Evaluation of the endothelial glycocalyx in premature neonates by measurement of the perfused boundary region (PBR)

Rajwich, Lea (2021): Evaluation of the endothelial glycocalyx in premature neonates by measurement of the perfused boundary region (PBR) = Untersuchung der endothelialen Glykokalyx be Frühgeborenen durch Messung der Perfused Boundary Region (PBR). Dissertation, LMU München: Medizinische Fakultät

Abstract

The endothelial glycocalyx (GCX) is acknowledged as a pivotal juncture in the development of vascular pathologies in sepsis [73], diabetes [53, 66-68, 155], cardiovascular [65, 69-72] and other diseases. Moreover, impaired microcirculation leading to perivascular edema [27] and altered rheological behavior [15, 20-22] is likely due to reduced endothelial GCX. Perinatal alterations in GCX have been investigated in vivo and in vitro [77, 104] and functional and structural alterations of the microcirculation in premature neonates have been described in previous studies [86, 89, 109, 118]. However, now the endothelial GCX, as a possible mediator, is increasingly highlighted in understanding perinatal pathologies in microcirculatory vessel development [77, 104]. Further studies on the perinatal glycocalyx and the corresponding microcirculation were the primary aim of this study. A prospective study was conducted including 39 premature infants born at the Perinatalzentrum Frauenklinik Maistrasse of the Ludwig-Maximilian- University, Munich, Germany. Data on the GCX in 85 mature babies obtained in a parallel study, served as control. The ethical committee of the Ludwig-Maximilian-University approved the study. The GCX was assessed indirectly by the capillary endothelial GCX perfused boundary region (PBR), an internationally validated, inverse gauge for microcirculation [30, 105, 106, 138, 145]. PBR was obtained transcutaneously using non-invasive SDF-imaging of blood flow in the microcirculation of the participants’ ear helix [30]. The basic requirements for a valid image quality were guaranteed [115] and the GlycoCheck™- software automatically calculated the PBR of video segments. Longitudinal measurements were planned at the newborn screening (NS) and run around every full postnatal week ± one day; vital und laboratory parameters were also obtained. Within a 12 hours frame before or after measurement, a blood sample was drawn and recorded. PBR measurements of premature neonates were documented in 109 cases and blood samples at the same time were obtained in 106 cases. The measurements were stratified between very premature (group A [gestational age at birth < 30w + 0d]), moderate premature (group B [30w + 0d ≤ gestational age at birth < 37w + 0d]), and mature neonates (control group [gestational age at birth ≥ 37w + 0d]). For further evaluation, the starting point at NS was approached to visualize the PBR at birth. A significant increase between PBR (decrease in GXC size) and gestational age at birth was observed across the three groups. PBR at the first measurement after birth further significantly depended on gestational age at birth corrected for the postnatal age. This was found in all measured premature and mature neonates in a linear regression analysis. Furthermore, the longitudinal development in premature newborns showed an increase in PBR size, which we interpreted as gestational age dependent PBR changes. These changes were significant in group A, than reaching a steady plateau from 32 weeks of gestation and continued with higher PBR values compared to group B between 32nd and 36th gestational week. Also, linear regression analysis showed a significant dependence of PBR on postnatal age in the first four follow-up measurements. From these data a hypothesis was drawn, that the smaller GCX (bigger PBR) indicate a higher susceptibility with increased shedding of the fragile perinatal GCX in the extra-uterine environment compared to intra-uterine physiological maturation. Except for age, further possible influencing factors were tested, but none of the parameters showing a significant change over time as seen by comparing first measurement (FM) vs. last measurement (LM) correlated to PBR size at FM and LM. This could be due to small sample sizes, as general correlations could be detected when all measurements were included. The main limitations of the study were small sample size due to limited availability of stable very preterm babies, and related restrictions in follow-up measurements. Furthermore, PBR measurements only allow concluding on the size of the GXC without giving any information about its functionality. To affirm and strengthen the findings of the present study, further investigations are needed to improve our understanding of the pathophysiology of premature newborns.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 15. April 2021
• 1. Bericht­erstatter:in: Genzel-Boroviczény, Orsolya