Flow-mediated dilation analysis coupled with nitric oxide transport to enhance the assessment of endothelial function

J Appl Physiol (1985). 2021 Jul 1;131(1):1-14. doi: 10.1152/japplphysiol.00039.2021. Epub 2021 Apr 8.

Abstract

Flow-mediated dilation (FMD), mainly mediated by nitric oxide (NO), aims to assess the shear-induced endothelial function, which is widely quantified by the relative change in arterial diameter after dilation (FMD%). However, FMD% is affected by individual differences in blood pressure, blood flow, and arterial diameter. To reduce these differences and enhance the assessment of FMD to endothelial function, we continuously measured not only the brachial artery diameter and blood flow with ultrasound but also blood pressure with noninvasive monitor during standard FMD test. We further constructed an analytical model of FMD coupled with NO transport, blood flow, and arterial deformation. Combining the time-averaged and peak values of arterial diameter, blood flow, and pressure, and the modeling, we assumed the artery was completely healthy and calculated an ideally expected FMD% (eFMD%). Then, we expressed the fractional flow-mediated dilation (FFMD%) for the ratio of measured FMD% (mFMD%) to eFMD%. Furthermore, using the continuous waveforms of arterial diameter, blood flow, and pressure, the endothelial characteristic parameter (ϵ) was calculated, which describes the function of the endothelium to produce NO and ranges from 1 to 0 representing the endothelial function from healthiness to complete loss. We found that the mFMD% and eFMD% between the young age (n = 5, 21.2 ± 1.8 yr) and middle age group (n = 5, 34.0 ± 2.1 yr) have no significant difference (P = 0.222, P = 0.385). In contrast, the FFMD% (P = 0.008) and ϵ (P = 0.007) both show significant differences. Therefore, the fractional flow-mediated dilation (FFMD%) and the endothelial characteristic parameter (ϵ) may have the potential for specifically diagnosing the endothelial function.NEW & NOTEWORTHY FMD% is affected by various factors, which limits its ability to assess the endothelial function. We developed an analytical model of FMD process coupled with nitric oxide based on the mathematical modeling and physiological measurements. Two model-derived indicators (FFMD% and ϵ) were introduced based on the modeling. Our results indicated that FFMD% and ϵ may have the potential to distinguish the endothelial function between the young- and middle age groups.

Keywords: endothelial function; flow-mediated dilation; nitric oxide; physiological modeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brachial Artery / diagnostic imaging
  • Dilatation
  • Endothelium, Vascular
  • Humans
  • Middle Aged
  • Nitric Oxide*
  • Regional Blood Flow
  • Vasodilation*

Substances

  • Nitric Oxide