, after ECC was stopped and normal circulation restored. Liver and renal tubular cell injury was not detected. Significant increases in systemic IL-6 and IL-8 values were measured only in patients undergoing DAP and SP. Additionally, the extent of intestinal injury correlated positively with systemic inflammation.. This study shows the development of intestinal mucosal injury during ECC with DAP or DAP and SP, indicative of insufficient intestinal perfusion. Intestinal injury was associated with a systemic pro-inflammatory response.

Topics: Aortic Aneurysm, Thoracic; Area Under Curve; Extracorporeal Circulation; Fatty Acid-Binding Proteins; Female; Humans; Interleukin-6; Interleukin-8; Intestinal Mucosa; Male; Middle Aged; Systemic Inflammatory Response Syndrome; Viscera

The objective of this study is to evaluate the inflammatory response caused by endovascular stents in the treatment of aortic aneurysms.. Twenty-five patients underwent endovascular stent treatment from March through December 2005. The evolution of mediators (sedimentation velocity, C reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-alpha, intercellular adhesion molecule-1, l-selectin), inflammatory cells (leukocytes, lymphocytes, platelets), serum creatinine and body temperature within preoperative period and in the following postoperative periods--1, 6, 24 and 48 h, 7 days, 1-3 months, was analyzed. In order to achieve statistic significance, Friedman test and Wilcoxon test were used, with index of significance of 5% (p<0.05).. Peak values of sedimentation velocity, C reactive protein and interleukin-6 were observed at 7 days (p<0.0001), 48 h (p<0.0001) and 24h (p<0.0001), respectively. Tumor necrosis factor-alpha and interleukin-8 did not show statistically significant variability during the entire follow-up. In terms of intercellular adhesion molecule-1 and l-selectin, their expressive values were found in late phase of follow-up, although without statistical significance. Elevation of leukocytes count occurred in premature phase of follow-up (p<0.0001), while lymphocyte and platelet count occurred in a late phase of follow-up (p<0.0001). Serum levels of creatinine did not show significant variability during follow-up. The period between 24 and 48 h corresponded to major frequency for fever (p<0.0001).. Individual mediators analysis and inflammatory cells demonstrated variability of their values during postoperative follow-up. This could help in the analysis of the inflammatory response evolution caused by endovascular stent treatment for aortic aneurysms in premature and late phases after implantation of the vascular prosthesis.

Topics: Adult; Aged; Aged, 80 and over; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Blood Vessel Prosthesis Implantation; Female; Follow-Up Studies; Humans; Inflammation; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; L-Selectin; Male; Middle Aged; Stents; Tumor Necrosis Factor-alpha

Cardiopulmonary bypass (CPB) is believed to cause postoperative lung dysfunction. To more closely examine the inflammatory processes occurring in the airways during CPB, we serially measured inflammatory mediators, with the assistance of a new bronchoscopic microsample probe, in 11 patients undergoing repair of aortic arch aneurysms. Epithelial lining fluid (ELF) and arterial blood were sampled simultaneously after induction of anesthesia, at the time of pulmonary reperfusion, and at the end of surgery. A decrease in the PaO2/FiO2 ratio was observed at the end of surgery (P = 0.029). Although the ELF concentrations of interleukin (IL)-8, IL-6, and neutrophil elastase had increased significantly at the end of surgery (median = 23,200, 1818, and 12,900 microg/mL, respectively), they did not correlate with the degree of hypoxemia. Neutrophil elastase increased significantly at the time of pulmonary reperfusion, before IL-8 and IL-6, and independently of blood transfusions. At the end of surgery, IL-6 in ELF correlated with total blood transfusion volume (rho = 0.731, P = 0.011). These results indicate that a neutrophil-derived inflammatory response is activated in the airway in the early phase of CPB.

Topics: Aged; Aged, 80 and over; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Cardiopulmonary Bypass; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukocyte Elastase; Male; Neutrophils

The purpose of this study was to semiquantify the magnitude of surgical stress in patients undergoing aortic surgery by measuring inflammatory responses perioperatively, focusing on cytokine secretion. Serum concentrations of interleukin (IL) 1alpha, IL-6, IL-8, and tumor necrotizing factor (TNF) Alpha were measured in patients undergoing abdominal or thoracic aortic aneurysmectomy preoperatively and periodically thereafter for 2 weeks. Urinary trypsin inhibitor (UTI/Cr) and C-reactive protein (CRP) concentration and the systemic inflammatory response syndrome (SIRS) score also were determined. Indices of inflammation and cytokine concentrations peaked at 1-3 days after surgery and decreased thereafter; however, IL-8 increased again after day 7. Concentrations of IL-8, UTI/Cr, and CRP and the SIRS score were still higher 14 days after surgery than preoperatively. The maximum concentrations of IL-6 and IL-8 were higher after thoracic than abdominal aortic repair; however, the maximum values of cytokines were not correlated with operative factors in all patients. A patient suffering from graft infection showed an increase in cytokine concentrations on day 7. The inflammatory response does not return to preoperative values within 2 weeks of surgery in patients undergoing thoracic or abdominal aortic aneurysm repair. The prolonged secretion of IL-8 suggests a host reaction to the synthetic prosthesis. A large increase in inflammatory cytokines on day 7 may indicate infection of the vascular graft.

Topics: Adult; Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Blood Vessel Prosthesis Implantation; C-Reactive Protein; Female; Glycoproteins; Humans; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Postoperative Period; Stress, Physiological; Tumor Necrosis Factor-alpha