202. Nitric Oxide Delivery via Oxygenator Protects Against Cardiopulmonary Bypass-Associated Acute Kidney Injury: Histopathologic and Biomarker Evidence from an Ovine Model
Duke
Durham, NC
United States - Contact Me
A native of North Carolina, Dr. Clark obtained a bachelor's degree in mechanical engineering from the Massachusetts Institute of Technology (1990) and then served on active duty as a civil engineering officer in the Air Force in Glendale, Arizona (1991-93). He graduated from the University of North Carolina School of Medicine (1997) and subquently completed training in general surgery at the University of North Carolina (2004), thoracic surgery at the University of Virginia (2006), and congenital cardiac surgery at Boston Children's Hospital (2007). Dr. Clark joined the faculty at the Penn State College of Medicine (2007) and now serves as Professor and Chief of Pediatric Cardiac Surgery at the Penn State Health Children's Hospital in Hershey, Pennsylvania.
Keck Hospital USCLAC+USC medical center
SANTA MONICA, CA
United States - Contact Me
Jason Greenberg graduated from Saint Louis University School of medicine, where he also completed a categorical internship in general surgery, before beginning a research fellowship in the congenital cardiothoracic surgery department at Cincinnati Children's Hospital Medical Center.
Abstract
Methods: Using a survival ovine CPB model, AKI was induced by implementing a low-flow CPB state (40 cc/kg; goal serum lactate 6 mmol/L) for two hours, followed by return to full-flow (80 cc/kg) for two hours. The experimental group (n=6) received NO via the oxygenator in the CPB circuit whereas the control group (n=5) did not receive NO. To study AKI incidence and progression, the animals were survived 72 hours post-CPB initiation before euthanasia and kidney harvest for histopathologic analyses. Serial serologic biomarkers (including LDH and creatinine) were obtained.
Results: The baseline characteristics and intraoperative hemodynamics of both groups were equivalent with regards to weight, CPB time, fluid administration, urine output (UOP, cc/kg/hr), heart rate, arterial pH, arterial pO2, and lactate (p>0.1 for all). Postoperatively, UOP, heart rate, respiratory rate, and SpO2 were comparable between groups (p>0.1 for all). As shown in the Figure (top panel), distinct serologic trends were seen in which post-CPB elevations in LDH and creatinine were much more pronounced in the control group compared to the NO group. Change in creatinine from baseline (pre-CPB) was significantly greater in the control group than NO at 16, 24, and 48 hours (p<0.05 for all). Upon histopathologic analysis, moderate/severe AKI occurred in 60% (3/5) control animals versus 0% (0/6) NO animals, with epithelial necrosis, tubular slough, cast formation, and glomerular edema occurring in the control but not NO group (Figure, bottom panel). Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group (all members) than the NO group (p=0.049).
Conclusions: In this survival ovine CPB model, NO administered via the CPB circuit demonstrated serologic and histopathologic evidence of protection from AKI. These results provide insight into one potential mechanism for CPB-associated AKI and supports the continued study of the use of NO via the CPB circuit for prevention of AKI.