Congenital: Perioperative Management: Basic Science
Exogenous nitric oxide delivery protects against cardiopulmonary bypass–associated acute kidney injury: Histologic and serologic evidence from an ovine model

Read at the 103rd Annual Meeting of The American Association for Thoracic Surgery, Los Angeles, California, May 6-9, 2023.
https://doi.org/10.1016/j.jtcvs.2023.03.030Get rights and content

Abstract

Objective

Several human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass–associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking.

Methods

By using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained.

Results

Baseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P > .10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P > .10) between groups. Post–cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P < .05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P = .012).

Conclusions

In a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass–associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury.

Section snippets

Materials and Methods

Study approval was obtained from the Cincinnati Children's Hospital Institutional Animal Care and Use Committee (protocol #2020-0076, approved March 17, 2021). All animals received humane care in compliance with the Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for Care and Use of Laboratory Animals prepared by the National Academy of Science and published by the National Institutes of Health.

Intraoperative and Postoperative Characteristics

A total of 11 (n = 6 NO-treated, n = 5 control) animals were included in the study (Table 1). Weight (NO treated: mean 22 ± 3.3 kg, control: mean 23 ± 6.1 kg, P = .643) and age (NO treated: mean 4.8 ± 2.9 mo., control: mean 5.5 ± 2.1 mo., P = .645) at time of surgery were comparable between groups. As shown in Table 2, CPB times were equivalent between groups, as were the total volumes of intraoperative fluid administration and urine output (all P > .50). Average intraoperative bladder

Discussion

In a survival ovine model of CPB-associated AKI, exogenous NO infused through the bypass circuit intraoperatively appeared efficacious in decreasing the development of postoperative severe kidney injury, as evidenced by attenuation of certain postoperative biomarkers associated with AKI and preservation of renal tubular structure (Figure 5). The first notable implication of the study is the efficacy of NO in a cardiac surgical animal model, which allowed for the controlled management and

Conclusions

In the present ovine model of CPB-associated AKI, exogenous NO infused through the oxygenator provided biomarker and histologic evidence of protection against postoperative AKI. The current study mirrors the results of clinical trials, which have shown NO to attenuate postoperative AKI in adult patients undergoing cardiac surgery, and provides several important insights into the serologic and histologic effects of NO in AKI prevention. The results add to the literature supporting the use of

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