|Critical Care Research|
Critical Care and Perioperative Medicine Division Research
During the last decade, members of the Critical Care Division have developed highly successful programs which in collaboration with faculty members from other departments and university centers, pursues basic, translational and clinical research projects related to contribution of pathogens and reactive species to lung epithelial injury, basic mechanisms by which nitric decreases injury to the systemic circulation following ischemia-reperfusion, nitric oxide control of smooth muscle tone, and novel drug strategies for promoting tissue protection during metabolic "stress" (e.g., ischemic episodes, acute inflammatory responses).
Several faculty members of the Critical Care Division contribute to the research and teaching missions of the Center of Free Radical in Biology and Medicine, established by Dr. Bruce A. Freeman, acknowledged as a one of the world's strongest centers focusing on the roles of reactive inflammatory mediators (free radicals, oxidants) in surgical, critical care, immunological, cell signaling and environmental problems.
Active Research Protocols
Lung Injury Research (Dr. Sadis Matalon)
Current research efforts in Dr. Matalon's laboratory focus on understanding the mechanisms by which viruses and reactive oxygen nitrogen species damage the activity of lung ion channels and in developing countermeasures to lung injury caused by chlorine inhalation (for additional details and recent publications see http://www.sadismatalon.com/). Recent findings include: (1) the elucidation of the mechanisms by which Respiratory Syncytial Virus (RSV), the most common cause of bronchiolitis and pneumonia among infants under 1 year of age and a common cause of pneumonia among the elderly and immunocompromised patients, damages the lungs;(2) the demonstration of the dual role of nitric oxide in modulating sodium and chloride transport across the respiratory and alveolar epithelial and (3) the development of novel therapeutic regimes aimed to decrease lung injury following exposure to chlorine gas.
Biological Roles of Nitric Oxide & Reactive Oxygen Species (Drs. Jack Lancaster and Karen Iles)
Internationally recognized nitric oxide expert and Editor-in-Chief of the journal Nitric Oxide: Biology & Chemistry, Dr. Lancaster has for more than thirty years investigated the biochemistry and molecular biology of NO and its interactions at the cellular and subcellular levels. The dynamics of NO in blood and tissue and its role in injury (inflammation, infection, ischemia/reperfusion) have been the main focus, dealing particularly with interactions between NO and reactive oxygen species. Techniques utilized for study include electron paramagnetic resonance spectroscopy for in vitro and in vivo detection of NO and its actions and electrochemical detection of NO. Recently cellular and biochemical mechanisms of cytokine and production and their effects during immune activation (sepsis, allograft rejection) and oxidative injury during disturbances in oxygen metabolism (ischemia/reperfusion, sepsis, oxidative burst) have been a focus. In American Heart Association-funded studies, Dr. Iles is investigating a spin-off of these studies: the role of Heme-oxygenase-1 in the oxidative state (nitric oxide and reactive oxygen species) in the lung.
Cardioprotective Strategies/Ischemia-Reperfusion Injury (Dr. Dale Parks)
As Director of UAB's Center for Wine and Cardiovascular Health, Dr. Parks, with NIH and industry support, has created an infrastructure to investigate the mechanisms whereby dietary polyphenols and ethanol reduce the morbidity and mortality associated with coronary heart disease and reduce hepatic, renal, pulmonary, myocardial and vascular injury. Using whole animal models of disease (mouse models of atherosclerosis), ex vivo assessments of tissue function (video dimension analysis), cellular models (mouse endothelial cells from knock out animals and transfection) for study of regulation of these cardioprotective proteins and molecular systems for identification of oxidant/antioxidant-responsive elements and transcription factors. The ultimate goal is to provide mechanistic insight into the pathoetiology of the cardiovascular disease as well as providing a rationale basis for the development of therapeutic agents designed to limit the oxidant-induced injury.
Molecular Mechanisms of Anesthetic Drug Action (Drs. Keith Jones and John Streiff)
Drs. Jones and Streiff, with NIH funding, have sought to use a variety of biophysical techniques to determine how protein activities are altered when volatile anesthetics bind. They have developed theoretical approaches to identify potential anesthetic targets and use docking algorithms to predict the structures and binding affinities of anesthetic protein complexes. Biochemical techniques have been used to assay the effect of anesthetic binding on the function of protein targets. Calorimetry and fluorescence spectroscopy techniques have been used to measure anesthetic binding affinities. High resolution nuclear magnetic resonance (NMR) spectroscopy is used to experimentally verify that anesthetics bind to proteins and determine the subsequent effects on the structure and internal dynamics of the protein. Stopped flow spectroscopy and surface plasmon resonance methods are used to determine the effect of anesthetic binding on the kinetics of protein-protein or protein-substrate interactions. Together, these techniques have provided a comprehensive picture of the effects of anesthetic binding on the structure, dynamics, and function of proteins.