4.5 Article

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

Journal

JOURNAL OF APPLIED PHYSIOLOGY
Volume 131, Issue 1, Pages 1-14

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00039.2021

Keywords

endothelial function; flow-mediated dilation; nitric oxide; physiological modeling

Funding

  1. National Natural Science Research Foundation of China [61533016, 11827803, 31971244, 31570947, 61705184, 11772036, U20A20390]
  2. National key research and development program of China [2016YFC1101101, 2016YFC1102202]
  3. 111 Project [B13003]

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This study developed an analytical model of FMD process coupled with nitric oxide, introducing FFMD% and epsilon as potential indicators to distinguish endothelial function between young and middle age groups. Results showed no significant difference in mFMD% and eFMD% between the groups, but significant differences were found in FFMD% and epsilon, suggesting potential for specific diagnosis of endothelial function.
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 (epsilon) 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 +/- 2.1yr) have no significant difference (P = 0.222, P = 0.385). In contrast, the FFMD% (P = 0.008) and epsilon (P = 0.007) both show significant differences. Therefore, the fractional flow-mediated dilation (FFMD%) and the endothelial characteristic parameter (epsilon) 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 e) were introduced based on the modeling. Our results indicated that FFMD% and e may have the potential to distinguish the endothelial function between the young- and middle age groups.

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