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PS218. Effect of Remote Ischemic Preconditioning in Liver Ischemia—Reperfusion Injury Produced by Supraceliac Aortic Cross-clamping in a Swine Model of Open Repair of Thoracoabdominal Aortic Aneurysm
JOURNAL OF VASCULAR SURGERY Volume 51, Number 11S
MMP-2 activity by ⫺8 ⫾ 1% (n ⫽ 2), Est-stimulated migration by ⫺34 ⫾ 2% (p ⬍ 0.01; n ⫽ 4-8), and Est-stimulated proliferation by ⫺9 ⫾ 3% (p ⬍ 0.05; n ⫽ 3), indicating they occur in an ERK1/2 dependent manner. Conclusions: Estrogen stimulates the cellular processes of IH development via ERK1/2 dependent signaling. Inhibition of ERK1/2 results in downregulation of Est-mediated MMP activity and Est-induced VS MC migration and proliferation. Future studies will include targeted ERK1/2 silencing to assay a possible mechanism for effective IH inhibition. Understanding the signaling mechanisms involved in hormone-mediated IH development could provide a basis for therapeutic strategies of inhibition. Author Disclosures: D. C. Cassada: Nothing to disclose; M. B. Freeman: Nothing to disclose; M. H. Goldman: Nothing to disclose; O. Grandas: Nothing to disclose; S. S. Kirkpatrick: Nothing to disclose; D. J. Mountain: Nothing to disclose; S. L. Stevens: Nothing to disclose; M. Tummers: Nothing to disclose.
PS216. Short-term Diet Induced Obesity Drives Negative Vein Graft Remodeling Peng Yu, Binh Nguyen, Ming Tao, Christina Campagna, James A. Lederer, C. K. Ozaki. Surgery, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA Objectives: Inflammatory pathways are associated with vein graft failure. Short-term high-fat feeding induces a proinflammatory state in perivascular adipocytes, but the longerterm impact of such dietary induced dysfunction on clinically relevant vascular events is unclear. We tested the hypothesis that the inflammatory phenotype resulting from diet induced obesity (DIO) drives accelerated vein graft failure (increased intimal hyperplasia, enhanced negative wall remodeling). Methods: Male 9-week-old DIO mice (n ⫽ 5; 3 wks of high caloric diet) and controls (n ⫽ 5) underwent isograft (IVC from same diet donor) unilateral carotid interposition vein graft with a focal mid-graft stenosis. Perfusion fixed vein graft was harvested 4 wks later. DIO/control mice also underwent blood, spleen, and adipose cell harvest for immune profiling (flow cytometry). Results: Despite a 40% larger body size, DIO mice had 34% smaller residual vein graft lumens (p ⫽ 0.02). Lumen loss was not due to accelerated intimal hyperplasia, or other differentials in wall thickness (all layer thicknesses and intima/media ratio were equivalent), but rather acceleration of overall negative wall remodeling (cross sectional wall area 47% smaller, p ⫽ 0.03; outer vein graft perimeter 19% shorter, p ⫽ 0.01). Resting blood and spleen immune cell profiles were similar; DIO fat held significantly more NK cells, macrophages, and dendritic cells. Conclusions: These findings highlight negative wall remodeling as a factor leading to vein graft failure, and provide direct evidence that short-term dietary alterations
Abstracts 75S
in the mammalian metabolic milieu can have lasting implications relating to acute vascular interventions. Author Disclosures: C. Campagna: Nothing to disclose; J. A. Lederer: Nothing to disclose; B. Nguyen: Nothing to disclose; C. K. Ozaki: Nothing to disclose; M. Tao: Nothing to disclose; P. Yu: Nothing to disclose.
PS218. Effect of Remote Ischemic Preconditioning in Liver Ischemia—Reperfusion Injury Produced by Supraceliac Aortic Cross-clamping in a Swine Model of Open Repair of Thoracoabdominal Aortic Aneurysm Andreas M. Lazaris1, Georgios Martikos1, Alkistis Kapelouzou2, Katerina Pavlaki2, Michalis Peroulis1, John Kakisis1, Spyros Vasdekis1, Panagiotis Karagiannakos2, Gabriel Karatzas1, Anastasios Maheras1, Alkiviadis Kostakis2, Theodore Liakakos1. 13rd Surgical Department, University of Athens, Attikon Teaching Hospital, Athens, Greece; 2 Biomedical Research Foundation, Academy of Athens, Department of Surgery, Athens, Greece Objectives: Visceral ischemia is inevitable during the open repair of a thoracoabdominal aortic aneurysm (TAAA). Remote ischemic preconditioning (RIPC) has been described as a potential protective measure from ischemia - reperfusion injury (IRI) in various distal tissues. The aim of this experimental study has been to identify any protective effect of RIPC in liver IRI caused during aortic temporal occlusion as performed during a TAAA open repair. Methods: Three groups of 6 swines each underwent a 30 minutes of aortic supraceliac cross-clamping after a left sided visceral rotation. Liver functional and pathological status was assessed 24 hours after ischemia. The first group was the sham group, the second group was the ischemia reperfusion (IR) group and the third one was the RIPC group, where remote ischemic preconditioning with a temporary occlusion of the infrarenal aorta was performed before supraceliac aortic cross-clamping. Statistical analysis was done with parametric and non-parametric techniques. Results: Attenuation of liver damage was noted in the RIPC group as compared to the IR group. Statistically significant reduced values of liver functional markers were found at 24 hours post ischemia between the two groups as follows: alanine aminotransferase (ALT), 36.6 ⫾ 13.5 IU/L in RIPC group vs 58.6 ⫾ 12.5 IU/L in IR group (p ⫽ 0.01), and aspartate transaminase (AST), 43.4 ⫾ 14.7 IU/L in RIPC group vs 119.5 ⫾ 25.7 IU/L in IR group (p ⬍ 0.001). With regard to the pathological liver status, the median values of the parameters examined in RIPC and IR groups were respectively: congestion 1 vs 2 (p ⫽ 0.05), inflammation 1 vs 2 (p ⫽ 0.02), necrosis 0 vs 2 (p ⫽ 0.02). No difference was found in liver degeneration (1 vs 1, p ⫽ NS). Conclusions: There is considerable evidence that RIPC with a temporary infrarenal aortic occlusion can reduce the occasionally hazardous liver IRI that is caused during a TAA open repair.
JOURNAL OF VASCULAR SURGERY June Supplement 2010
76S Abstracts
Author Disclosures: J. Kakisis: Nothing to disclose; A. Kapelouzou: Nothing to disclose; P. Karagiannakos: Nothing to disclose; G. Karatzas: Nothing to disclose; A. Kostakis: Nothing to disclose; A. M. Lazaris: Nothing to disclose; T. Liakakos: Nothing to disclose; A. Maheras: Nothing to disclose; G. Martikos: Nothing to disclose; K. Pavlaki: Nothing to disclose; M. Peroulis: Nothing to disclose; S. Vasdekis: Nothing to disclose.
PS220. Peroxiredoxin-2 as Circulating Biomarkers for Small Abdominal Aortic Aneurysm Progression: A Proteomic View Sigitas Urbonavicius1, Jes S. Lindholt1, Grazina Urbonaviciene1, Eskild W. Henneberg1, Bent Honoré2. 1Department of Vascular Surgery, Regionshospital Viborg, Viborg, Denmark; 2Institute of Medical Biochemistry, University of Aarhus, Aarhus, Denmark Objectives: Proteomic is evolving as an important research technique in cardiovascular disease. Identification of circulating biomarkers for the progression and rupture of abdominal aortic aneurysms (AAA) could improved selection of patients to AAA repair. We aimed to investigate the basic serum proteins composition and to associate with different AAA expansion rate by proteomic. Methods: A proteomic approach was used consisting of two-dimensional gel electrophoresis (2D-PAGE) and mass spectrometry (MS) to identify differentially expressed proteins in sera from 15 AAA operated patients. The percentage volumes of protein-spots with AAA were determined by computerized imaging, and associated with AAA expansion rate. Relevant protein-spots were in-gel digested and identified by liquid chromatography - tandem mass spectrometry (LC-MS/MS). Results: Five hundred and thirty-two spots were demonstrated on the gels. Fourteen protein spots correlated strongly with AAA expansion rate (rho⬎⫹/-0.6). Nine protein spots showed positive and negative correlation represented fragments of albumin, highly abundant in serum. The five negatively correlated spots were apolipoprotein A-IV (rho ⫽ ⫺0.67, p ⫽ 0.038); fibrinogen--chain (rho ⫽ ⫺0.66, p ⫽ 0.036); haptoglobin in two spots (rho ⫽ ⫺0.66, p ⫽ 0.038 and rho ⫽ ⫺0.65, p ⫽ 0.042); Ig-␣-1 or 2 chain C (rho ⫽ ⫺0.76, p ⫽ 0.011) and peroxiredoxin-2 (rho ⫽ ⫺0.62, p ⫽ 0.05). Interestingly, in our previous study peroxiredoxin-2 was up-regulated 8.1fold in the ruptured AAA group compared with nonruptured AAA as determined by 2D-PAGE. Western blot analysis confirmed the significant up-regulation of peroxiredoxin-2 in ruptured aortic tissue. Conclusions: Collectively studies provide support for the hypothesis that oxidative stress is an important component in formation and enlargement of AAA through activation of MMPs and induction of apoptosis within the aortic wall. Larger studies are required to confirm the potential and clinical role of peroxiredoxin-2 in AAA formation.
Author Disclosures: E. W. Henneberg: Nothing to disclose; B. Honoré: Nothing to disclose; J. S. Lindholt: Nothing to disclose; G. Urbonaviciene: Nothing to disclose; S. Urbonavicius: Nothing to disclose. C11: Poster Presentation II -Research (2) PS222. An Aortic Model for Physiological Assessment of Aortic Stent-grafts and In Vitro Compliance Measurement Mital Y. Desai1, Max Ahmed1, Arnold Darbyshire1, Alexander Seifalian1, George Hamilton2. 1University College London Division of Surgery and Interventional Science, Royal Free Hospital, London, United Kingdom; 2Vascular Surgery, Royal Free Hampstead NHS Trust, London, United Kingdom Objectives: Current models of aortic aneurysms for stent-graft assessment and development are anatomically correct but do not match physiological properties of living aortic tissue. Our aim was to manufacture new aortic model with physiological properties from biocompatible and viscoelastic polymer developed by our group. Methods: Porcine abdominal aortas were acquired to establish values for compliance. Aortic model was manufactured using nanocomposite polymer based on polyhedral oligomeric silsesquioxanes (POSS) and poly (carbonate-urea)-urethane (PCU). Commercially available latex mock aorta was used for comparison. A pulsatile flow phantom perfused aortas and synthetic tubes at physiological pulse pressure and flow. Intraluminal pressure was measured using Millar Mikro-tip catheter transducer and vessel wall motion was determined with duplex ultrasonography. Diametrical compliance and stiffness index were calculated over mean pressures 30, 60, 90 and 110 mm Hg. Results: Flow circuit haemodynamics including pulse pressure, flow rate, perfusate temperature and viscosity were similar for porcine aorta and synthetic tubes. Compliance of aorta ranged from 2.97 ⫾ 0.72 (mean ⫾ s.d.) to 1.42 ⫾ 0.37 percent per mm of HgX10-2. Using one-way analysis of variance and Bonferroni Multiple Comparison Test, polymer model was significantly more compliant (range 3.66 ⫾ 1.05 to 2.72 ⫾ 0.28; p ⬍ 0.05*) as compared to porcine aorta with no significant difference in elastic stiffness (mean difference 30.27, p⬎0.05) but similar anisotropic behaviour. Latex tubes exhibited compliance similar to aorta (0.87 ⫾ 0.24 to 0.86 ⫾ 0.2; p ⬎ 0.05) only at low pressures however on increase in pressure from mean of 90 mm Hg, these tubes failed by significant distension. Conclusions: We have developed physiologically relevant aortic model exhibiting compatible anatomy, compliance and viscoelasticity which could be used for long-term fatigue analysis of vascular stents and grafts. The commercially available latex mock aortas can fail at physiological pressures. Author Disclosures: M. Ahmed: Nothing to disclose; A. Darbyshire: Nothing to disclose; M. Y. Desai: Nothing to
MMP-2 activity by ⫺8 ⫾ 1% (n ⫽ 2), Est-stimulated migration by ⫺34 ⫾ 2% (p ⬍ 0.01; n ⫽ 4-8), and Est-stimulated proliferation by ⫺9 ⫾ 3% (p ⬍ 0.05; n ⫽ 3), indicating they occur in an ERK1/2 dependent manner. Conclusions: Estrogen stimulates the cellular processes of IH development via ERK1/2 dependent signaling. Inhibition of ERK1/2 results in downregulation of Est-mediated MMP activity and Est-induced VS MC migration and proliferation. Future studies will include targeted ERK1/2 silencing to assay a possible mechanism for effective IH inhibition. Understanding the signaling mechanisms involved in hormone-mediated IH development could provide a basis for therapeutic strategies of inhibition. Author Disclosures: D. C. Cassada: Nothing to disclose; M. B. Freeman: Nothing to disclose; M. H. Goldman: Nothing to disclose; O. Grandas: Nothing to disclose; S. S. Kirkpatrick: Nothing to disclose; D. J. Mountain: Nothing to disclose; S. L. Stevens: Nothing to disclose; M. Tummers: Nothing to disclose.
PS216. Short-term Diet Induced Obesity Drives Negative Vein Graft Remodeling Peng Yu, Binh Nguyen, Ming Tao, Christina Campagna, James A. Lederer, C. K. Ozaki. Surgery, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA Objectives: Inflammatory pathways are associated with vein graft failure. Short-term high-fat feeding induces a proinflammatory state in perivascular adipocytes, but the longerterm impact of such dietary induced dysfunction on clinically relevant vascular events is unclear. We tested the hypothesis that the inflammatory phenotype resulting from diet induced obesity (DIO) drives accelerated vein graft failure (increased intimal hyperplasia, enhanced negative wall remodeling). Methods: Male 9-week-old DIO mice (n ⫽ 5; 3 wks of high caloric diet) and controls (n ⫽ 5) underwent isograft (IVC from same diet donor) unilateral carotid interposition vein graft with a focal mid-graft stenosis. Perfusion fixed vein graft was harvested 4 wks later. DIO/control mice also underwent blood, spleen, and adipose cell harvest for immune profiling (flow cytometry). Results: Despite a 40% larger body size, DIO mice had 34% smaller residual vein graft lumens (p ⫽ 0.02). Lumen loss was not due to accelerated intimal hyperplasia, or other differentials in wall thickness (all layer thicknesses and intima/media ratio were equivalent), but rather acceleration of overall negative wall remodeling (cross sectional wall area 47% smaller, p ⫽ 0.03; outer vein graft perimeter 19% shorter, p ⫽ 0.01). Resting blood and spleen immune cell profiles were similar; DIO fat held significantly more NK cells, macrophages, and dendritic cells. Conclusions: These findings highlight negative wall remodeling as a factor leading to vein graft failure, and provide direct evidence that short-term dietary alterations
Abstracts 75S
in the mammalian metabolic milieu can have lasting implications relating to acute vascular interventions. Author Disclosures: C. Campagna: Nothing to disclose; J. A. Lederer: Nothing to disclose; B. Nguyen: Nothing to disclose; C. K. Ozaki: Nothing to disclose; M. Tao: Nothing to disclose; P. Yu: Nothing to disclose.
PS218. Effect of Remote Ischemic Preconditioning in Liver Ischemia—Reperfusion Injury Produced by Supraceliac Aortic Cross-clamping in a Swine Model of Open Repair of Thoracoabdominal Aortic Aneurysm Andreas M. Lazaris1, Georgios Martikos1, Alkistis Kapelouzou2, Katerina Pavlaki2, Michalis Peroulis1, John Kakisis1, Spyros Vasdekis1, Panagiotis Karagiannakos2, Gabriel Karatzas1, Anastasios Maheras1, Alkiviadis Kostakis2, Theodore Liakakos1. 13rd Surgical Department, University of Athens, Attikon Teaching Hospital, Athens, Greece; 2 Biomedical Research Foundation, Academy of Athens, Department of Surgery, Athens, Greece Objectives: Visceral ischemia is inevitable during the open repair of a thoracoabdominal aortic aneurysm (TAAA). Remote ischemic preconditioning (RIPC) has been described as a potential protective measure from ischemia - reperfusion injury (IRI) in various distal tissues. The aim of this experimental study has been to identify any protective effect of RIPC in liver IRI caused during aortic temporal occlusion as performed during a TAAA open repair. Methods: Three groups of 6 swines each underwent a 30 minutes of aortic supraceliac cross-clamping after a left sided visceral rotation. Liver functional and pathological status was assessed 24 hours after ischemia. The first group was the sham group, the second group was the ischemia reperfusion (IR) group and the third one was the RIPC group, where remote ischemic preconditioning with a temporary occlusion of the infrarenal aorta was performed before supraceliac aortic cross-clamping. Statistical analysis was done with parametric and non-parametric techniques. Results: Attenuation of liver damage was noted in the RIPC group as compared to the IR group. Statistically significant reduced values of liver functional markers were found at 24 hours post ischemia between the two groups as follows: alanine aminotransferase (ALT), 36.6 ⫾ 13.5 IU/L in RIPC group vs 58.6 ⫾ 12.5 IU/L in IR group (p ⫽ 0.01), and aspartate transaminase (AST), 43.4 ⫾ 14.7 IU/L in RIPC group vs 119.5 ⫾ 25.7 IU/L in IR group (p ⬍ 0.001). With regard to the pathological liver status, the median values of the parameters examined in RIPC and IR groups were respectively: congestion 1 vs 2 (p ⫽ 0.05), inflammation 1 vs 2 (p ⫽ 0.02), necrosis 0 vs 2 (p ⫽ 0.02). No difference was found in liver degeneration (1 vs 1, p ⫽ NS). Conclusions: There is considerable evidence that RIPC with a temporary infrarenal aortic occlusion can reduce the occasionally hazardous liver IRI that is caused during a TAA open repair.
JOURNAL OF VASCULAR SURGERY June Supplement 2010
76S Abstracts
Author Disclosures: J. Kakisis: Nothing to disclose; A. Kapelouzou: Nothing to disclose; P. Karagiannakos: Nothing to disclose; G. Karatzas: Nothing to disclose; A. Kostakis: Nothing to disclose; A. M. Lazaris: Nothing to disclose; T. Liakakos: Nothing to disclose; A. Maheras: Nothing to disclose; G. Martikos: Nothing to disclose; K. Pavlaki: Nothing to disclose; M. Peroulis: Nothing to disclose; S. Vasdekis: Nothing to disclose.
PS220. Peroxiredoxin-2 as Circulating Biomarkers for Small Abdominal Aortic Aneurysm Progression: A Proteomic View Sigitas Urbonavicius1, Jes S. Lindholt1, Grazina Urbonaviciene1, Eskild W. Henneberg1, Bent Honoré2. 1Department of Vascular Surgery, Regionshospital Viborg, Viborg, Denmark; 2Institute of Medical Biochemistry, University of Aarhus, Aarhus, Denmark Objectives: Proteomic is evolving as an important research technique in cardiovascular disease. Identification of circulating biomarkers for the progression and rupture of abdominal aortic aneurysms (AAA) could improved selection of patients to AAA repair. We aimed to investigate the basic serum proteins composition and to associate with different AAA expansion rate by proteomic. Methods: A proteomic approach was used consisting of two-dimensional gel electrophoresis (2D-PAGE) and mass spectrometry (MS) to identify differentially expressed proteins in sera from 15 AAA operated patients. The percentage volumes of protein-spots with AAA were determined by computerized imaging, and associated with AAA expansion rate. Relevant protein-spots were in-gel digested and identified by liquid chromatography - tandem mass spectrometry (LC-MS/MS). Results: Five hundred and thirty-two spots were demonstrated on the gels. Fourteen protein spots correlated strongly with AAA expansion rate (rho⬎⫹/-0.6). Nine protein spots showed positive and negative correlation represented fragments of albumin, highly abundant in serum. The five negatively correlated spots were apolipoprotein A-IV (rho ⫽ ⫺0.67, p ⫽ 0.038); fibrinogen--chain (rho ⫽ ⫺0.66, p ⫽ 0.036); haptoglobin in two spots (rho ⫽ ⫺0.66, p ⫽ 0.038 and rho ⫽ ⫺0.65, p ⫽ 0.042); Ig-␣-1 or 2 chain C (rho ⫽ ⫺0.76, p ⫽ 0.011) and peroxiredoxin-2 (rho ⫽ ⫺0.62, p ⫽ 0.05). Interestingly, in our previous study peroxiredoxin-2 was up-regulated 8.1fold in the ruptured AAA group compared with nonruptured AAA as determined by 2D-PAGE. Western blot analysis confirmed the significant up-regulation of peroxiredoxin-2 in ruptured aortic tissue. Conclusions: Collectively studies provide support for the hypothesis that oxidative stress is an important component in formation and enlargement of AAA through activation of MMPs and induction of apoptosis within the aortic wall. Larger studies are required to confirm the potential and clinical role of peroxiredoxin-2 in AAA formation.
Author Disclosures: E. W. Henneberg: Nothing to disclose; B. Honoré: Nothing to disclose; J. S. Lindholt: Nothing to disclose; G. Urbonaviciene: Nothing to disclose; S. Urbonavicius: Nothing to disclose. C11: Poster Presentation II -Research (2) PS222. An Aortic Model for Physiological Assessment of Aortic Stent-grafts and In Vitro Compliance Measurement Mital Y. Desai1, Max Ahmed1, Arnold Darbyshire1, Alexander Seifalian1, George Hamilton2. 1University College London Division of Surgery and Interventional Science, Royal Free Hospital, London, United Kingdom; 2Vascular Surgery, Royal Free Hampstead NHS Trust, London, United Kingdom Objectives: Current models of aortic aneurysms for stent-graft assessment and development are anatomically correct but do not match physiological properties of living aortic tissue. Our aim was to manufacture new aortic model with physiological properties from biocompatible and viscoelastic polymer developed by our group. Methods: Porcine abdominal aortas were acquired to establish values for compliance. Aortic model was manufactured using nanocomposite polymer based on polyhedral oligomeric silsesquioxanes (POSS) and poly (carbonate-urea)-urethane (PCU). Commercially available latex mock aorta was used for comparison. A pulsatile flow phantom perfused aortas and synthetic tubes at physiological pulse pressure and flow. Intraluminal pressure was measured using Millar Mikro-tip catheter transducer and vessel wall motion was determined with duplex ultrasonography. Diametrical compliance and stiffness index were calculated over mean pressures 30, 60, 90 and 110 mm Hg. Results: Flow circuit haemodynamics including pulse pressure, flow rate, perfusate temperature and viscosity were similar for porcine aorta and synthetic tubes. Compliance of aorta ranged from 2.97 ⫾ 0.72 (mean ⫾ s.d.) to 1.42 ⫾ 0.37 percent per mm of HgX10-2. Using one-way analysis of variance and Bonferroni Multiple Comparison Test, polymer model was significantly more compliant (range 3.66 ⫾ 1.05 to 2.72 ⫾ 0.28; p ⬍ 0.05*) as compared to porcine aorta with no significant difference in elastic stiffness (mean difference 30.27, p⬎0.05) but similar anisotropic behaviour. Latex tubes exhibited compliance similar to aorta (0.87 ⫾ 0.24 to 0.86 ⫾ 0.2; p ⬎ 0.05) only at low pressures however on increase in pressure from mean of 90 mm Hg, these tubes failed by significant distension. Conclusions: We have developed physiologically relevant aortic model exhibiting compatible anatomy, compliance and viscoelasticity which could be used for long-term fatigue analysis of vascular stents and grafts. The commercially available latex mock aortas can fail at physiological pressures. Author Disclosures: M. Ahmed: Nothing to disclose; A. Darbyshire: Nothing to disclose; M. Y. Desai: Nothing to