Introduction

Cardiopulmonary bypass (CPB) is currently performed in infants and newborns for surgical correction of congenital heart diseases (CHDs).¹ 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.² 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.³

Systemic microvascular dysfunction during CPB results in inadequate blood flow, organ perfusion and oxygen delivery to the tissues.⁴ We have shown, using laser Doppler perfusion monitoring (LDPM) (a non-invasive method coupled with local heating of the skin), that the microcirculatory bed of the skin of the forehead is an appropriate model for the study of microvascular reactivity and tissue perfusion in cardiovascular surgery with CPB in adults.⁵ Actually, local thermal hyperemia (LTH) is a useful method in the evaluation of systemic microvascular endothelial function.^5,6 In addition, using LDPM, we demonstrated that microvascular dysfunction and hypoperfusion occur during CPB in surgical correction of congenital heart disease in infants and children, despite adequate macrohemodynamic parameters.⁷ The mismatch between macro- and microcirculation in severely ill patients with septic or cardiogenic shock, which can be misleading to an adequate clinical management of these patients, has also stimulated the search for new methods to monitor microcirculatory perfusion in the intensive care units.⁸

Of note, the release of nitric oxide (NO) from the constitutive endothelial isoform of nitric oxide synthase (eNOS) is reduced during CPB in adult patients.⁹ NO is a potent endothelium-derived endogenous vasodilator, and its depletion during CPB under non-pulsatile flow can lead to vasoconstriction, and consequently reduced organ perfusion. Plasma NO_x (NO₂^– / NO₃^–), steady metabolites of NO, which have been used as markers of systemic NO bioavailability, as their levels reflect changes in eNOS activity in humans.¹⁰ Therefore, the aim of the present study was to investigate whether a reduction of NO systemic bioavailability is associated with endothelial-dependent microvascular dysfunction in infants and children, during on-pump cardiac surgery for the correction of acyanotic CHD.