Influence of Macitentan on the Vascular Tone and Recruitment of Finger Capillaries Under Hypobaric Hypoxia in High Altitude.

Betge, Stefan, Stefan Drinda, Thomas Neumann, Laura Bäz, Alexander Pfeil, Christian Schulze, Ralf Mrowka, Christian Jung, and Marcus Franz. Influence of macitentan on the vascular tone and recruitment of finger capillaries under hypobaric hypoxia in high altitude. High Alt Med Biol . 21:336-345, 2020. Introduction: Acute normobaric (NH) and hypobaric hypoxia (HH) has effects on the vascular tone of larger arteries and may have effects on the microcirculation. These effects may be noninvasively detectable by automated devices. A part of these effects may be mediated by endothelin (ET) and should be influenced by macitentan (MAC), a dual endothelin receptor antagonist (ERA). Methods: We used photoplethysmographic sensors, fingertip volume sensors, nailfold capillaroscopy, and laser Doppler probes at rest and after a 5-minute forearm ischemia in healthy study subjects under NH, under HH, and under HH plus a single dose of MAC. Results: NH at simulated 4000 m led to increased heart rates (HR) and pulse wave velocities (PWV) and reduced augmentation index (AIX). The values for the AIX showed a high SD and differed between the used devices. At simulated 5500 m, only baseline mean value (BMV; EndoPAT) showed a further change, indicating less filled capillaries of the fingertips. HH (2978 m) increased HR, blood pressure values, and PWV. Focusing on the microcirculation of the fingertips, HH reduced the BMV and the nailfold capillary density and the postischemic capillary recruitment. MAC had no effect on the BMV, but antagonized the effects of HH on the nailfold capillaries and led to a strongly increased postischemic diameter of the arterial limbs. Concordantly, the postischemic blood flow velocity increment, measured through ultrasound Doppler, was increased at ALT+MAC. Conclusions: The BMV may be a parameter for changes of the microcirculation of the finger tips. A single dose of MAC blocked hypoxia-induced capillary rarefaction and enhanced postischemic hyperemia of the fingertips. These results indicate the importance of ET-1 for the regulation of the microcirculation under hypoxia. The German Registry of Clinical Studies (DRKS) ID: 00005459.