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Critical Care Medicine - Research


 

Overview

The Section of Critical Care Medicine has a thriving and diverse set of bench, translational, and clinical research programs designed to advance the understanding of and quality of medical care provided to critically ill children.

The Pediatric Critical Care Clinical Research Program supports clinical and translational research projects within the Children’s Hospital Colorado Pediatric Intensive Care Unit. With the contribution of many of the Critical Care faculty as well as investigators from outside the Section, the program provides the infrastructure to execute investigator-initiated and multi-center studies, including feasibility analysis, research management, and mentorship and research training. The program participates in the Virtual PICU System (VPS), a clinical database dedicated to standardized data sharing and benchmarking among pediatric ICUs. Present studies in the PICU include: the role of the airway microbiome in ventilator-associated pneumonia, the impact of Vitamin D in respiratory disease in formerly preterm infants, the association of hyponatremia with outcome in critical illness, and pathophysiology of acute lung injury. The program also participates in multiple multicenter studies including the Genetic Epidemiology of Influenza in Children, Heart and Lung Injury – Pediatric Insulin Titration Trial, and Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care.

The Developmental Lung Biology Laboratory and Cardiovascular Pulmonary (CVP) Research Laboratory at the Anschutz Medical Campus at the University of Colorado Denver represent the backbone of bench research within the Section of Critical Care Medicine. A large multidisciplinary group of investigators from diverse departments within the University including the Departments of Medicine (Pulmonary and Cardiology), Pediatric (Critical Care, Pulmonary, Cardiology, GI) and the Department of Bioengineering work to advance the understanding of the cellular and molecular basis of injury to the developing lung and lung pulmonary circulation, an area of research that is closely related to problems encountered on a daily basis in the PICU.

The research of the CVP includes studies at the basic molecular and cellular levels, as well as translational biology and physiology studies. The laboratory receives substantial funding from the NIH, the American Heart Association, and the American Lung Association.

A program project grant, which is the centerpiece of the Cardiovascular Pulmonary Research Laboratory, comprises four scientific projects focused on studies of the mechanisms of hypoxic pulmonary hypertension (PH). The proposed studies are collectively founded on the hypothesis that the pathogenesis of hypoxic PH involves both functional (vasoconstriction and wall stiffening) and structural (vascular wall thickening) components, and that both components involve hypoxia-induced alterations in resident cell function as well as recruitment and interactions with inflammatory and/or progenitor cells. Four highly collaborative and interactive projects will provide new insights into the cellular/molecular mechanisms of chronic hypoxic pulmonary vasoconstriction and vascular stiffening and remodeling and may lead to novel, more effective therapy for hypoxic PH. The basic work is supported by two major Core facilities. One provides the facilities to expose animals (mice, rats, calves, and humans) to acute and chronic hypobaric hypoxia. In addition, state-of-the-art equipment is provided for hemodynamic assessments of the pulmonary and systemic circulations. A large Cell Culture and Histopathology Core also supports the scientific projects.

In the Developmental Lung Biology Laboratory, which works cooperatively with the Pediatric Heart Lung Center, directed by Dr. Steven Abman, research work is focused on determining mechanisms involved in lung vascular growth. The centerpiece for the laboratory is a Specialized Centers of Clinically Oriented Research (SCCOR) Program. The SCCOR Program generates clinical and basic information that will provide insight into the mechanisms contributing to the pulmonary vascular abnormalities that characterize BPD. This is done by evaluating current available therapies aimed at reducing lung injury and restoring vascular and lung growth and by examining animal models for new approaches to ameliorating perinatal lung injury and restoring vascular and lung growth. Two clinical and two basic projects address these objectives. The clinical projects evaluate (1) the impact of inhaled nitric oxide (iNO) on BPD, and (2) the development of improved techniques to assess the presence of pulmonary hypertension and the responses to therapy in infants with pulmonary hypertension. The two basic projects dissect the mechanisms contributing to lung vascular remodeling in murine, rodent, ovine, and bovine models and evaluate the effects of novel pharmacologic agents on lung vascular disease in these models. Collaborative interactions with National Jewish Health, the Center for Bioengineering, and the Sections of Pulmonology, Neonatology, and Cardiology drive this program forward.

The faculty in the CVP collaborate in a successful training program; weekly seminars and shared resources that all contribute to the exceptional research environment. There are also active collaborations with investigators at National Jewish Hospital, the University of Colorado High Altitude Research Institute. Important new collaborations are also now ongoing on the pathogenesis of ischemic neuronal injury in the immature brain along with researchers in Neurobiology.