Nitric Oxide Delivery via Oxygenator Protects Against Cardiopulmonary Bypass-Associated Acute Kidney Injury: Histopathologic and Biomarker Evidence from an Ovine Model

Presented During:

Monday, May 8, 2023: 7:30AM - 7:45AM
Los Angeles Convention Center  
Posted Room Name: 403B  

Abstract No:

202 

Submission Type:

Abstract Submission 

Authors:

Jason Greenberg (1), Spencer Hogue (1), Muhammad Aanish Raees (1), Hosam Ahmed (1), William A Abplanalp (1), Amalia Guzman-Gomez (1), Zakia Abdelhamed (1), Karthik Thangappan (1), James Reagor (1), James Rose (2), Michaela Collins (3), Jennifer Kasten (4), Stuart Goldstein (2), David Cooper (1), Farhan Zafar (1), David Morales (1)

Institutions:

(1) The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, (2) Division of Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, (3) Division of Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, CA, (4) Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Submitting Author:

Jason Greenberg    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center

Co-Author(s):

Spencer Hogue    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
Muhammad Aanish Raees    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
Hosam Ahmed    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
William A Abplanalp    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
Amalia Guzman-Gomez    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
Zakia Abdelhamed    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
Karthik Thangappan    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
James Reagor    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
James Rose    -  Contact Me
Division of Nephrology, Cincinnati Children's Hospital Medical Center
Michaela Collins    -  Contact Me
Division of Nephrology, Cincinnati Children's Hospital Medical Center
Jennifer Kasten    -  Contact Me
Division of Pathology, Cincinnati Children's Hospital Medical Center
Stuart Goldstein    -  Contact Me
Division of Nephrology, Cincinnati Children's Hospital Medical Center
David Cooper    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
Farhan Zafar    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center
David Morales    -  Contact Me
The Heart Institute, Cincinnati Children's Hospital Medical Center

Presenting Author:

Jason Greenberg    -  Contact Me
Cincinnati Children’s Hospital Medical Center

Abstract:

Objective: Between 30-50% of children undergoing cardiac surgery develop cardiopulmonary bypass (CPB)-associated acute kidney injury (AKI). Several human studies have associated nitric oxide (NO) administration via the CPB circuit with decreased incidence of AKI, although histopathologic and serologic evidence of NO efficacy for AKI attenuation are lacking.

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.

CONGENTIAL:

Basic and Translational Research

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Supporting Image: AATS2023_AKI_AbstractFigure.png
 

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Keywords

Keywords - Adult

Perioperative Management/Critical Care - Perioperative Management/Critical Care
Perioperative Management/Critical Care - Renal Failure/Acute Kidney Injury

Keywords - Congenital

Perioperative Management/Critical Care - Perioperative Management/Critical Care
Perioperative Management/Critical Care - Renal Failure/Acute Kidney Injury
Procedures - Procedures