Ronald L. Harter, MD, Chair
Anesthesiology has nearly 50 faculty members with basic and patient-oriented research interests. Investigators use animal or genomic models to study mechanisms of hypertension, chronic heart failure, ischemic spinal cord injury (ISCI), inflammatory bowel diseases (IBD), cell signaling and neural circuit pathways, constipation and neurogenic diarrhea. They also do clinical studies on perioperative monitoring devices, IBD, wound healing, kidney protection during surgery, ISCI, fMRI brain imaging of pain and anesthesia, intraocular pressure and 3-D echocardiography. The department has 13 principal investigators, 8 co-investigators, 22 research personnel and many medical students and residents engaged in research – a level of involvement that has increased peer-reviewed publications, research funding and grant submissions. In 2008, the department received nearly $1 million for 9 new multicenter clinical trials, and investigators submitted grant applications for $6.5 million to outside agencies. The department seeks to increase funded research space, build a clinical research processing lab, recruit additional NIH researchers, establish interdisciplinary collaborations, link junior researchers with established investigators, and develop a clinical research office and conference area for its anesthesia research team.
Ongoing Research Programs
- Enteric Neurosciences, Neural Circuits and Neurogastroenterology – Studies supported by the National Institutes of Health, Diabetes & Digestive & Kidney Diseases (NIDDK; PI, Fievos Christofi, PhD) are investigating the function, neuroimmune communication and neuroplasticity of the enteric nervous system, or “little brain in the gut,” that coordinates all gut functions, motility, secretion, luminal transport and vasomotor activity of the gastrointestinal tract. Its behavior is altered by inflammatory bowel diseases (e.g., IBD or IBS) associated with various gastrointestinal symptoms (constipation or diarrhea, dysmotility and irritable bowel, and, in advanced IBD, severe malabsorption, malnutrition, obstruction and pain sensation that may require surgery). Christofi’s research is focused on purinergic neural circuits and enteric reflexes in normal and inflamed gut in human and animal models in collaboration with Bradley Needleman, MD; Jacqueline Wunderlich, MD; PhD; Iveta Grants, BSc; Tianhua Ren, MD, PhD; and Hamdy Hassanain, PhD.
- Neural Mechanisms of Opioids, Immune Mediators, Anesthetics and Surgery on Bowel Dysfunction – Yun Xia, MD, PhD, is submitting his first R01 application as a new investigator who received a five-year NIDDK KO8 Clinical Investigator Award to study glia and the enteric nervous system. His studies are focused on receptors and mechanisms involved in gut neural circuits. His other basic research studies are elucidating mechanisms of mast-cell mediators on the enteric nervous system, as well as opioids and anesthetics on GI function, and he is involved in multicenter clinical trials funded by the pharmaceutical industry on postoperative ileus and opioid bowel induced dysfunction.
- Hamdy Hassanain, PhD, has a growing research program on molecular mechanisms and signaling pathways involved in cardiovascular diseases; he has developed various genomic models of cardiovascular diseases and collaborates with researchers at Ohio State and elsewhere on extramurally funded projects, including NIH. Hassanain has 5 PhD students with fellowships in his laboratory representing the channel foreign student exchange program between: Egypt and American Universities; Molecular, Cellular and Developmental Biology; and the Ohio State Biochemistry and Biophysics program.
- Hamdy Elsayed-Awad, MD, is a lead investigator in clinical studies targeting the effects of robotic surgery on intraocular pressure, ischemic spinal cord injury after surgery to repair a thoracoabdominal aortic aneurysm, and the effects of local anesthetics on wound healing after cardiac surgery.
- Brain imaging in response to pain or anesthesia – The department is developing expertise in state-of-the-art imaging techniques for clinical (brain imaging) and cellular (neural networks) studies. Robert Small, MD, and Keith Vogt are applying functional magnetic resonance imaging to study physiological noise reduction in humans and effect of pain or anesthetics.
- Heart failure – Mark Gerhardt, MD, PhD, is the lead investigator in studies exploring the molecular mechanisms of ventricular remodeling in large animal models of heart failure and congenital heart disease.
- 3-D echocardiography and finite element analysis – Nadia Nathan, MD, in collaboration with industry and foreign researchers from Germany, is developing a system for fully automated import of cardiac data (e.g., pressure, elasticity, geometry components, hemodynamic parameters) to a finite element-modeling tool (Abaqus) that incorporates 3-D echocardiography geometry data and provides cardiac data quantification that has the potential for use in managing cardiac interventions. Individual simulation of interventions may be suitable for surgical planning, training and education.
- Sergio Bergese, MD, is the Department’s lead investigator on multicenter clinical trials funded by various pharmaceutical companies in neuroanesthesia, monitoring devices for neurosurgery, postoperative nausea and vomiting prophylaxis in neurosurgery, postoperative ileus, postoperative pain management, low-dose dexmeditomitine for sedation, use of absorbable antibiotic sponges to reduce surgical wound infection post-surgery, and intraoperative somatosensory-evoked potentials.
Research Accomplishments of 2008
- A study presented in Copenhagen, Denmark, by Fievos Christofi, PhD, was the first to show that the endogenous purines adenosine and ATP play an important role in neurotransmission in the human enteric nervous system. Collaborators included Jacqueline Wunderlich, MD, PhD; Tianhua Ren, MD, PhD; Scott Melvin, MD; and Bradley Needleman, MD.
- Fievos Christofi, PhD, and a team of investigators (including Leszek Rybaczyk, PhD; Andrew Rozmiarek, MD; Kristen Circle, MSc; Iveta Grants, BSc; Bradley Needleman, MD; Jacqueline Wunderlich, MD, PhD; and Kun Huang, PhD) published an article in the journal Inflammatory Bowel Diseases titled “A New Bioinformatics Approach to Analyze Gene Expressions and Signaling Pathways Reveals Unique Purine Gene Dysregulation Profiles that Distinguish between CD and UC.” This finding may be important for diagnostics to distinguish between CD and UC with further confirmation. Christofi, a leading investigator in an emerging program on neuroplasticity in the enteric nervous system in inflammatory bowel diseases, has discovered that mice with functional knockout of the adenosine A3 receptor are protected from developing dextran-sodium sulfate-induced colitis.
- Yun Xia, MD, PhD, is submitting a grant application to the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) to study the neurobiology of paracrine/immune mediator release from mast cells on the enteric nervous system (ENS). This is important since emerging research concepts indicate that mast cells are significant contributors to the pathogenesis of IBD and IBS. Proposed studies will use an integrated approach to examine immune-neural communication at the cellular and molecular levels of organization to clarify the neurobiology of platelet activating factor in the ENS.
Emerging programs on patient-oriented research with NIH funding potential include:
- Heart failure – Mark Gerhardt, MD, PhD, who is studying heart failure in large-animal models, published in the journal Life Sciences (in collaboration with The Heart Center and Center for Cardiopulmonary Medicine at Nationwide Children’s Hospital) findings that demonstrate upregulation of the cytoskeletal protein desmin is a robust marker of heart failure severity. Mark Gerhardt is the recipient of a prestigious mid-career develoment award from the Society of Cardiac Anesthesia, and a grant from the Heart Center Translational Research Institute at Nationwide Children's Hospital with Loren Wold, PhD, Alistair Phillips, MD, and James Steward, PhD.
- Intraocular pressure – Hamdy Elsayed-Awad, MD, is on an interdisciplinary team studying the effect of robotic surgery on intraocular pressure. Ohio State’s Medical Center has pioneered the use of robotic surgery in urology, gynecology and cardiac surgery, but this technology can create problems for anesthesiologists such as an increase in intraocular pressure during prostatectomy and hysterectomy due to steep Trendelenburg position. The Ohio State team was the first to recognize and study this problem under the leadership of Paul Weber, MD, and Thomas Mauger, MD – work that resulted in a publication in the journal Anesthesia & Analgesia.
- Ischemic spinal cord injury (ISCI) – ISCI after aortic surgery can be a devastating complication in patients with thoracoabdominal aortic aneurysms (TAAA) that can lead to paraplegia. Hamdy Elsayed-Awad, MD, and an interdisciplinary team developed a canine model to study ISCI, which has been published in the journal Experimental Neurology with Michael Oglesbee, DVM, PhD, Fievos Christofi, PhD, and Daniel Smeak, MD. Awad is developing and characterizing a mouse model to study this problem and the underlying cellular and molecular mechanisms of ISCI after surgery to repair a TAAA in collaboration with Phil Popovich, PhD.
- The Effect of Local Anesthetics on Wound Healing After Cardiac Surgery – The use of local anesthetics to alleviate pain after cardiac surgery is important, but the effect of local anesthetics on wound healing has not been studied in vivo in humans. Hamdy Elsayed-Awad, MD has teamed up with Chandan Sen, PhD and Sashwati Roy, PhD to study this process to enhance pain relief, improve wound recovery and prevent wound-healing dysfunction.
- Genomic Models of Disease – The rac-1 CA transgenic model developed by Hamdy Hassanain, PhD, led to a potential discovery for treatment of Kaposi sarcoma, a tumor caused by HHV8 that is known as one of the AIDS-defining illnesses. Hassanain is a co-investigator on a pending patent with Pascal Goldschmidt, MD, of the University of Miami Health System, and others.
- 3-D Echocardiography – Nadia Nathan, MD, is lead investigator on a study published in the European Journal of Echocardiography on “Mechanisms of Valve Competency After Mitral Valve Annuloplasty for Ischaemic Mitral Valve Regurgitation Using the Geoform Ring Using 3-D Echocardiography.”
- Functional MRI Brain Imaging – Robert Small, MD, and Keith Vogt, an MD/PhD candidate, in collaboration with Jim Ibinson, PhD; Douglas Gould, PhD; and Petra Schmalbrock, PhD, are using functional magnetic resonance imaging (fMRI) to study physiological noise correction in fMRI signal processing and imaging of the brain in response to pain and anesthesia. They presented one study, which examined the effects of respiratory volume and rate changes on the acquired fFMRI signal, at the Proceedings of the International Society of Magnetic Resonance Medicine. The other project examines pain processing in healthy adults to determine differences between dominant vs. non-dominant hand stimulation, and differences between right- and left-handed people (published as an abstract in the journal Anesthesiology).
- Intra-operative monitoring devices – Roger Dzwonczyk, MSc, PE, is a co-investigator on various clinical trials and has a longstanding interest in studies with intraoperative monitoring devices. He co-authored two publications in 2008: “Electrotonic Remodeling Following Myocardial Infarction in Dogs Susceptible and Resistant to Sudden Cardiac Death” in the Journal of Applied Physiology, and “Electrical Noise in the Intraoperative Magnetic Resonance Imaging Setting” in the journal Anesthesia & Analgesia.
- Erika Puente, MD, is a research scientist and member of the clinical trials/research investigative team of Sergio Bergese, MD. Her emerging clinical research studies as principal investigator are on postoperative nausea and vomiting, management of postoperative pain in several patient populations, and neuropathic pain. Her other research activities include brain monitoring and intraoperative monitoring of somatosensory-evoked potentials, and she is sub-investigator on a number of funded multicenter clinical trials with Bergese.
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