van Kraaij Sebastiaan J W, Eveleens Maarse Boukje Charlotte, Hoevenaars Femke P M, Warnke Ines, de Kam Marieke L, Moerland Matthijs, Gal Pim
Centre for Human Drug Research, Leiden, The Netherlands.
Leiden University Medical Centre, Leiden, The Netherlands.
Clin Physiol Funct Imaging. 2025 Jan;45(1):e12904. doi: 10.1111/cpf.12904. Epub 2024 Sep 23.
Endothelial dysfunction is a pathophysiological change preceding many cardiovascular events. Measuring improvements of endothelial function is challenging when function is already optimal, which may be remediated using a physiological challenge. This study aimed to determine whether imaging assessments can detect microvascular effects of a mixed meal tolerance test (MMTT).
Twenty healthy volunteers (age ≥45 and ≤70 years) underwent two MMTTs at the beginning (Day 1) and end (Day 84) of a twelve-week period. Imaging methods included laser speckle contrast imaging (LSCI) combined with post-occlusive reactive hyperaemia (PORH) and local thermal hyperaemia (LTH) challenges, passive leg movement ultrasonography (PLM), and sidestream dark field microscopy (SDFM). Measurements were conducted pre-MMTT and at 5 timepoints post-MMTT for PLM and SDFM and 3 timepoints post-MMTT for PORH and LTH.
No consistent effects of the MMTT were detected on LSCI LTH, PLM and SDFM endpoints. LSCI PORH maximum perfusion was significantly suppressed 46, 136, and 300 min post-MMTT administration on Day 1, while residual perfusion decreased significantly 46 and 136 min post-MMTT on Day 1. However, when repeated on Day 84, PORH endpoints were not significantly affected by the MMTT.
SDFM, PLM and LSCI LTH endpoints displayed high intra-subject variability and did not detect consistent effects of MMTT. LSCI PORH endpoints displayed the lowest intra-subject variability of all assessed endpoints and were affected by the MMTT on Day 1, but not on Day 84. Further standardization of methods or more robust challenges to affect vascular endpoints may be needed.
内皮功能障碍是许多心血管事件之前的一种病理生理变化。当内皮功能已经处于最佳状态时，测量其功能改善具有挑战性，而生理刺激可能有助于解决这一问题。本研究旨在确定成像评估是否能够检测混合餐耐量试验（MMTT）的微血管效应。
20名健康志愿者（年龄≥45岁且≤70岁）在为期12周的试验开始时（第1天）和结束时（第84天）分别进行了两次MMTT。成像方法包括激光散斑对比成像（LSCI）结合闭塞后反应性充血（PORH）和局部热充血（LTH）刺激、被动腿部运动超声检查（PLM）以及侧流暗视野显微镜检查（SDFM）。对于PLM和SDFM，在MMTT前以及MMTT后5个时间点进行测量；对于PORH和LTH，在MMTT后3个时间点进行测量。
未检测到MMTT对LSCI LTH、PLM和SDFM终点有一致的影响。在第1天，MMTT给药后46、136和300分钟，LSCI PORH的最大灌注显著受到抑制，而在第1天MMTT后46和136分钟，残余灌注显著降低。然而，在第84天重复试验时，PORH终点未受到MMTT的显著影响。
SDFM、PLM和LSCI LTH终点显示出较高的受试者内变异性，未检测到MMTT的一致影响。LSCI PORH终点在所有评估终点中显示出最低的受试者内变异性，在第1天受到MMTT的影响，但在第84天未受影响。可能需要进一步规范方法或采用更有力的刺激来影响血管终点。
