Reduced Systemic Nitric Oxide Bioavailability Parallels Microvascular Endothelial Dysfunction during Cardiopulmonary Bypass

Introduction

Cardiopulmonary bypass (CPB) is currently performed in infants and newborns for surgical correction of congenital heart diseases (CHDs). CPB exposes the body to extreme, nonphysiologic conditions that initiate a systemic inflammatory response accompanied by vasomotor dysfunction, and can lead to multiple organ dysfunction. Additionally, CPB has been linked to activation and injury of endothelial cells, which is associated with global inflammatory response, triggering of the coagulation system and subsequent organ dysfunction, not only in adult patients, but particularly in infants and newborns.

Methods

This longitudinal observational study included 47 consecutive pediatric patients with acyanotic heart defects, aged between 1 month and 9 years, undergoing corrective cardiac surgery at a tertiary public Brazilian hospital. The study was undertaken according to the Declaration of Helsinki and was approved by the ethics committee of the institution. Parents or legal tutors of the study participants gave written informed consent. The anesthetic procedures occurred under CPB, with mild to moderate hypothermia (32-34° C). Mean arterial pressure was kept between 45-60 mmHg.

Discussion

NO has a key role in the regulation of endothelial function and microvascular inflammation. CPB induces a generalized inflammatory response, triggered at least in part by ischemia–reperfusion injury, which contributes to myocardial dysfunction and reduced cardiac output, and is related to NO metabolism, among other mechanisms. The current study shows a reduction of NO during CPB in children, which parallels the objective evidence of microvascular dysfunction. This underscores prior evidence of NO reduction during cardiac surgery, what has led to studies using NO administration to reduce bypass-induced inflammation in children undergoing cardiac surgery. Therefore, data from this study may support the use of microcirculatory monitoring during CPB, with guided therapeutic interventions.

Conclusions

The impairment of microvascular endothelial function during CPB in cardiac surgery for the correction of congenital heart defects appears to be related to a reduced systemic bioavailability of NO, resulting from the inflammatory and pro-oxidative response typical of this surgical procedure.