The CCIR provides the framework to optimize the translation of experimental work into novel clinical approaches for diagnosis, treatment and prevention of diseases/syndromes encountered in the ICU. Hospital critical care units provide specialized interdisciplinary care to patients with life threatening or potentially threatening conditions, typically involving one ore more organ system failures.
Research at CCIR studies the causes and consequences of remote organ injury and multiple organ dysfunctions during sepsis/systemic inflammation, the leading cause of death in Intensive Care Units.
What is sepsis/systemic inflammation?
Sepsis is a life-threatening complication of an infection. Sepsis occurs when chemicals released by bacteria (or other pathogens) enters into the bloodstream triggering inflammatory response throughout the body (i.e. systemic inflammation). This inflammatory response can lead to changes that damage multiple organ systems, causing them to fail. Similarly, severe trauma to one or multiple body parts/organs can result in production of inflammatory chemicals by our own body, resulting in the development of systemic inflammation. To date there is/are no specific treatment(s) to fight against systemic inflammation.
Major research aims:
- Mechanisms of inflammatory organ injury/dysfunction
- Resolution of inflammation
- Development of therapeutic approaches
The following methodologies/approaches provide the background for the specific research projects:
- Cell and tissue culture
- Intravital videomicroscopy
- Isolated perfused organ systems
- Small animal models: fecal peritonitis, ischemia/reperfusion, blast injury, pneumonia, limb compartment syndrome, aged animals
- Translational Research Centre with standard operating procedures for processing and storing human biological samples
Multidisciplinary teams consisting of both basic and clinical scientists work together to facilitate research discoveries and the translation of findings related to:
Sepsis-associated encephalopathy, sepsis-associated myocardial and lung dysfunction and sepsis-associated microcirculatory dysfunction are the prime targets for clinical and basic research investigation.
The group uses both in vivo (hemorrhagic shock/resuscitation, blast injury, limb compartment syndrome) and in vitro (anoxia/reoxygenation, pressure-induced biaxial stretching) approaches to understand underlying mechanism(s) involved in trauma-induced lung, brain, heart, gut, and skeletal muscle injury/dysfunction.
The clinical focus of this group encompasses sepsis-induced lung injury, ventilation-induced lung injury, cystic fibrosis as well as several other clinical entities. Mechanistically, the research focuses on the role of inflammatory cells (neutrophilic leukocytes and macrophages), metalloproteinases and their inhibitors, pulmonary surfactant and antimicrobial peptides in the complex pathophysiology of these diseases.
Intravital videomicroscopy approaches are used to examine microvascular function (e.g. capillary perfusion, tissue oxygenation, oxidant stress, tissue injury, apoptosis, inflammatory cell recruitment etc.) under homeostatic and pathologic (i.e. sepsis, trauma) conditions.
The group focuses on understanding the molecular mechanism(s) and developing new treatments for myocardial ischemia/reperfusion-, sepsis-, doxorubicin- and diabetes-induced heart injury/dysfunction.
Research in this group focuses on understanding the mechanisms regulating organ/tissue-specific (e.g. brain, lung, liver, skeletal muscle, large blood vessels etc.) vascular endothelial cell activation/injury and subsequent interaction with inflammatory cells (e.g. neutrophils and macrophages) under experimental conditions of sepsis, trauma, and diabetes. Carbon monoxide-releasing molecules (CORMs) are investigated as potential modulators of inflammatory response.