RAJNI KUMRAH, PhD
PhD, Postdoctoral (Senior Research Fellow)
Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Chandigarh, Chandigarh, India
Background Several long-term complications, including vascular endothelial dysfunction (ED), have been associated with KD. The persistent inflammatory cascade in KD is believed to damage the arterial vasculature by increased production of reactive oxygen species (ROS) by neutrophils and an excess of nitric oxide (NO). This results in oxidative stress (OS) that leads to the development of ED and atherosclerosis. There is paucity of literature on OS in KD patients on follow-up. We explored markers of OS in KD patients on follow-up in the context of ED seen in this condition Methods This is a single-centre, prospective study conducted from July 2017 to July 2022. We enrolled 65 patients of KD as per AHA 2017 (clinical parameters shown in figure1) and 20 age matched healthy controls (HC). Patients were categorised as follows: Group 1: (n=19; >6 months -1.5 years on follow-up); Group 2: (n=24; >1.5 - 3 years on follow-up); and Group 3: (n=22; >3 - 4.5 years on follow-up). Twenty-nine patients had CAAs [transient (n=13), persistent (n=16)] and 36 patients had no CAAs. Serum levels of extracellular nitric oxide (nitrite, nitrate) were estimated by spectrophotometric kit-based method and absorption was measured at 540 nm. ROS was assessed by dihydrorhodamine 123 assay (Figure 3a) using Navios flowcytometer and analysed using Kaluza software. Data were presented as delta median fluorescent intensity (∆MFI = MFI Stimulated-MFI Unstimulated). Results were analyzed using Graphpad Prism and IBM SPSS. Results Statistical analysis showed comparable levels of nitrite and nitrate among patients in all 3 groups. Higher nitrate was noted in patients as compared to HC (ns) (Figure 2a); and in patients with CAAs when compared to those without CAAs (Figure 2c). ROS estimation showed higher ∆MFI in KD patients than HC- however, the difference was not significant (Figure 3b). ∆MFI was higher in patients with CAAs in group 1 when compared to patients without CAAs while in group 2 & 3, the ∆MFI was comparable for patients with and without CAAs. ROS had non-significant positive correlation with CRP and pro-BNP. Nitrite and ROS had negative correlation with coronary artery dimensions while nitrate showed positive correlation. Conclusion Higher extracellular nitrate in patients accounts for an aberrant immune response and could be linked with disease pathogenesis and development of CAAs. Elevated ROS suggests an association of OS induced ED in KD patients on follow-up. Persistence of OS may explain the ED seen in patients with KD on follow-up.