Research - Department of Anesthesiology
Recent Grant Awards
| Research |
Recent Grant Awards [2008] [2009]
The following departmental faculty were awarded competitive and non-competitive research grants during calendar year 2009.
Luke James, MD, Assistant Professor in the Division of Otolaryngology, Head, Neck/Neuroanesthesiology was awarded a twoyear $175,000 Mentored Research Training Grant - Basic Science (MRTG-BS) from the Foundation for Anesthesia Education & Research (FAER) entitled “Pharmacogenomic Influences of ApoE and Mimetic Peptides on Neurological Outcomes as a Paradigm for Targeted Therapeutic Development in a Murine Model of Intracerebral Hemorrhage.” Intracerebral hemorrhage (ICH) is the second most common and, arguably, the most devastating form of cerebrovascular disease in patients cared for by neuro-anesthesiologists. Currently, there are limited therapeutic interventions available to these patients and essentially no pharmacological treatment for the secondary inflammation caused by the presence of brain hemorrhage. The PI and team have developed a murine model of ICH induced by stereotactic clostridial collagenase injection that mimics the human condition of microvascular breakdown and arteriolar rupture. The team proposes to utilize this model in a transgenic murine system to provide a means by which rational targeted pharmacogenomic therapy may be evaluated.Qing Ma, MD, Research Scientist in the Division of Basic Sciences and member of the Cardiopulmonary Bypass Research Laboratory was awarded a two-year $80,000 Society of Cardiovascular Anesthesiologists (SCA) Mid-Career Grant entitled “PPAR gamma as a Novel Therapeutic Target in Perioperative Cerebral Injury Following Deep Hypothermic Circulatory Arrest”. Major cardiovascular surgery employing cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) represents a unique biologic stimulus leading to profound perturbations in inflammatory, haemostatic, and oxidative stress pathways, all implicated in the pathophysiology of perioperative cerebral injury (PCI). Perioperative cerebral injury after major cardiovascular surgery is associated with significant adverse cerebral outcomes. Despite advances in surgical, anesthetic, and neuroprotective strategies, the incidence of perioperative stroke and cognitive dysfunction after cardiovascular surgery remains significant. The overall objective of this proposal is to test the hypothesis that PPARγ agonist prevents and reduces perioperative cerebral injury following surgical ischemia/reperfusion through a PPARγ and NF-κB mediated deregulation of the cerebral inflammatory response. Dr. Ma will work closely with Dr. Burkhard Mackensen as her scientific mentor and Dr. Zhiquan Zhang as collaborator for the proposal. The Chair of the SCA Research Committee stated “…SCA Committee Members uniformly found this to be the highest quality Mid-Career Grant that we reviewed this year.”
David S. Warner, MD, Chief of the Division of Basic Sciences and member of the Division of Otolaryngology, Head, Neck/Neuroanesthesiology, received a 2-year $429,000 NIH Exploratory/Development Research Grant (R21) from the National Institute of Neurological Disorders and Stroke entitled “S-Nitrosylated Hemoglobin and Ischemic Brain Injury”. Ischemic stroke is caused by cerebral blood flow (CBF) inadequate to allow brain tissue survival. It is known from humans treated with tissue plasminogen activator that ischemic tissue can be salvaged from infarction by thrombolytic CBF restoration – this improves outcome. Thus, improved CBF is a therapeutic target. The goal of this project is to determine the effectiveness of an inhaled gas, ethyl nitrite, in improving blood flow during an experimental stroke in rats. The investigative team has evidence that indicates that ethyl nitrite will selectively improve blood flow to the part of the brain that is experiencing a stroke, but that will do so with little or no effect on blood flow to other parts of the body. The team will then examine whether this effect is important in reducing the amount of tissue damage and neurologic impairment caused by the stroke.
Luke James, MD, Assistant Professor in the Division of Otolaryngology, Head, Neck/Neuroanesthesiology was awarded a four-year $308,000 Scientist Development Grant from the American Heart Association (AHA) entitled “Microglial-mediated Inflammation in a Murine Model of Intracerebral Hemorrhage as a Paradigm for Targeted Pharmacogenomic Intervention.” Intracerebral hemorrhage (ICH) is the second most common and, arguably, the most devastating form of cerebrovascular disease; however, primary parenchymal ICH is vastly understudied and, despite overall improvement in critical care, is generally associated with poor clinical outcome. Currently, there are limited therapeutic interventions available to patients with ICH and essentially
no pharmacological treatment for the secondary inflammation caused by the presence of endothelial rupture and hematoma formation. Dr. James has developed and validated a murine model of ICH induced by stereotactic clostridial collagenase injection that mimics the human condition of cerebral microvascular breakdown and arteriolar rupture. His research team proposes to utilize this model in a transgenic murine system to provide a means by which rationally derived, targeted pharmacogenomic therapy may be evaluated.
The Durham VA Patient Safety Center of Inquiry (PSCI) successfully renewed their grant from the VA National Center for Patient Safety, with funding through October 1, 2011. The $600,000 grant will support their new project, “Designing a Safer OR to ICU Patient Handover.” The PSCI is led by our VA anesthesiologists Jonathan Mark, Becky Schroeder, and Atilio Barbeito and members of the Duke Human Simulation and Patient Safety Center, Jeff Taekman, Melanie Wright, and Noa Segall. The growing multidisciplinary research group includes a cardiothoracic surgeon (Zane Atkins), VA informatics consultant (Sally Kellum), quality improvement nurse (Dawn Rogers), consultants from the Duke Fuqua School of Business Center for Leadership and Ethics (Sim Sitkin, James Emery), and technical support staff (Gene Hobbs, Becky Perfect).
W. Dan Tracey, PhD, Assistant Professor, Division of Basic Sciences and Director of the Molecular Genetics of Pain Signaling Laboratory received a 2-year $429,000 NIH Exploratory/Development Research Grant (R21) from the National Institute on Deafness and Other Communication Disorders entitled “Genome-Wide Analysis of Ion Channels Required for Mechanosensation”. A large body of evidence suggests that ion channels act as force sensors in mechanotransduction systems. In flies, the No mechanoreceptor potential-C (Nomp-C) channel has been suggested to be a force transduction channel in neurons that detect bristle deflection. In C. elegans, mechanotransduction channels of the Deg/ENaC family have been unambiguously identified as force sensors in touch neurons. The Mec10/Mec4 channel is the central component of a transduction complex that also involves extracellular matrix proteins. In bacteria, a simpler form of mechanotransduction involves a mechanosensitive channel of large conductance (MscL) and another of smaller conductance (MscS). These bacterial force-sensing channels detect membrane stretch triggered by osmotic pressure and protect the cell from rupture by allowing emergency ejection of osmolytes. Despite progress in identifying these important channels, the identities of mechanotransduction channels in vertebrate neurons remain elusive. For example, orthologs of Nomp-C and Msc channels have not been found in mammals and there is limited evidence supporting a role for Deg/ENaC’s in mammalian mechanotransduction. Since it is likely that molecular mechanisms of mechanotransduction are ancient, and evolutionarily conserved, we hypothesize that additional mechanotransduction channels have yet to be identified. The goal of this proposal is to identify candidates for these evolutionarily conserved mechanotransduction channels. Identifying the novel mechanotransduction channels and their vertebrate homologues may lead to an increased understanding of human diseases ranging from deafness to pain.
Joseph P. Mathew, MD, MHSc, Professor of Anesthesiology and Chief of the Division of Cardiothoracic Anesthesia and Critical Care Medicine received a 5-year $1,823,854 NIH Research Project Grant (R01) from the National Heart, Lung, & Blood Institute (NHLBI) entitled “Lidocaine for Neuroprotection During Cardiac Surgery”. The purpose of the study is to determine the effect of lidocaine infusion upon 1) neurocognitive function after cardiac surgery and 2) the inflammatory response across the cerebral vasculature.
David S. Warner, MD, Professor of Anesthesiology, Chief of the Division of Basic Sciences, and Director of the Multidisciplinary Neuroprotection Laboratories received a Sponsored Research Agreement ($467,686) from Angion Biomedical Corporation, as part of a NIH SBIR application entitled “Novel Neuroprotective/Restorative Therapy for Ischemic Stroke”. Dr. Warner and his laboratory are collaborating with Angion to rigorously evaluate the neuroprotective properties of refanalin, an hepatocyte growth factor mimetic in a rat model of ischemic stroke. The Duke limb of the study will focus on study of dose-dependent physiologic responses to refanalin in rats during the acute recovery phase from middle cerebral artery occlusion, define the effects of gender on the neuroprotective efficacy of refanalin, and perform long-term outcome analysis of effects of refanalin on neurocognitive, neurologic, and neurohistologic responses to standardized focal ischemic insults.
Richard Moon, MD, Medical Director of the Center for Hyperbaric Medicine and Environmental Physiology received a three-year $961,613 grant from Naval Sea Systems Command entitled “Screening Tests for Susceptibility to Immersion Pulmonary Edema (IPE)”. Swimming- induced pulmonary edema (SIPE) is a condition that occurs in divers and surface swimmers, often in young, healthy naval recruits, including combat swimmers. The condition usually resolves spontaneously or with ß2 adrenergic agonist or diuretic therapy, but it has been fatal in the military population. Risk factors include cold water, exaggerated vasoconstrictive effect of cold, exertion, fluid loading and low vital capacity. It is believed that certain individuals are more susceptible than others. This study will test the hypotheses that (a) susceptible individuals have an exaggerated increase in pulmonary artery pressure in response to cold water exercise and (b) susceptibility to SIPE is associated with certain genetic polymorphisms related to venodilatation. It is the aim of this study to identify specific genotype(s) and develop a physiological test (change in venous compliance in response to cold water immersion) that can be used to predict the risk of immersion pulmonary edema. A cohort of around 200 normal volunteers would be studied while exercising in water for 30-40 minutes. Lung water will be measured using a previously developed triple gas technique, which will be validated in a smaller number of subjects using lung MRI. The effects of oral fluid loading will also be tested.
Dr. Ashraf Habib of the Women’s Anesthesia and Critical Care Medicine Division received a two year $100,000 Covidien Research Award from the Anesthesia Patient Safety Foundation (APSF) entitled “Computerized Surveillance of Opioid Related Adverse Drug Events in the Perioperative Period”. Opioids remain the mainstay of pain relief after surgery. However their use can be associated with increased sedation, slowing of breathing, and might lead to harm and even death. This project aims to identify risk factors for the occurrence of such adverse events and implement strategies to reduce their occurrence.
David S. Warner, MD, Chief of the Division of Basic Sciences and member of the Division of Otolaryngology, Head, Neck/Neuroanesthesiology, received a 2-year $429,000 NIH Exploratory/Development Research Grant (R21) from the National Institute of Neurological Disorders and Stroke entitled “S-Nitrosylated Hemoglobin and Ischemic Brain Injury”. Ischemic stroke is caused by cerebral blood flow (CBF) inadequate to allow brain tissue survival. It is known from humans treated with tissue plasminogen activator that ischemic tissue can be salvaged from infarction by thrombolytic CBF restoration – this improves outcome. Thus, improved CBF is a therapeutic target. The goal of this project is to determine the effectiveness of an inhaled gas, ethyl nitrite, in improving blood flow during an experimental stroke in rats. The investigative team has evidence that indicates that ethyl nitrite will selectively improve blood flow to the part of the brain that is experiencing a stroke, but that will do so with little or no effect on blood flow to other parts of the body. The team will then examine whether this effect is important in reducing the amount of tissue damage and neurologic impairment caused by the stroke.
Luke James, MD, Assistant Professor in the Division of Otolaryngology, Head, Neck/Neuroanesthesiology was awarded a four-year $308,000 Scientist Development Grant from the American Heart Association (AHA) entitled “Microglial-mediated Inflammation in a Murine Model of Intracerebral Hemorrhage as a Paradigm for Targeted Pharmacogenomic Intervention.” Intracerebral hemorrhage (ICH) is the second most common and, arguably, the most devastating form of cerebrovascular disease; however, primary parenchymal ICH is vastly understudied and, despite overall improvement in critical care, is generally associated with poor clinical outcome. Currently, there are limited therapeutic interventions available to patients with ICH and essentially
no pharmacological treatment for the secondary inflammation caused by the presence of endothelial rupture and hematoma formation. Dr. James has developed and validated a murine model of ICH induced by stereotactic clostridial collagenase injection that mimics the human condition of cerebral microvascular breakdown and arteriolar rupture. His research team proposes to utilize this model in a transgenic murine system to provide a means by which rationally derived, targeted pharmacogenomic therapy may be evaluated.
The Durham VA Patient Safety Center of Inquiry (PSCI) successfully renewed their grant from the VA National Center for Patient Safety, with funding through October 1, 2011. The $600,000 grant will support their new project, “Designing a Safer OR to ICU Patient Handover.” The PSCI is led by our VA anesthesiologists Jonathan Mark, Becky Schroeder, and Atilio Barbeito and members of the Duke Human Simulation and Patient Safety Center, Jeff Taekman, Melanie Wright, and Noa Segall. The growing multidisciplinary research group includes a cardiothoracic surgeon (Zane Atkins), VA informatics consultant (Sally Kellum), quality improvement nurse (Dawn Rogers), consultants from the Duke Fuqua School of Business Center for Leadership and Ethics (Sim Sitkin, James Emery), and technical support staff (Gene Hobbs, Becky Perfect).
W. Dan Tracey, PhD, Assistant Professor, Division of Basic Sciences and Director of the Molecular Genetics of Pain Signaling Laboratory received a 2-year $429,000 NIH Exploratory/Development Research Grant (R21) from the National Institute on Deafness and Other Communication Disorders entitled “Genome-Wide Analysis of Ion Channels Required for Mechanosensation”. A large body of evidence suggests that ion channels act as force sensors in mechanotransduction systems. In flies, the No mechanoreceptor potential-C (Nomp-C) channel has been suggested to be a force transduction channel in neurons that detect bristle deflection. In C. elegans, mechanotransduction channels of the Deg/ENaC family have been unambiguously identified as force sensors in touch neurons. The Mec10/Mec4 channel is the central component of a transduction complex that also involves extracellular matrix proteins. In bacteria, a simpler form of mechanotransduction involves a mechanosensitive channel of large conductance (MscL) and another of smaller conductance (MscS). These bacterial force-sensing channels detect membrane stretch triggered by osmotic pressure and protect the cell from rupture by allowing emergency ejection of osmolytes. Despite progress in identifying these important channels, the identities of mechanotransduction channels in vertebrate neurons remain elusive. For example, orthologs of Nomp-C and Msc channels have not been found in mammals and there is limited evidence supporting a role for Deg/ENaC’s in mammalian mechanotransduction. Since it is likely that molecular mechanisms of mechanotransduction are ancient, and evolutionarily conserved, we hypothesize that additional mechanotransduction channels have yet to be identified. The goal of this proposal is to identify candidates for these evolutionarily conserved mechanotransduction channels. Identifying the novel mechanotransduction channels and their vertebrate homologues may lead to an increased understanding of human diseases ranging from deafness to pain.
Joseph P. Mathew, MD, MHSc, Professor of Anesthesiology and Chief of the Division of Cardiothoracic Anesthesia and Critical Care Medicine received a 5-year $1,823,854 NIH Research Project Grant (R01) from the National Heart, Lung, & Blood Institute (NHLBI) entitled “Lidocaine for Neuroprotection During Cardiac Surgery”. The purpose of the study is to determine the effect of lidocaine infusion upon 1) neurocognitive function after cardiac surgery and 2) the inflammatory response across the cerebral vasculature.
David S. Warner, MD, Professor of Anesthesiology, Chief of the Division of Basic Sciences, and Director of the Multidisciplinary Neuroprotection Laboratories received a Sponsored Research Agreement ($467,686) from Angion Biomedical Corporation, as part of a NIH SBIR application entitled “Novel Neuroprotective/Restorative Therapy for Ischemic Stroke”. Dr. Warner and his laboratory are collaborating with Angion to rigorously evaluate the neuroprotective properties of refanalin, an hepatocyte growth factor mimetic in a rat model of ischemic stroke. The Duke limb of the study will focus on study of dose-dependent physiologic responses to refanalin in rats during the acute recovery phase from middle cerebral artery occlusion, define the effects of gender on the neuroprotective efficacy of refanalin, and perform long-term outcome analysis of effects of refanalin on neurocognitive, neurologic, and neurohistologic responses to standardized focal ischemic insults.
Richard Moon, MD, Medical Director of the Center for Hyperbaric Medicine and Environmental Physiology received a three-year $961,613 grant from Naval Sea Systems Command entitled “Screening Tests for Susceptibility to Immersion Pulmonary Edema (IPE)”. Swimming- induced pulmonary edema (SIPE) is a condition that occurs in divers and surface swimmers, often in young, healthy naval recruits, including combat swimmers. The condition usually resolves spontaneously or with ß2 adrenergic agonist or diuretic therapy, but it has been fatal in the military population. Risk factors include cold water, exaggerated vasoconstrictive effect of cold, exertion, fluid loading and low vital capacity. It is believed that certain individuals are more susceptible than others. This study will test the hypotheses that (a) susceptible individuals have an exaggerated increase in pulmonary artery pressure in response to cold water exercise and (b) susceptibility to SIPE is associated with certain genetic polymorphisms related to venodilatation. It is the aim of this study to identify specific genotype(s) and develop a physiological test (change in venous compliance in response to cold water immersion) that can be used to predict the risk of immersion pulmonary edema. A cohort of around 200 normal volunteers would be studied while exercising in water for 30-40 minutes. Lung water will be measured using a previously developed triple gas technique, which will be validated in a smaller number of subjects using lung MRI. The effects of oral fluid loading will also be tested.
Dr. Ashraf Habib of the Women’s Anesthesia and Critical Care Medicine Division received a two year $100,000 Covidien Research Award from the Anesthesia Patient Safety Foundation (APSF) entitled “Computerized Surveillance of Opioid Related Adverse Drug Events in the Perioperative Period”. Opioids remain the mainstay of pain relief after surgery. However their use can be associated with increased sedation, slowing of breathing, and might lead to harm and even death. This project aims to identify risk factors for the occurrence of such adverse events and implement strategies to reduce their occurrence.
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