Van Roon, A. M., Abdulle, A. Eman, van Roon, A. M., Lefrandt, J. D., Smit, A.J., Bootsma, H., Fernandez, B.O., Minnion, M., Feelisch, M., van Goor, H. and Mulder, D.J. (2017) FRI0366 A pilot study on ischemia and reperfusion injury during a raynaud's attack: sequential assessment of redox stress parameters in a unique cooling and rewarming experiment. Annals of the Rheumatic Diseases, 76 (2), 625-626. (doi:10.1136/annrheumdis-2017-eular.5972).
Abstract
Background: Oxidative stress plays a role in systemic sclerosis (SSc), but the molecular mechanisms involved are incompletely understood. During an attack of Raynaud's phenomenon (RP) a period of ischemia (I), followed by reperfusion (R) occurs frequently, associated with the severity of vasculopathy. [1] Only in secondary RP digital ulcers develop. We hypothesized that I/R injury may play a role in the pathogenesis and could offer new therapeutic targets.
Objectives: To explore the course of oxidative stress in patients with SSc compared with primary RP and healthy controls.
Methods: A total of 30 patients were included: 10 with limited cutaneous SSc (age: 57 (53–61) yr, male/female 5/5), 10 with primary RP (age: 54 (41–58), 2/8), and 10 healthy controls (age: 25 (22–25), 3/7). A standardized cooling experiment was performed and digital perfusion was assessed in all 5 fingers using photo-electric plethysmography: at baseline (T=0) the dominant hand was submerged in water at 33°C, followed by cooling in steps of 3°C every 4 minutes, until 6°C or when pain became intolerable (T=1). Recording was continued 10 (T=2) and 30 (T=3) minutes of rewarming to ambient temperature (23°C). Blood was drawn from ipsilateral cubital vein at T0, 1, 2 and 3, markers for tissue injury (lactate, LDH, creatinine phosphokinase (CPK) [routine methods]), redox status (free thiols corrected for total protein) and nitric oxide (NO) activity (NO2–, NO3–, RXNO) were measured in plasma. [1–3] Numbers are in median (IQR).
Results: Baseline free thiols were significantly decreased in RP vs. controls (5.18 (4.79–5.63) vs 5.87 (5.41–5.99) umol/g, p=0.013), with no differences in lactate, LDH, CPK, and NO activity. Raynaud's attack was induced in all RP patients but not in controls. Median duration of hypoperfusion was greater in SSc vs. PRP (30 (27–35) vs. 12 (9–14) min, p=0.010), with a considerably longer recovery time (8 (4–10) vs. 0 (0–1) min, p=0.006). No changes were observed in lactate, LDH, and CPK levels. A rise in free thiols occurred at recovery (T4) in all 3 groups (figure 1). The concentrations of NO-related products did not change during cooling or recovery. No association was detected between the extent of I/R and plasma parameters.
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