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Synergistic wound healing promoting effects of adenosine and nitric oxide
Vol. 221, No. 4S2, October 2015
Scientific Poster Presentations: 2015 Clinical Congress
e145
increase was noted in age >16 years over time. Only 3.7% of patients with severe TBI had a protective helmet. Logistic regression identified age >10 years, male gender, and no helmet use as independent risk factors for severe TBI.
subunits. Additionally, hemolyzed red blood cells (RBCs) have been shown to increase fibrinolysis in vitro, although this mechanism is unclear. We hypothesize that hemoglobin A or its subunits potentiate fibrinolysis in TIC.
CONCLUSIONS: Helmet use in patients with SRI is low, despite clear evidence that it is protective against severe TBI. Older children are at increased risk of severe TBI after SRI and more targeted preventive education is needed.
METHODS: Blood was obtained from 3 donors. A tPA challenge thromboelastogram (TEG) was performed on each citrated sample in the presence of increasing concentrations of HbA, beta globin subunit, and alpha globin subunit. Fibrinolysis was measured using the LY30. Data were analyzed using the Kruskal-Wallis test with Dunn’s test for multiple comparisons.
Synergistic wound healing promoting effects of adenosine and nitric oxide Zoltan H Nemeth, MD, PhD, Jaroslaw W Bilaniuk, MD, FACS, John M Adams, MD, FACS, Louis T DiFazio, MD, FACS, Rolando H Rolandelli, MD, FACS Morristown Medical Center, Morristown, NJ INTRODUCTION: Wound healing is a highly organized biological process involving inflammation, cell proliferation, matrix deposition and tissue remodeling. Impaired wound healing is well documented in mice lacking adenosine A2A receptor. In addition, the rapid activation of inducible nitric oxide synthase (iNOS) has been reported during wound repair. Functioning vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 (HIF-1) are also required for normal wound healing. Our hypothesis was that high tissue levels of adenosine released from damaged cells and nitric oxide produced by iNOS would promote wound healing through the induction of VEGF and HIF-1. METHODS: Using an in vitro wound model, messenger RNA (mRNA) and total protein samples were extracted from wounded fibroblasts treated with adenosine, NO, both or vehicle. The purified mRNA samples were used for real time PCR while protein extracts from the same samples were analyzed by Western blotting or enzyme-linked immunosorbent assay (ELISA). RESULTS: mRNA expression levels of VEGF and HIF-1 were significantly higher in wounded fibroblasts treated with either adenosine or NO, but the highest levels occurred when treated with the combination of both. Exposure of wounded fibroblasts to this combination resulted in increased phosphorylation of p38 mitogen-activated protein kinase. CONCLUSIONS: Since VEGF and HIF-1 promote tissue adaptation and angiogenesis, high levels of adenosine and NO, localized around damaged tissue, may be beneficial for wound healing. The alpha subunit of hemoglobin potentiates fibrinolysis Alexander Morton Colorado, Ernest E Moore, MD, FACS, Hunter B Moore, MD, Christopher C Silliman, MD, PhD, Eduardo Gonzalez, MD, Anirban Banerjee, PhD University of Colorado, Aurora, CO INTRODUCTION: Systemic hyperfibrinolysis is an important component of trauma induced coagulopathy (TIC). Proteomic analysis of plasma from patients experiencing TIC has shown an elevation in hemolysis products, including hemoglobin and its
RESULTS: Fibrinolysis was enhanced in the alpha group in a concentration-dependent fashion (p¼0.0333). Median LY30 were 36% (control), 55% (200 nM), 57% (500 nM), and 64% (800nM). Fibrinolysis was unchanged by the addition of beta subunit (p¼0.9286). Median LY30 were 30% (baseline), 34% (200 nM), and 37% (500nM). At the 500 nM dose, LY30 was statistically elevated in the alpha group compared to beta group (57% vs 37%; p¼0.0125). HbA did not change fibrinolysis, even at 10-fold and 100-fold higher concentrations (p¼0.4798). Median LY30 were 25% (baseline), 17% (1.25 mM), 17% (2.5 mM), 18% (5 mM), 19% (10 mM), and 20% (20 mM). CONCLUSIONS: Fibrinolysis is enhanced in a concentrationdependent fashion by the alpha globin subunit, but not by the beta globin subunit, or HbA. These data, coupled with our findings of increased free HbA and subunit concentrations in TIC suggest alpha globin chain as a potential mediator likely involving the plasmin system. The impact of temporal, environmental, and sociocultural factors on blunt and penetrating trauma admission volumes: review of 41,613 patient admissions Vincent Cheng, Regan J Berg, MD, Dimitra Skiada, MD, Obi T Okoye, MD, Robert G Fovell, PhD, Pedro G Teixeira, MD, Demetrios Demetriades, MD, PhD, Kenji Inaba, MD, FACS Los Angeles County University of Southern California, Los Angeles, CA INTRODUCTION: The ability to predict periods of significantly increased demand for trauma care has important implications for healthcare resource planning and patient safety. Previous attempts to delineate factors associated with increased admission volumes have suffered from methodological limitations, including the frequent assessment of blunt and penetrating trauma together, neglecting these mechanisms’ different behavioral correlates. METHODS: All trauma admissions between January 1, 2006 and December 31, 2013 were reviewed and categorized by mechanism, the presence of severe injury (ISS >15), and operative need. Poisson regression evaluated trauma volume incidence rate ratios as a function of temporal, environmental, and sociocultural (holidays, celebrations and sporting events) factors.
Scientific Poster Presentations: 2015 Clinical Congress
e145
increase was noted in age >16 years over time. Only 3.7% of patients with severe TBI had a protective helmet. Logistic regression identified age >10 years, male gender, and no helmet use as independent risk factors for severe TBI.
subunits. Additionally, hemolyzed red blood cells (RBCs) have been shown to increase fibrinolysis in vitro, although this mechanism is unclear. We hypothesize that hemoglobin A or its subunits potentiate fibrinolysis in TIC.
CONCLUSIONS: Helmet use in patients with SRI is low, despite clear evidence that it is protective against severe TBI. Older children are at increased risk of severe TBI after SRI and more targeted preventive education is needed.
METHODS: Blood was obtained from 3 donors. A tPA challenge thromboelastogram (TEG) was performed on each citrated sample in the presence of increasing concentrations of HbA, beta globin subunit, and alpha globin subunit. Fibrinolysis was measured using the LY30. Data were analyzed using the Kruskal-Wallis test with Dunn’s test for multiple comparisons.
Synergistic wound healing promoting effects of adenosine and nitric oxide Zoltan H Nemeth, MD, PhD, Jaroslaw W Bilaniuk, MD, FACS, John M Adams, MD, FACS, Louis T DiFazio, MD, FACS, Rolando H Rolandelli, MD, FACS Morristown Medical Center, Morristown, NJ INTRODUCTION: Wound healing is a highly organized biological process involving inflammation, cell proliferation, matrix deposition and tissue remodeling. Impaired wound healing is well documented in mice lacking adenosine A2A receptor. In addition, the rapid activation of inducible nitric oxide synthase (iNOS) has been reported during wound repair. Functioning vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 (HIF-1) are also required for normal wound healing. Our hypothesis was that high tissue levels of adenosine released from damaged cells and nitric oxide produced by iNOS would promote wound healing through the induction of VEGF and HIF-1. METHODS: Using an in vitro wound model, messenger RNA (mRNA) and total protein samples were extracted from wounded fibroblasts treated with adenosine, NO, both or vehicle. The purified mRNA samples were used for real time PCR while protein extracts from the same samples were analyzed by Western blotting or enzyme-linked immunosorbent assay (ELISA). RESULTS: mRNA expression levels of VEGF and HIF-1 were significantly higher in wounded fibroblasts treated with either adenosine or NO, but the highest levels occurred when treated with the combination of both. Exposure of wounded fibroblasts to this combination resulted in increased phosphorylation of p38 mitogen-activated protein kinase. CONCLUSIONS: Since VEGF and HIF-1 promote tissue adaptation and angiogenesis, high levels of adenosine and NO, localized around damaged tissue, may be beneficial for wound healing. The alpha subunit of hemoglobin potentiates fibrinolysis Alexander Morton Colorado, Ernest E Moore, MD, FACS, Hunter B Moore, MD, Christopher C Silliman, MD, PhD, Eduardo Gonzalez, MD, Anirban Banerjee, PhD University of Colorado, Aurora, CO INTRODUCTION: Systemic hyperfibrinolysis is an important component of trauma induced coagulopathy (TIC). Proteomic analysis of plasma from patients experiencing TIC has shown an elevation in hemolysis products, including hemoglobin and its
RESULTS: Fibrinolysis was enhanced in the alpha group in a concentration-dependent fashion (p¼0.0333). Median LY30 were 36% (control), 55% (200 nM), 57% (500 nM), and 64% (800nM). Fibrinolysis was unchanged by the addition of beta subunit (p¼0.9286). Median LY30 were 30% (baseline), 34% (200 nM), and 37% (500nM). At the 500 nM dose, LY30 was statistically elevated in the alpha group compared to beta group (57% vs 37%; p¼0.0125). HbA did not change fibrinolysis, even at 10-fold and 100-fold higher concentrations (p¼0.4798). Median LY30 were 25% (baseline), 17% (1.25 mM), 17% (2.5 mM), 18% (5 mM), 19% (10 mM), and 20% (20 mM). CONCLUSIONS: Fibrinolysis is enhanced in a concentrationdependent fashion by the alpha globin subunit, but not by the beta globin subunit, or HbA. These data, coupled with our findings of increased free HbA and subunit concentrations in TIC suggest alpha globin chain as a potential mediator likely involving the plasmin system. The impact of temporal, environmental, and sociocultural factors on blunt and penetrating trauma admission volumes: review of 41,613 patient admissions Vincent Cheng, Regan J Berg, MD, Dimitra Skiada, MD, Obi T Okoye, MD, Robert G Fovell, PhD, Pedro G Teixeira, MD, Demetrios Demetriades, MD, PhD, Kenji Inaba, MD, FACS Los Angeles County University of Southern California, Los Angeles, CA INTRODUCTION: The ability to predict periods of significantly increased demand for trauma care has important implications for healthcare resource planning and patient safety. Previous attempts to delineate factors associated with increased admission volumes have suffered from methodological limitations, including the frequent assessment of blunt and penetrating trauma together, neglecting these mechanisms’ different behavioral correlates. METHODS: All trauma admissions between January 1, 2006 and December 31, 2013 were reviewed and categorized by mechanism, the presence of severe injury (ISS >15), and operative need. Poisson regression evaluated trauma volume incidence rate ratios as a function of temporal, environmental, and sociocultural (holidays, celebrations and sporting events) factors.