Dr. Moon Awarded $2M for Diving Studies

Richard E. Moon, MD, CM, MSc, FRCP, FACP, FCCPDuke Anesthesiology’s Richard Moon, MD, CM, MSc, FRCP(C), FACP, FCCP, has been awarded more than $2 million in funding for diving studies from branches of the United States Navy.

The Office of Naval Research has awarded Moon a three-year, $1,209,589 grant for his project, “Integrated Diaphragmatic Function, Chemosensitivity, Erythrocyte Gas Transport and Endurance in Exercising Divers.”

Moon’s study will determine (1) the effectiveness of breathing carbon monoxide on diaphragm training (his research team has previously shown that low dose carbon monoxide upregulates mitochondrial biogenesis in humans); (2) whether carbon monoxide-enhanced diaphragm training increases endurance in divers during underwater exercise; (3) the degree to which oxygen and carbon dioxide exchange is determined by gas channels in human red blood cells.

Additionally, the Naval Sea Systems Command (NAVSEA) has awarded Moon, medical director of Duke’s Center for Hyperbaric Medicine & Environmental Physiology, an $850,502 contract for his project, “Perfluoromethane to Reduce Decompression Sickness after Heliox Dives.” This contract will fund studies in pigs to determine whether perfluoromethane breathing during decompression from a dive reduces decompression sickness.

Stacey HiltonDr. Moon Awarded $2M for Diving Studies
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Dr. Gasier Awarded Naval Research Grant

Heath Gasier, PhDThe Office of Naval Research has awarded Duke Anesthesiology’s Heath Gasier, PhD, a $227,954 grant to study the effects of hyperbaric oxygen on skeletal muscle calcium regulation and mitochondrial function.

Oxidant production increases with strenuous muscle contractions and has been reported to cause or contribute to fatigue. It is, therefore, probable that intramuscular oxidant production is increased during prolonged and repeated HBO2 exposures and results in damage to organelles and regulatory proteins involved in muscle contraction and bioenergetics.

This research will help Gasier determine the impact of skeletal muscle oxidant production on calcium regulation and mitochondrial function in mice exposed to HBO2, ultimately identifying new approaches for preventing oxygen toxicity and optimizing performance in divers.

In this study, he will implement an innovative combination of biological techniques. His approach allows for real time measurement of total and mitochondrial superoxide and calcium levels, and mitochondrial membrane potential in live muscle fibers ex vivo. Combined with immunoblotting and immunofluorescence, he aims to identify the potential source of muscle fatigue. Gasier’s central hypothesis is that prolonged and repeated HBO2 exposures increase oxidation of RyR1 and STIM1 that increases intracellular and mitochondrial calcium uptake, resulting in impaired mitochondrial function. This hypothesis is based on the synthesis of work by others.

Gasier’s work is expected to discover whether critical targets involved in muscle contraction are influenced by HBO2. Results of this research will have an important and positive impact because they will offer a strong scientific framework for testing specific drugs or antioxidants on muscle and aerobic exercise performance after HBO2.

Stacey HiltonDr. Gasier Awarded Naval Research Grant
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Dr. Nicoara Awarded Mid-Career Grant

Alina Nicoara, MD, FASEThe Society of Cardiovascular Anesthesiologists (SCA) has awarded Duke Anesthesiology’s Alina Nicoara, MD, FASE, a two-year, $100,000 SCA 2021 Mid-Career Grant for her project, titled “Right Ventricle Adaptive Changes in Patients Undergoing Left Ventricular Assist Device Implantation.”

According to Nicoara, while left ventricular assist device (LVAD) technology has advanced remarkably, ongoing lack of reliable predictors of right heart failure (RHF) significantly hinders care optimization. Through her work using 3D echocardiography, she expects to provide novel insights into right ventricle functional adaptations after LVAD implantation, advance the ability to identify patients at risk for developing RHF after LVAD implantation, and add to the work done by other investigators at Duke.

“As with everything else, this could not have been accomplished without the help of a village; encouragement from Drs. Joseph Mathew, Mihai Podgoreanu and Carmelo Milano, critical but friendly eyes from Drs. Anne Cherry and Jorn Karhausen, patience from Christopher Allen and Bonita Funk, and help throughout the years from mentors Drs. Madhav Swaminathan and Mark Stafford-Smith,” says Nicoara, associate professor of anesthesiology. “I would also like to thank all of our adult cardiothoracic anesthesiology and critical care medicine fellows. Although by the time they arrive at Duke, most projects have been fleshed out, they instill vital energy and enthusiasm into driving these projects to completion.”

Nicoara received the award virtually at the SCA’s 43rd Annual Meeting and Workshops on April 26.

Stacey HiltonDr. Nicoara Awarded Mid-Career Grant
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Dr. Terrando to Study the Role of the Blood-Brain Barrier

Niccolò Terrando, BSc (hons), DIC, PhDReservoir Neuroscience, Inc, has awarded Duke Anesthesiology’s Niccolò Terrando, PhD, an $80,143 grant to study Therapies to Protect the Blood-Brain Barrier After Surgery.” The project will evaluate the efficacy of Reservoir’s experimental compounds to protect the blood-brain barrier and prevent cognitive deficits and delirium-like behavior following orthopedic surgery. Designed as a pre-clinical academic-industry collaboration, this study has the potential to advance novel, first-in-kind treatments to improve debilitating patient outcomes in postoperative neurocognitive disorders (PND) – an unmet disease area.

Surgeries, including cardiac and orthopedic, often cause neurological complications, such as post-operative delirium and cognitive decline. These outcomes can be severely debilitating and in older adults, can create risk for onset of chronic dementia. It is not yet known how delirium and PNDs develop, or how to effectively treat this complication.

The Neuroinflammation and Cognitive Outcomes Laboratory at Duke Anesthesiology, directed by Terrando, has developed models to study the pathogenesis of postoperative delirium and strategies to combat it. In particular, the investigators have focused on the role for surgery-induced systemic inflammation in causing breakdown of the blood-brain barrier (BBB), a critical interface between the periphery and the central nervous system that regulates brain homeostasis to enable proper functioning. The BBB is often impaired in aging and neurologic disorders, such as epilepsy and Alzheimer’s disease. They have described changes in the BBB following orthopedic surgery, suggesting that opening of this barrier enables immune cells (like monocytes) and molecules (like fibrinogen) to access the brain and trigger pathological disease outcomes. This vascular pathology is especially evident in the context of neurodegeneration as they have described in a recent study published in Alzheimer’s and Dementia.

“The role of the blood-brain barrier in conditions like delirium is just starting to emerge. We are thrilled for this opportunity to work with Reservoir Neuroscience to test novel therapeutics that have the potential to heal the blood-brain barrier and hopefully prevent delirium,” says Terrando, associate professor in anesthesiology.

Reservoir Neuroscience, Inc, is developing new drugs to treat BBB dysfunction. These experiments are designed to provide proof-of-concept of a novel approach to improve outcomes in a rodent model of orthopedic surgery.

Stacey HiltonDr. Terrando to Study the Role of the Blood-Brain Barrier
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CAPER Unit Awarded Grant to Study New Lipid Formulation

Duke Anesthesiology’s Critical Care and Perioperative Population Health Research (CAPER) Unit

Duke Anesthesiology’s Paul Wischmeyer, MD, EDIC and the Critical Care and Perioperative Population Health Research (CAPER) Unit have been awarded a $130,000 grant for their project, titled “Impact of SMOFlipid on Clinical Outcomes Among Patients Receiving Parenteral Nutrition: An Interrupted Time Series Analysis.” The researchers will use the funding to study the effect of a newly-implemented advanced parenteral nutrition lipid on clinical outcomes versus previously used Omega-6 soy lipid.

The grant was awarded by Fresenius-Kabi Inc. Wischmeyer serves as the principal investigator of the grant; co-investigators include Drs. Vijay Krishnamoorthy, Karthik Raghunathan, Tetsu Ohnuma, Krista Haines (Duke Surgery), and Surgical Intensive Care Unit fellow, Dr. Osamudiamen Obanor.

The research team will examine the hypothesized benefits of a new IV nutrition lipid used for total parenteral nutrition (TPN) on clinical outcomes in Duke’s patients since Duke adopted the new lipid in 2017. Duke was among the first academic health centers in the nation to widely adopt the new lipid as it was only FDA approved in 2017. Wischmeyer notes that parenteral nutrition has been traditionally thought to potentially lead to increased infection risk. However, he says recent large randomized trials in Intensive Care Unit (ICU) patients in high-impact journals (New England Journal of Medicine, Lancet, JAMA) have shown there is no longer any association of TPN with infectious risk, even in ICU patients; but it is unclear what factors have reduced this risk.

One hypothesis the newly-funded study will explore is that newer lipid formulations containing fish oil, olive oil and a “healthier” fat mix reduces infection versus previously utilized Omega-6 lipids that have been used in the US for more than 40 years. This new trial will look at all Duke patients from neonates to adults who received new, healthier (SMOF) lipid formulation at Duke. And, using the unique talents of the CAPER Unit, they’ll compare similar patients from the period immediately prior to the new lipids introduction looking for differences in infection, length of stay, liver injury, and other clinical outcomes.

Results of this study are expected to provide unique insight to specific contribution of new, healthier lipid formulations to TPN safety and improved clinical outcomes. This could also lead to larger clinical trials or large health outcome database research funding opportunities to explore this question and other methods to improve outcomes with TPN.

“The US has a unique opportunity to finally utilize a safe and more optimally-balanced lipid formulation that has shown preliminary data to reduce infection, length of stay and improve clinical outcomes,” says Wischmeyer, professor of anesthesiology and associate vice chair for clinical research. “This study with our Duke Anesthesiology CAPER Unit provides a unique ‘real-world’ clinical care research opportunity to evaluate the contribution of this long-awaited new generation of lipid formulations to improve outcomes.”

Stacey HiltonCAPER Unit Awarded Grant to Study New Lipid Formulation
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Dr. Martucci Earns Research Incubator Award

Katherine Martucci, PhDDuke Anesthesiology’s Katherine Martucci, PhD, is among the investigators on a cross-departmental research team that has been awarded a 2020 Research Incubator Award ($75,000 grant) from the Duke Institute for Brain Sciences (DIBS) for their project titled, “Neural Mechanisms Underlying Tobacco Withdrawal-Induced Hyperalgesia.”

This award is designed to promote high-risk/high-return neuroscience research that is collaborative, crosses disciplinary boundaries, and is likely to draw external funding. The collaborative project brings together Martucci, and Duke Psychiatry & Behavioral Sciences’ Drs. Maggie Sweitzer, F. Joseph McClernon and Alison Adcock.

Chronic pain and cigarette smoking influence one another, in that smokers are more likely to have pain, and individuals with pain are more likely to smoke. People with chronic pain have more difficulty quitting smoking, in part, because temporarily going without smoking (early withdrawal) leads to increased pain sensitivity.

The goal of the study is to examine the brain’s response to heat pain stimuli among smokers in early withdrawal, to better understand the reasons for increased pain sensitivity. Daily smokers will complete two fMRI sessions, one after smoking as usual, and one after not smoking for 24 hours. During the scans, participants will experience heat pain delivered through an electrode and will provide ratings of their pain response. It is expected that participants’ ratings of pain in response to heat stimuli will be greater during the withdrawal session, and that this increased pain will be associated with greater activation throughout a network of brain regions involved in perceiving pain. This approach will allow the research team to determine which brain regions are most involved in pain sensitivity during withdrawal and which will help to identify targets for treatment. In addition, these processes might differ among smokers who also have chronic pain, compared to those who do not. As such, half of the participants will be those diagnosed with chronic pain, while the other half will be pain-free. The investigators anticipate that the effects of smoking withdrawal on pain-related brain function will be more pronounced among those with chronic pain.

Stacey HiltonDr. Martucci Earns Research Incubator Award
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