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Faculty of Medical Sciences

Endothelial Activation during Cooling and Recovery in Patients with primary or secondary Raynaud's syndrome : A Feasibility/Pilot study

Moedt, M. (Martijn) (2016) Endothelial Activation during Cooling and Recovery in Patients with primary or secondary Raynaud's syndrome : A Feasibility/Pilot study. thesis, Medicine.

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Abstract

Raynaud’s phenomenon (RP) is an overreaction from the vascular system to cold stimuli, emotional triggers like stress and other causes. RP is common in the general population, especially in patients with rheumatic diseases. Currently, common believe is that RP occurs when the delicate balance that exists between vasodilatation and vasoconstriction of the small arterioles is shifted towards vasoconstriction. It leads to a characteristic sequential discoloration of the fingers and toes, usually starting with a white phase after the initial stimulus (ischaemia), followed by a blue phase (cyanotic), and finally a red phase (reactive hyperemia). In a large number of cases this color change is idiopathic, or primary. However, it may also be the initial event of an underlying disease. Although many conditions have been described that may result in RP, it is the hallmark of Systemic Sclerosis (SSc) in which it is commonly the first clinical symptom. The pathophysiological processes leading to microvascular abnormalities are not entirely clear. Systemic microvascular damage in SSc can be easily observed by Nailfold Capillary Microscopy (NCM). Possible pathophysiological contributors include endothelial injury as potential early or initiating mechanism and endothelial cell apoptosis, among others. Research concerning the pathophysiological changes in the blood vessels of individuals with RP during cooling is not abundant and studies addressing these issues by assessing biomarkers have shown mixed results, potentially because circulating plasma markers are measured at random, disregarding the fluctuations occurring with ischemia and reperfusion following a Raynaud’s attack which we think should be taken into account. Thus further research is required. The objective of this study is to assess the feasibility of measuring a time course in endothelial activation and oxidative stress markers in antecubital venous blood during cooling and recovery in patients Raynaud’s phenomenon, primary and secondary to SSc. This study is a pilot study designed to assess feasibility of this intended research. Also we aim to standardize our methods as much as possible with this pilot study. Three groups of patients were included: 3 with primary RP, 3 with secondary RP (secondary to SSc) and 5 healthy controls. In order to provoke a Raynaud’s attack, we performed a cooling experiment on them, following the standard protocol for that procedure. Blood was drawn at preset intervals: before cooling, at the lowest temperature reached during cooling, after 10 minutes recovery and after 20 minutes recovery. We assessed levels of lactate, LDH and CK in these samples. We found promising differences between the groups during cooling and recovery, but stated it is too soon to draw conclusions from that. We interpreted these results as a sign that were heading in the right direction, and with larger patient groups we might be able to prove significant differences. Because ultimately we’re actually interested in new biomarkers, we also think that the results we got with the biomarkers now show that our protocols and methods are viable and working, and that we could use those in the search for new and more experimental markers for endothelial activation and oxidative stress.

Item Type: Thesis (Thesis)
Supervisor name: Smit, Prof. dr. A.J. and Mulder, dr. D.J. and Vasculaire Geneeskunde and Universitair Medisch Centrum Groningen
Faculty: Medical Sciences
Date Deposited: 25 Jun 2020 11:03
Last Modified: 25 Jun 2020 11:03
URI: https://umcg.studenttheses.ub.rug.nl/id/eprint/2352

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