Department of Anesthesiology

Dr. Glenn P. Gravlee, Chair

Anesthesiology has 42 faculty members with basic and patient-oriented research interests aligned with the Medical Center’s Neurosciences, Heart, Imaging and Transplantation Signature Programs. Investigators use animal or genomic models to study mechanisms of ischemic spinal cord injury, neural plasticity, postoperative ileus, mechanosensitivity, inflammatory bowel diseases (IBD), irritable bowel syndrome, chronic heart failure, hypertension, wound healing, cell-signaling and obesity surgery. These efforts are complemented by clinical studies for ischemic spinal cord injury in thoracoabdominal aortic aneurysm patients, IBD, fMRI imaging of pain pathways and anesthesia, neuroanesthesia, heart failure with 3-D echocardiography and finite element analysis, cardio/bioimpedance, computer modeling, transplant survival and morbid obesity, weight loss and resolution of type 2 diabetes. Studies are funded through the National Institutes of Health (NIH), the National Heart Foundation or industry grants. The Department has 35 active and mostly investigatorinitiated clinical research studies. Its studies resulted in 15 peer-reviewed publications in 2006.

Ongoing Research Programs

Cardiovascular Diseases:
Heart failure: Mark Gerhardt, MD, PhD, is developing a program on chronic ischemic heart failure (CHF) with a focus on b-adrenergic receptor dysfunction, molecular signaling and remodeling in a microinfarction-induced ovine model of CHF with collaborations among investigators at Ohio State and Children’s Heart Institute. Studies were funded in part by a recent National Heart Foundation (NHF) grant, a Foundation of Anesthesia and Education (FAER) development grant, and an earlier American Heart Association (AHA) grant.
Hypertension and vascular remodeling: Genomic modeling is a powerful approach to studying mechanisms of disease. Hamdy Hassanain, PhD, in collaboration with Neurosciences investigators and Ohio State’s Davis Heart and Lung Research Institute, is using transgenic mouse models to study heart failure, hypertension, physiological regulation of hypertension, vascular remodeling, wound healing, receptor function or dysfunction, and diabetic vascular disease.
3-D echocardiography and finite element analysis: Nadia Nathan, MD, in collaboration with Cardiovascular Medicine, is developing a system for fully automated import of cardiac data (e.g., pressure, elasticity, geometry components) to a finite element modeling tool (Abaqus) that incorporates 3-D echocardiography geometry data and provides cardiac data quantification for potential use in managing cardiac interventions. Individual simulation of interventions may be suitable for surgical planning, training and education.
Brain and Little-Brain Imaging: Anesthesiology is developing expertise in state-of-the-art imaging techniques for clinical (whole-brain imaging) and cellular (neural networks) studies. In addition to Dr. Nathan’s 3-D echocardiography, Robert Small, MD, and interdisciplinary collaborators are applying functional magnetic resonance imaging (fMRI) to study brain activation caused by pain and in response to anesthesia. They first published this in Anesthesiology in 2004. At the cellular level, Jacqueline Wunderlich, MD, PhD, in collaboration with GI surgery (Scott Melvin, MD, Brad Needleman, MD, and Fievos Christofi, PhD), is using Ca2+ imaging to study activation and function of the “little brain in the gut,” the human enteric nervous system, in health and disease.
Ischemic Spinal Cord Injury: Hamdy Elsayed- Awad, MD, and an interdisciplinary team are developing a program in ischemic spinal cord injury for patients undergoing surgery to repair thoracoabdominal aortic aneurysms (TAAA). Spinal cord injury leading to paraplegia is a devastating complication in TAAA. Studies in human, large animal and genomic models are focused on the cellular and molecular mechanisms of ischemic spinal cord injury. The potential exists for testing new therapeutic interventions to protect the spinal cord.
Neuroanesthesia: Clinical studies by Sergio Bergese, MD, and his investigative team – including residents and medical students – involve both investigator-initiated trials and multi-center trials, such as the National Awake Intubation Trial. Studies include testing the noise in a new MEDRAD Monitor during neurosurgery, pharmacologic influence of anesthetic agents on somatosensory-evoked potential and MEPs, monitoring variations in cerebral state index, a new drug for postoperative nausea and vomiting, and clinical evaluation of a device to speed emergence from inhaled anesthesia. The latter is in collaboration with Bachar Haschwa, MD, and Roger Dzwonczyk.
Enteric Neuroscience and Neurogastroenterology: Studies supported by the National Institutes of Health, National Institute of Diabetes & Digestive & Kidney Diseases (PIs: Fievos Christofi, PhD, and Yun Xia, MD, PhD) are investigating the function, neuroimmune communication and dysfunction of the enteric nervous system or “little brain of the gut.” It regulates motility, secretion and vasomotor functions of the gut and is strongly influenced by immune/inflammatory responses. In disease, dysfunction can cause or contribute to diarrhea, constipation, dysmotility, obstruction, postoperative ileus, pain or irritable bowel syndrome. Christofi’s research is focused on: gut purinergic neural circuits and reflexes involved in the physiological regulation of motility and secretion; cell signaling and neuroplasticity in inflammatory bowel diseases, irritable bowel syndrome and post-operative ileus; molecular mechanisms of mechanosensitivity in gut sensory enterochromaffin cells; and the role of adenosine and nucleotide receptors as therapeutic targets in gut inflammatory diseases.

Research Accomplishments of 2006

New Grants: Mark Gerhardt, MD, PhD, received a grant from the National Heart Foundation on PKA-Phosphorylation of B2-Adrenergic Receptors in CHF. Fievos Christofi, PhD, received a five-year competing-renewal grant from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, on Adenosine Receptors as Therapeutic Targets in Inflammatory Bowel Diseases, He also was awarded an institutional RIF Award for related research. Sergio Bergese, MD, received industry grants for clinical studies or multicenter trials from Hospira, Baxter HealthCare Corp., Medrad Inc. A number of other grants are in preparation.
Genomic Models of Hypertension: Studies led by Hamdy Hassanain, PhD, and collaborators at Ohio State’s Davis Heart and Lung Research Institute, (directed by Jay Zweier, MD) and other institutions resulted in a publication in Antioxidant and Redox Signaling characterizing hypertension caused by transgenic overexpression of the small GTP-ase Rac 1 in a transgenic mouse model developed by Hassanain. Continuous Rac 1/NADPH oxidase activation leads to superoxide radical production and hypertension. An NIH grant is pending.
Heart Failure: Mark Gerhardt, MD, PhD, in collaboration with Gretel Monreal (PhD student), characterized the acute changes in myocardial electrolytes induced by left ventricular assist device (LVAD) support in heart failure (ASAIO J 2006 Nov 28, e-pub ahead of print). Other studies, in collaboration with John Bauer, PhD, and colleagues at the Children’s Heart Institute, are providing insight into intracellular remodeling in myocytes, b-receptor function and acute stress protein levels in an ovine model of chronic heart failure. Nadia Nathan, MD, is using finite element modeling software to quantify pre- and post-interventional cardiac reconstruction data based on modeling data sets from surgical ventricular repair therapy and cardiac resynchronization therapy. This was published in BioMedical Engineering OnLine.
Neurogastroenterology/Neuroscience: Studies in the lab of Fievos Christofi, PhD, in collaboration with investigators in Neuroscience (Helen Cooke, PhD), at Ohio State’s Davis Heart and Lung Research Institute (Arturo Cardounel, PhD) and at Lakehead University in Canada (Zacharias Suntres, PhD), showed that a drug targeting ADOA3R is a potential therapy for experimental inflammatory bowel disease. The findings were published in IBD as “Mechanistic hypotheses generated in animal IBD models are being tested first in ex vivo human surgical IBD gut neural tissues, first-time analysis of data base gene abnormalities in IBD patients.” These studies could pave the way for human clinical trials. A second study published in the Internat J Parasitology proved that hyperexcitability and neuroplasticity in gut sensory neurons are caused by amplification of the Gs/AC/cAMP/PKA/pCREB signaling pathway in gut infected with the human pathogen Trichinella spiralis. The pathway is a general target for most neuropeptide transmitters, a major gateway to gut reflexes and a potential therapeutic target in irritable bowel syndrome. Yun Xia, MD, PhD, and collaborators in the Department of Physiology and Cell Biology at Ohio State characterized the effects of platelet-activating factor in the enteric nervous system and published their findings in the Am J Physiology. Xia is funded by a National Institute of Diabetes & Digestive & Kidney Disease Clinical Investigator Training Grant.
Ischemic spinal cord injury: Hamdy Elsayed- Awad, MD, is examining biochemical changes in central and peripheral compartments of patients undergoing surgical repair of an aortic aneurysm. This clinical paradigm in a large number of patients is expected to unravel mechanisms of ischemic spinal cord injury and paraplegia in thoracoabdominal aortic aneurysm (TAAA) patients. Together, the TAAA human model, a large animal/ clinical model of paraplegia and a mouse model of paraplegia suitable for genomic/mechanistic studies should provide a path from lab bench to bedside in testing new interventions to protect against paraplegia in TAAA patients.
Brain-Imaging: Functional magnetic resonance imaging studies (fMRI) on pain stimulation are contaminated with physiologic noise (e.g., cardiopulmonary parameters change significantly in response to pain). Robert Small, MD, in collaboration with Biomedical Engineering, Radiology and other departments at Ohio State, is identifying and subtracting physiologic noise in fMRI imaging of the brain from the response to a painful stimulation. They presented their data at the national meeting of the International Society for Magnetic Resonance in Medicine.